WO2016145050A1

WO2016145050A1 - Microfluidic devices having flexible features and methods of making the same

Info

Publication number: WO2016145050A1
Application number: PCT/US2016/021519
Authority: WO
Inventors: Joseph M. Desimone; Jason P. Rolland
Original assignee: Carbon3D, Inc.
Priority date: 2015-03-10
Filing date: 2016-03-09
Publication date: 2016-09-15

Abstract

Provided herein are microfluidic devices having seamless channels with curved cross-section segments extending in a non-linear direction and/or having a tapering cross-section, wherein at least a portion of said device is flexible. Methods, systems and apparatus for the production of the same by three dimensional additive manufacturing is also provided.

Description

MICROFLUIDIC DEVICES HAVING FLEXIBLE FEATURES

AND METHODS OF MAKING THE SAME

Related Applications

This application claims the benefit of United States Provisional Patent Application Serial No. 62/130,791, filed March 10, 2015, the disclosure of which is incorporated by reference herein in its entirety.

Background of the Invention

Microfluidic devices show promise as small-scale liquid conduits finding various uses, such as flow modeling of capillary beds and "lab on a chip" devices in which chemical reactions may be performed. Such devices may be created with soft lithography, and more recently with 3D printing. See Gross et al., Anal. Chem. 86(7):3240-3253, 2014.

In each of these methods, the channels formed in the structure are often rectangular due to the layer-by-layer method of manufacturing. The presence of abrupt angles between adjacent walls (i.e., corners) in the microchannel cross-section can create high shear and/or complex turbulent fluid flow that could have deleterious effects on reaction chemistries and/or could damage microorganisms or cells in suspension. It could also lead to particle trapping and eventual plugging of the channel.

The formation of micron-sized channels having a smooth circular cross-section and created from a wider variety of materials remains a challenge.

One study recently reported forming a circular cross-section poly(dimethylsiloxane) microfluidics system to replicate cardiovascular flow conditions using soft lithography in which polymerization takes place around a gas stream. Fiddes et al., Biomaterials 31 :3459-3464, 2010. However, the method does not allow for incorporation of complex geometries into the fabrication.

U.S. Patent application publication 2010/0068740 to Kaplan et al. reported the use of an elongate rod to form cylindrical channels in a polymer solidified around it. However, damage to the structures upon removal of the rod may result, and the method appears restricted to linear channels.

There remains a need for alternative methods that can create microfluidic devices having curved cross-section segments and/or more complex structural features. Further, there remains a need to enable fabrication of such devices having flexible features. Summary of the Invention

Described herein are microfluidic devices as well as methods, systems and apparatus (including associated control methods, systems and apparatus), for the production of the same by additive manufacturing.

Provided herein according to some embodiments is a microfluidic device which includes

(a) a housing configured to accommodate a fluid therein, said housing comprising at least one seamless channel having a curved cross-section segment, wherein (i) at least a portion of said channel extends in a non-linear direction; and/or has a tapering cross-section, (ii) wherein at least a portion of said channel has an average diameter of from 0.1 to 1000 microns, and/or (iii) wherein at least a portion of said device is flexible; and (b) optionally, an actuator {e.g., a mechanical or electromechanical actuator) operably associated therewith.

In some embodiments, the housing comprises a semi-rigid or elastomeric material. In some embodiments, channel comprises a lobed, elliptical, semicircular or circular cross-section segment, or a combination thereof {e.g., a multi-lobed clover leaf cross-section segment). In some embodiments, the housing comprises at least two of said channels, optionally wherein at least two of said channels are in fluid connection with one another, and optionally wherein said housing comprises said channels in a density of 1-10,000 channels per square millimeter.

In some embodiments, the device comprises two or more planes of channels in the z- direction and the channels of said planes are in a crisscross or grid pattern with respect to each other. In some embodiments, the channels are configured to form a valve where they cross.

In some embodiments, the housing is configured to form a passive micromixer. In some embodiments, the housing is configured to form an active micromixer. In some embodiments, the device further comprises a microfluidic valve formed therein and configured to control the flow of fluid {e.g., liquid or gas) through said at least one channel. In some embodiments, the valve is flexible.

In some embodiments, the device further comprises a microfluidic pump configured to mix, meter, recirculate, or agitate a fluid in the housing. In some embodiments, the microfluidic pump is directly on or in said housing.

In some embodiments, the housing comprises a biodegradable or biocompatible material. In some embodiments, the one or more channels have an inner surface, said inner surface comprising a smooth wall.

In some embodiments, the housing further includes a chamber configured to or dimensioned to contain a fluid therein. In some embodiments, the chamber is in seamless fluid connection with one or more channels, wherein at least a portion of said chamber has an average diameter of from 0.1 to 1000 millimeters.

In some embodiments, the housing further includes one or more macro-to-micro interfaces therein {e.g., a port or inlet configured to accept a syringe, tube, etc.).

In some embodiments, the housing is unitary. In some embodiments, the housing is a unitary member.

In some embodiments, the housing is flexible. In some embodiments, the macro-to-micro interface(s) are flexible.

The present invention also provides a method of forming a microfluidic device or portion thereof as taught herein. In preferred (but not necessarily limiting) embodiments, the method is carried out continuously. In preferred (but not necessarily limiting) embodiments, the microfluidic device is produced from a liquid interface. Hence they are sometimes referred to, for convenience and not for purposes of limitation, as "continuous liquid interphase printing" or "continuous liquid interface production" ("CLIP") herein (the two being used interchangeably). See, e.g., J. Tumbleston et al., Continuous liquid interface production of 3D objects, Science 347, 1349-1352 (published online March 16, 2015). A schematic representation of one embodiment thereof is given in FIG. 1 herein.

In some embodiments, the method includes: (a) providing a carrier and an optically transparent member having a build surface, the carrier and the build surface defining a build region therebetween; (b) filling the build region with a polymerizable liquid; (c) irradiating the build region with light through the optically transparent member to form a solid polymer scaffold from the first component and advancing (e.g., advancing concurrently— that is, simultaneously, or sequentially in an alternating fashion with irradiating steps) the carrier away from the build surface to form the microfluidic device or portion thereof.

In some embodiments, the polymerizable liquid comprising a mixture of: (i) a light polymerizable liquid first component, and (ii) a second solidifiable component different from the first component. In some embodiments, the method includes: (a) providing a carrier and an optically transparent member having a build surface, the carrier and the build surface defining a build region therebetween; (b) filling the build region with a polymerizable liquid, the polymerizable liquid comprising a mixture of: (i) a light polymerizable liquid first component, and (ii) a second solidifiable component different from the first component, and optionally, (in) a dye, pigment or other material dispersed therein that blocks or absorbs light at the curing wavelength; (c) irradiating the build region with light through the optically transparent member to form a solid polymer scaffold from the first component and advancing (e.g., advancing concurrently— that is, simultaneously, or sequentially in an alternating fashion with irradiating steps) the carrier away from the build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, the microfluidic device and containing the second solidifiable component carried in the scaffold in unsolidified or uncured form; and (d) concurrently with or subsequent to the irradiating step, solidifying and/or curing the second solidifiable component in the three-dimensional intermediate to form the microfluidic device.

In some embodiments, the second component comprises: (i) a polymerizable liquid solubilized in or suspended in the first component; (ii) a polymerizable solid solubilized in the first component; or (Hi) a polymer solubilized in the first component. In other embodiments, the second component comprises: (i) a polymerizable solid suspended in the first component; or (ii) solid thermoplastic or thermoset polymer particles suspended in the first component.

In some embodiments, the first component comprises a blocked or reactive blocked prepolymer and (optionally but in some embodiments preferably) a reactive diluent, and the second component comprises a chain extender. The first components react together to form a blocked polymer scaffold during the irradiating step, which is unblocked by heating during the second step to in turn react with the chain extender.

In some embodiments, the microfluidic device or three-dimensional intermediate thereof is collapsible or compressible (e.g., elastic).

In some embodiments, the three-dimensional object comprises a polymer blend (e.g., an interpenetrating polymer network, a semi-interpenetrating polymer network, a sequential interpenetrating polymer network) formed from the first component and the second component.

In some embodiments, the polymerizable liquid comprises, in some embodiments: from 1, 2 or 5 percent by weight to 20, 30 or 40 percent by weight of the first component; and from 60, 70 or 80 percent by weight to 95, 98 or 99 percent by weight of the second component (optionally including one or more additional components). In other embodiments, the polymerizable liquid comprises from 1, 2 or 5 percent by weight to 20, 30 or 40 percent by weight of the second component; and from 60, 70 or 80 percent by weight to 95, 98 or 99 percent by weight of the first component (optionally including one or more additional components).

In some embodiments, the solidifying and/or curing step (d) is carried out concurrently with the irradiating step (c) and: (i) the solidifying and/or curing step is carried out by precipitation; (ii) the irradiating step generates heat from the polymerization of the first component in an amount sufficient to thermally solidify or polymerize the second component (e.g., to a temperature of 50 or 80 to 100 °C, for polymerizing polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)); and (Hi) the second component (e.g., a light or ultraviolet light curable epoxy resin) is solidified by the same light as is the first component in the irradiating step.

In some embodiments, the solidifying and/or curing step (d) is carried out subsequent to the irradiating step (c) and is carried out by: (i) heating the second solidifiable component; (ii) irradiating the second solidifiable component with light at a wavelength different from that of the light in the irradiating step (c); (in) contacting the second polymerizable component to water; or (iv) contacting the second polymerizable component to a catalyst.

In some embodiments, the second component comprises a polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), a silicone resin, or natural rubber, and the solidifying and/or curing step is carried out by heating.

In some embodiments, the second component comprises a cationically cured resin (e.g., an epoxy resin or a vinyl ether) and the solidifying and/or curing step is carried out irradiating the second solidifiable component with light at a wavelength different from that of the light in the irradiating step (c).

In some embodiments, the second component comprises a polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), and the solidifying and/or curing step is carried out by contacting the second component to water (e.g., in liquid, gas, or aerosol form).

In some embodiments, the second component comprises a polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), a silicone resin, a ring-opening metathesis polymerization resin, or a click chemistry resin (alkyne monomers in combination with compound plus an azide monomers), and the solidifying and/or curing step is carried out by contacting the second component to a polymerization catalyst (e.g., a metal catalyst such as a tin catalyst, and/or an amine catalyst, for polyurethane/polyurea resins; platinum or tin catalysts for silicone resins; ruthenium catalysts for ring-opening metathesis polymerization resins; copper catalyst for click chemistry resins; etc., which catalyst is contacted to the article as a liquid aerosol, by immersion, etc.)

In some embodiments, the irradiating step and/or advancing step is carried out while also concurrently:

(i) continuously maintaining a dead zone (or persistent liquid interface) of polymerizable liquid in contact with the build surface, and

(ii) continuously maintaining a gradient of polymerization zone between the dead zone and the solid polymer and in contact with each thereof, the gradient of polymerization zone comprising the first component in partially cured form. In some embodiments, the first component comprises a free radical polymerizable liquid and the inhibitor comprises oxygen; or the first component comprises an acid-catalyzed or cationically polymerizable liquid, and the inhibitor comprises a base.

In some embodiments, the gradient of polymerization zone and the dead zone together have a thickness of from 1 to 1000 microns.

In some embodiments, the gradient of polymerization zone is maintained for a time of at least 5, 10, 20 or 30 seconds, or at least 1 or 2 minutes.

In some embodiments, the advancing is carried out at a cumulative rate of at least 0.1, 1, 10, 100 or 1000 microns per second.

In some embodiments, the build surface is substantially fixed or stationary in the lateral and/or vertical dimensions.

In some embodiments the method further comprises vertically reciprocating the carrier with respect to the build surface to enhance or speed the refilling of the build region with the polymerizable liquid.

In some embodiments, the microfluidic device comprises a macro-to-micro interface therein (e.g., a port or inlet configured to accept a syringe, tube, etc.) and the microfluidic device comprising said macro-to-micro interface is formed as one piece.

A further aspect of the invention is a polymerizable liquid substantially as described herein above and below, and/or for use in carrying out a method of any preceding claim.

Non-limiting examples and specific embodiments of the present invention are explained in greater detail in the drawings herein and the specification set forth below. The disclosure of all United States Patent references cited herein are to be incorporated herein by reference in their entirety.

Brief Description of the Drawings

FIG. 1 is a schematic illustration of one embodiment of a three dimensional printing method that may be used to form microfluidic devices (3D object) of the present invention.

FIG. 2 is a perspective view of one embodiment of an apparatus that may be used in the present invention.

FIGS. 3 to 5 are flow charts illustrating control systems and methods that may be used for carrying out methods of the present invention.

FIG. 6 is a graphic illustration of a process of the invention indicating the position of the carrier in relation to the build surface or plate, where both advancing of the carrier and irradiation of the build region is carried out continuously. Advancing of the carrier is illustrated on the vertical axis, and time is illustrated on the horizontal axis. FIG. 7 is a graphic illustration of another process of the invention indicating the position of the carrier in relation to the build surface or plate, where both advancing of the carrier and irradiation of the build region is carried out stepwise, yet the dead zone and gradient of polymerization are maintained. Advancing of the carrier is again illustrated on the vertical axis, and time is illustrated on the horizontal axis.

FIG. 8 is a graphic illustration of another process which may be used in the invention indicating the position of the carrier in relation to the build surface or plate, where both advancing of the carrier and irradiation of the build region is carried out stepwise, the dead zone and gradient of polymerization are maintained, and a reciprocating step is introduced between irradiation steps to enhance the flow of polymerizable liquid into the build region. Advancing of the carrier is again illustrated on the vertical axis, and time is illustrated on the horizontal axis.

FIG. 9 is a detailed illustration of a reciprocation step of FIG. 8, showing a period of acceleration occurring during the upstroke (i.e., a gradual start of the upstroke) and a period of deceleration occurring during the downstroke (i.e., a gradual end to the downstroke).

FIG. 10A depicts a dual cure system employing a thermally cleavable end group. I.

Crosslinked blocked diisocyanate prepolymer containing unreacted chain extender. II. Polymer blend of: i) linear ethylenically unsaturated blocking monomer copolymerized with reactive diluent and ii) linear thermoplastic polyurethane.

FIG. 10B depicts a method of the present invention carried out with (meth)acrylate blocked diisocyanates (ABDIs). I. Crosslinked blocked diisocyanate containing unreacted soft segment and chain extender. II. Polymer blend of: i) linear ethylenically unsaturated blocking monomer copolymerized with reactive diluent and ii) linear thermoplastic polyurethane.

FIG. IOC depicts a method of the present invention carried out with (meth)acrylate blocked chain extenders (ABCEs). I. Crosslinked blocked diisocyanate containing chain extender containing unreacted soft segment and chain extender. II. Polymer blend of: i) linear ethylenically unsaturated blocking monomer copolymerized with reactive diluent and ii) linear thermoplastic polyurethane.

FIG. 11 is a schematic of a microfluidic device according to some embodiments of the present invention. Note that the parts are not shown to scale.

FIG. 12 is a schematic showing example cross-sections 25 of channels 20 in a microfluidic device according to some embodiments, with circular (A), elliptical (B), semicircular (C) and lobed (D, with four lobes) shown. FIG. 13 is a schematic of a microfluidic device with a housing 10 having channels 20 smoothly branching and reconnecting, akin to a capillary bed. A pump 40 is provided to pump fluid through the channels.

FIG. 14 is a schematic showing a microfluidic device with a housing 10 having a tapering inlet into a helical channel 20.

FIG. 15 is a schematic slice of a channel 20 showing rounded protrusions or columns 61 therein to provide a passive micromixer 60 which can mix the fluid as it travels through the channel 20.

FIG. 16 provides a schematic of a microfluidic device according to some embodiments that has a flexible housing 10. In this example embodiment, the housing 10 has two or more planes of said channels 20 in the z-direction, and the channels of said planes are in a crisscross or grid pattern with respect to each other. The channels are configured to form a valve 50 where they cross by having a flexible layer between the channels at the cross point, which can bend to limit flow through one channel when fluid is provided in the other channel positioned over or under it.

FIG. 17 provides a schematic of a microfluidic device according to some embodiments having an integrated macro-to-micro interface 70 on a chamber 30. In this embodiment, the interface provides a unitary port as part of the device for a syringe to connect.

Detailed Description of Illustrative Embodiments

The present invention is now described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather these embodiments are provided so that this disclosure will be thorough and complete and will fully convey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, the thickness or size of certain lines, layers, components, elements or features may be exaggerated for clarity. Where used, broken lines illustrate optional features or operations unless specified otherwise.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a," "an" and "the" are intended to include plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements components and/or groups or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or groups or combinations thereof.

As used herein, the term "and/or" includes any and all possible combinations or one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or").

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and claims and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Well-known functions or constructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being "on," "attached" to, "connected" to, "coupled" with, "contacting," etc., another element, it can be directly on, attached to, connected to, coupled with and/or contacting the other element or intervening elements can also be present. In contrast, when an element is referred to as being, for example, "directly on," "directly attached" to, "directly connected" to, "directly coupled" with or "directly contacting" another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed "adjacent" another feature can have portions that overlap or underlie the adjacent feature.

Spatially relative terms, such as "under," "below," "lower," "over," "upper" and the like, may be used herein for ease of description to describe an element's or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, elements described as "under" or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus the exemplary term "under" can encompass both an orientation of over and under. The device may otherwise be oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms "upwardly," "downwardly," "vertical," "horizontal" and the like are used herein for the purpose of explanation only, unless specifically indicated otherwise.

It will be understood that, although the terms first, second, etc., may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. Rather, these terms are only used to distinguish one element, component, region, layer and/or section, from another element, component, region, layer and/or section. Thus, a first element, component, region, layer or section discussed herein could be termed a second element, component, region, layer or section without departing from the teachings of the present invention. The sequence of operations (or steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.

In general, the microfmidic devices of the present invention may be formed using top- down or bottom-up three dimensional fabrication. In general, top-down three-dimensional dual cure fabrication is carried out by:

(a) providing a polymerizable liquid reservoir having a polymerizable liquid fill level and a carrier positioned in the reservoir, the carrier and the fill level defining a build region therebetween;

(b) filling the build region with a polymerizable liquid (i.e., the resin), said polymerizable liquid comprising a mixture of (i) a light (typically ultraviolet light) polymerizable liquid first component, and (ii) a second solidifiable component of the dual cure system; and then

(c) irradiating the build region with light to form a solid polymer scaffold from the first component and also advancing (typically lowering) the carrier away from the build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, the three-dimensional object and containing said second solidifiable component (e.g., a second reactive component) carried in the scaffold in unsolidified and/or uncured form.

A wiper blade, doctor blade, or optically transparent (rigid or flexible) window, may optionally be provided at the fill level to facilitate leveling of the polymerizable liquid, in accordance with known techniques. In the case of an optically transparent window, the window provides a build surface against which the three dimensional intermediate is formed, analogous to the build surface in bottom-up three dimensional fabrication as discussed below.

In general, bottom-up three dimensional dual cure fabrication is carried out by:

(a) providing a carrier and an optically transparent member having a build surface, the carrier and the build surface defining a build region therebetween;

(c) irradiating the build region with light through said optically transparent member to form a solid polymer scaffold from the first component and also advancing (typically raising) the carrier away from the build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, the three-dimensional object and containing said second solidifiable component (e.g., a second reactive component) carried in the scaffold in unsolidified and/or uncured form.

In some embodiments of bottom up or top down three dimensional fabrication as implemented in the context of the present invention, the build surface is stationary during the formation of the device or portion thereof; in other embodiments of bottom-up three dimensional fabrication as implemented in the context of the present invention, the build surface is tilted, slid, flexed and/or peeled, and/or otherwise translocated or released from the growing three dimensional device or portion thereof, usually repeatedly, during formation.

In some embodiments of bottom up or top down three dimensional fabrication as carried out in the context of the present invention, the polymerizable liquid (or resin) is maintained in liquid contact with both the growing three dimensional device or portion thereof and the build surface during both the filling and irradiating steps, during fabrication of some of, a major portion of, or all of the three dimensional device or portion thereof.

In some embodiments of bottom-up or top down three dimensional fabrication as carried out in the context of the present invention, the growing three dimensional device or portion thereof is fabricated in a layerless manner (e.g., through multiple exposures or "slices" of patterned actinic radiation or light) during at least a portion of the formation of the three dimensional device or portion thereof.

In some embodiments of bottom up or top down three dimensional fabrication as carried out in the context of the present invention, the growing three dimensional device or portion thereof is fabricated in a layer-by-layer manner (e.g., through multiple exposures or "slices" of patterned actinic radiation or light), during at least a portion of the formation of the three dimensional device or portion thereof.

In some embodiments of bottom up or top down three dimensional fabrication employing a rigid or flexible optically transparent window, a lubricant or immiscible liquid may be provided between the window and the polymerizable liquid (e.g., a fluorinated fluid or oil such as a perfluoropolyether oil).

From the foregoing it will be appreciated that, in some embodiments of bottom-up or top down three dimensional fabrication as carried out in the context of the present invention, the growing three dimensional device or portion thereof is fabricated in a layerless manner, and that same growing three dimensional device or portion thereof is fabricated in a layer-by-layer manner during the formation of at least one other portion thereof. Thus, operating mode may be changed once, or on multiple occasions, between layerless fabrication and layer-by-layer fabrication, as desired by operating conditions such as part geometry.

In preferred embodiments, the microfluidic device or portion thereof is formed by continuous liquid interface production (CLIP). CLIP is known and described in, for example, PCT Applications Nos. PCT/US2014/015486 (published as US Patent No. 9,211,678 on December 15, 2015); PCT/US2014/015506 (also published as US Patent No. 9,205,601 on December 8, 2015), PCT/US2014/015497 (also published as US Patent No 9,216,546 on Dec. 22, 2015), and in J. Tumbleston, D. Shirvanyants, N. Ermoshkin et al, Continuous liquid interface production of 3D Objects, Science 347, 1349-1352 (published online 16 March 2015). In some embodiments, CLIP employs features of a bottom-up three dimensional fabrication, but the irradiating and/or advancing steps are carried out while also concurrently maintaining a stable or persistent liquid interface between the growing object and the build surface or window, such as by: (i) continuously maintaining a dead zone of polymerizable liquid in contact with said build surface, and (ii) continuously maintaining a gradient of polymerization zone (such as an active surface) between the dead zone and the solid polymer and in contact with each thereof, the gradient of polymerization zone comprising the first component in partially cured form. In some embodiments of CLIP, the optically transparent member comprises a semipermeable member (e.g., a fluoropolymer), and the continuously maintaining a dead zone is carried out by feeding an inhibitor of polymerization through the optically transparent member, thereby creating a gradient of inhibitor in the dead zone and optionally in at least a portion of the gradient of polymerization zone.

In some embodiments, the stable liquid interface may be achieved by other techniques, such as by providing an immiscible liquid as the build surface between the polymerizable liquid and the optically transparent member, by feeding a lubricant to the build surface (e.g., through an optically transparent member which is semipermeable thereto, and/or serves as a reservoir thereof), etc.

"Shape to be imparted to" refers to the case where the shape of the intermediate object slightly changes between formation thereof and forming the subsequent three-dimensional product such as a microfluidic device or portion thereof, typically by shrinkage (e.g., up to 1, 2 or 4 percent by volume), expansion (e.g., up to 1, 2 or 4 percent by volume), removal of support structures, or by intervening forming steps (e.g., intentional bending, stretching, drilling, grinding, cutting, polishing, or other intentional forming after formation of the intermediate product, but before formation of the subsequent three-dimensional product). "Hydrocarbyl" as used herein refers to a bifunctional hydrocarbon group, which hydrocarbon may be aliphatic, aromatic, or mixed aliphatic and aromatic, and optionally containing one or more (e.g., 1, 2, 3, or 4) heteroatoms (typically selected from N, O, and S). Such hydrocarbyl groups may be optionally substituted and may contain from 1, 2, or 3 carbon atoms, up to 6, 8 or 10 carbon atoms or more, and up to 40, 80, or 100 carbon atoms or more.

1. Polymerizable liquids.

Any suitable polymerizable liquid can be used to enable the present invention. In some embodiments, the polymerizable liquid comprises, in addition to a first component (or "part A") such as described in this section, a second component (or "part B") such as described in the "Dual Hardening" section below. The liquid (sometimes also referred to as "liquid resin" "ink," or simply "resin" herein) can include a monomer, particularly photopolymerizable and/or free radical polymerizable monomers, and a suitable initiator such as a free radical initiator, and combinations thereof. Examples include, but are not limited to, acrylics, methacrylics, acrylamides, styrenics, olefins, halogenated olefins, cyclic alkenes, maleic anhydride, alkenes, alkynes, carbon monoxide, functionalized oligomers, multifunctional cute site monomers, functionalized PEGs, etc., including combinations thereof. Examples of liquid resins, monomers and initiators include but are not limited to those set forth in US Patent Nos. 8,232,043; 8,1 19,214; 7,935,476; 7,767,728; 7,649,029; PCT publication WO 2012129968 Al ; and CN 102715751 A; JP 2012210408 A.

In some embodiments of the methods and compositions described above and below, the polymerizable liquid has a viscosity of 500 or 1,000 centipoise or more at room temperature and/or under the operating conditions of the method, up to a viscosity of 10,000, 20,000, or 50,000 centipoise or more, at room temperature and/or under the operating conditions of the method.

Acid catalyzed polymerizable liquids. While in some embodiments as noted above the polymerizable liquid comprises a free radical polymerizable liquid (in which case an inhibitor may be oxygen), in other embodiments the polymerizable liquid comprises an acid catalyzed, or cationically polymerized, polymerizable liquid. In such embodiments the polymerizable liquid comprises monomers that contain groups suitable for acid catalysis, such as epoxide groups, vinyl ether groups, etc. Thus suitable monomers include olefins such as methoxyethene, 4- methoxystyrene, styrene, 2-methylprop-l-ene, 1,3 -butadiene, etc.; heterocyclic monomers (including lactones, lactams, and cyclic amines) such as oxirane, thietane, tetrahydrofuran, oxazoline, 1,3, dioxepane, oxetan-2-one, etc., and combinations thereof. A suitable (generally ionic or non-ionic) photoacid generator (PAG) is included in the acid catalyzed polymerizable liquid, examples of which include, but are not limited to onium salts, sulfonium and iodonium salts, etc., such as diphenyl iodide hexafluorophosphate, diphenyl iodide hexafluoroarsenate, diphenyl iodide hexafluoroantimonate, diphenyl p-methoxyphenyl triflate, diphenyl p-toluenyl triflate, diphenyl p-isobutylphenyl triflate, diphenyl p-tert-butylphenyl triflate, triphenylsulfonium hexafluororphosphate, triphenylsulfonium hexafluoroarsenate, triphenylsulfonium hexafluoroantimonate, triphenylsulfonium triflate, dibutylnaphthylsulfonium triflate, etc., including mixtures thereof. See, e.g., US Patent Nos. 7,824,839; 7,550,246; 7,534,844; 6,692,891 ; 5,374,500; and 5,017,461; see also Photoacid Generator Selection Guide or the electronics industry and energy curable coatings (BASF 2010).

Hydrogels. In some embodiments suitable resins includes photocurable hydrogels like poly(ethylene glycols) (PEG) and gelatins. PEG hydrogels have been used to deliver a variety of biologicals, including growth factors; however, a great challenge facing PEG hydrogels crosslinked by chain growth polymerizations is the potential for irreversible protein damage. Conditions to maximize release of the biologicals from photopolymerized PEG diacrylate hydrogels can be enhanced by inclusion of affinity binding peptide sequences in the monomer resin solutions, prior to photopolymerization allowing sustained delivery. Gelatin is a biopolymer frequently used in food, cosmetic, pharmaceutical and photographic industries. It is obtained by thermal denaturation or chemical and physical degradation of collagen. There are three kinds of gelatin, including those found in animals, fish and humans. Gelatin from the skin of cold water fish is considered safe to use in pharmaceutical applications. UV or visible light can be used to crosslink appropriately modified gelatin. Methods for crosslinking gelatin include cure derivatives from dyes such as Rose Bengal.

Photocurable silicone resins. A suitable resin includes photocurable silicones. UV cure silicone rubber, such as Siliopren™ UV Cure Silicone Rubber can be used as can LOCTITE™ Cure Silicone adhesives sealants.

Biodegradable resins. Biodegradable resins are particularly important for implantable devices to deliver drugs or for temporary performance applications, like biodegradable screws and stents (US Patent Nos. 7,919,162; 6,932,930). Biodegradable copolymers of lactic acid and glycolic acid (PLGA) can be dissolved in PEG dimethacrylate to yield a transparent resin suitable for use. Polycaprolactone and PLGA oligomers can be functionalized with acrylic or methacrylic groups to allow them to be effective resins for use.

Photocurable polyurethanes. A particularly useful resin is photocurable polyurethanes, including polyureas, and copolymers of polyurethanes and polyureas (e.g., poly(urethane-urea). A photopolymerizable polyurethane/polyurea composition comprising (1) a polyurethane based on an aliphatic diisocyanate, poly(hexamethylene isophthalate glycol) and, optionally, 1,4- butanediol; (2) a polyfunctional acrylic ester; (3) a photoinitiator; and (4) an anti-oxidant, can be formulated so that it provides a hard, abrasion-resistant, and stain-resistant material (US Patent 4,337,130). Photocurable thermoplastic polyurethane elastomers incorporate photoreactive diacetylene diols as chain extenders.

High performance resins. In some embodiments, high performance resins are used. Such high performance resins may sometimes require the use of heating to melt and/or reduce the viscosity thereof. Examples of such resins include, but are not limited to, resins for those materials sometimes referred to as liquid crystalline polymers of esters, ester-imide, and ester- amide oligomers, as described in US Patent Nos. 7,507,784; 6,939,940. Since such resins are sometimes employed as high-temperature thermoset resins, in the present invention they further comprise a suitable photoinitiator such as benzophenone, anthraquinone, amd fluoroenone initiators (including derivatives thereof), to initiate cross-linking on irradiation, as discussed further below.

Additional example resins. Particularly useful resins for dental applications include

EnvisionTEC's Clear Guide, EnvisionTEC's E-Denstone Material. Particularly useful resins for hearing aid industries include EnvisionTEC's e-Shell 300 Series of resins. Particularly useful resins include EnvisionTEC's HTM140IV High Temperature Mold Material for use directly with vulcanized rubber in molding / casting applications. A particularly useful material for making tough and stiff parts includes EnvisionTEC's RC31 resin. Particularly useful resin for investment casting applications include EnvisionTEC's Easy Cast EC500 resin and MadeSolid FireCast resin.

Additional resin ingredients. The liquid resin or polymerizable material can have solid particles suspended or dispersed therein. Any suitable solid particle can be used, depending upon the end product being fabricated. The particles can be metallic, organic/polymeric, inorganic, or composites or mixtures thereof. The particles can be nonconductive, semi-conductive, or conductive (including metallic and non-metallic or polymer conductors); and the particles can be magnetic, ferromagnetic, paramagnetic, or nonmagnetic. The particles can be of any suitable shape, including spherical, elliptical, cylindrical, etc. The particles can be of any suitable size (for example, ranging from 1 nm to 20 μηι average diameter).

The particles can comprise an active agent or detectable compound as described below, though these may also be provided dissolved solubilized in the liquid resin as also discussed below. For example, magnetic or paramagnetic particles or nanoparticles can be employed. The liquid resin can have additional ingredients solubilized therein, including pigments, dyes, active compounds or pharmaceutical compounds, detectable compounds (e.g., fluorescent, phosphorescent, radioactive), etc., again depending upon the particular purpose of the product being fabricated. Examples of such additional ingredients include, but are not limited to, proteins (e.g., antibodies), peptides, nucleic acids (DNA, RNA) such as siRNA, sugars, small organic compounds (drugs and drug-like compounds), etc., including combinations thereof.

Inhibitors of polymerization. Inhibitors or polymerization inhibitors for use in the present invention may be in the form of a liquid or a gas. In some embodiments, gas inhibitors are preferred. In some embodiments, liquid inhibitors such as oils or lubricants may be employed. In further embodiments, gas inhibitors which are dissolved in liquids (e.g., oils or lubricants) may be employed. For example, oxygen dissolved in a fiuorinated fluid. The specific inhibitor will depend upon the monomer being polymerized and the polymerization reaction. For free radical polymerization monomers, the inhibitor can conveniently be oxygen, which can be provided in the form of a gas such as air, a gas enriched in oxygen (optionally but in some embodiments preferably containing additional inert gases to reduce combustibility thereof), or in some embodiments pure oxygen gas. In alternate embodiments, such as where the monomer is polymerized by photoacid generator initiator, the inhibitor can be a base such as ammonia, trace amines (e.g. methyl amine, ethyl amine, di and trialkyl amines such as dimethyl amine, diethyl amine, trimethyl amine, triethyl amine, etc.), or carbon dioxide, including mixtures or combinations thereof.

Polymerizable liquids carrying live cells. In some embodiments, the polymerizable liquid may carry live cells as "particles" therein. Such polymerizable liquids are generally aqueous, and may be oxygenated, and may be considered as "emulsions" where the live cells are the discrete phase. Suitable live cells may be plant cells (e.g., monocot, dicot), animal cells (e.g., mammalian, avian, amphibian, reptile cells), microbial cells (e.g., prokaryote, eukaryote, protozoal, etc.), etc. The cells may be of differentiated cells from or corresponding to any type of tissue (e.g., blood, cartilage, bone, muscle, endocrine gland, exocrine gland, epithelial, endothelial, etc.), or may be undifferentiated cells such as stem cells or progenitor cells. In such embodiments the polymerizable liquid can be one that forms a hydrogel, including but not limited to those described in US Patent Nos. 7,651,683; 7,651,682; 7,556,490; 6,602,975; 5,836,313; etc.

2. Apparatus.

A non-limiting embodiment of an apparatus that may be used to form the microfluidic device or portion thereof is shown in FIG. 2. It comprises a radiation source 110 such as a digital light processor (DLP) providing electromagnetic radiation 120 which though reflective mirror 130 illuminates a build chamber defined by wall 140 and a rigid build plate 150 forming the bottom of the build chamber, which build chamber is filled with liquid resin 160. The bottom of the chamber 150 is constructed of rigid build plate comprising a rigid semipermeable member. The top of the object under construction 170 is attached to a carrier 180. The carrier is driven in the vertical direction by linear stage 190, although alternate structures can be used. These elements may be operably connected by suitable supports (200, 210, 220, 230).

A liquid resin reservoir, tubing, pumps, liquid level sensors and/or valves can be included to replenish the pool of liquid resin in the build chamber (not shown for clarity), though in some embodiments a simple gravity feed may be employed. Drives/actuators for the carrier or linear stage, along with associated wiring, can be included in accordance with known techniques (again not shown for clarity). The drives/actuators, radiation source, and in some embodiments pumps and liquid level sensors can all be operatively associated with a suitable controller, again in accordance with known techniques.

Build plates 150 used to carry out the present invention generally comprise or consist of a

(typically rigid or solid, stationary, and/or fixed) semipermeable (or gas permeable) member, alone or in combination with one or more additional supporting substrates (e.g., clamps and tensioning members to rigidify an otherwise flexible semipermeable material). The rigid semipermeable member can be made of any suitable material that is optically transparent at the relevant wavelengths (or otherwise transparent to the radiation source, whether or not it is visually transparent as perceived by the human eye— i.e., an optically transparent window may in some embodiments be visually opaque), including but not limited to porous or microporous glass, and the rigid gas permeable polymers used for the manufacture of rigid gas permeable contact lenses. See, e.g., Norman G. Gaylord, US Patent No. RE31,406; see also US Patent Nos. 7,862,176; 7,344,731; 7,097,302; 5,349,394; 5,310,571 ; 5,162,469; 5,141,665; 5,070,170; 4,923,906; and 4,845,089. In some embodiments such materials are characterized as glassy and/or amorphous polymers and/or substantially crosslinked that they are essentially non- swellable. Preferably the rigid semipermeable member is formed of a material that does not swell when contacted to the liquid resin or material to be polymerized (i.e., is "non-swellable").

Suitable materials for the rigid semipermeable member include rigid amorphous fluoropolymers, such as those described in US Patent Nos. 5,308,685 and 5,051,115. For example, such fluoropolymers are particularly useful over silicones that would potentially swell when used in conjunction with organic liquid resin inks to be polymerized. For some liquid resin inks, such as more aqueous-based monomeric systems and / or some polymeric resin ink systems that have low swelling tendencies, silicone based window materials maybe suitable. The solubility or permeability of organic liquid resin inks can be dramatically decreased by a number of known parameters including increasing the crosslink density of the window material or increasing the molecular weight of the liquid resin ink. In some embodiments the build plate may be formed from a thin film or sheet of material which is flexible when separated from the apparatus of the invention, but which is clamped and tensioned when installed in the apparatus (e.g., with a tensioning ring) so that it is rendered rigid in the apparatus. Particular materials include TEFLON AF® fluoropolymers, commercially available from DuPont. Additional materials include perfluoropolyether polymers such as described in US Patent Nos. 8,268,446; 8,263,129; 8,158,728; and 7,435,495.

It will be appreciated that essentially all solid materials, and most of those described above, have some inherent "flex" even though they may be considered "rigid," depending on factors such as the shape and thickness thereof and environmental factors such as the pressure and temperature to which they are subjected. In addition, the terms "stationary" or "fixed" with respect to the build plate is intended to mean that no mechanical interruption of the process occurs, or no mechanism or structure for mechanical interruption of the process (as in a layer-by- layer method or apparatus) is provided, even if a mechanism for incremental adjustment of the build plate (for example, adjustment that does not lead to or cause collapse of the gradient of polymerization zone) is provided.

The semipermeable member typically comprises a top surface portion, a bottom surface portion, and an edge surface portion. The build surface is on the top surface portion; and the feed surface may be on one, two, or all three of the top surface portion, the bottom surface portion, and/or the edge surface portion. In the embodiment illustrated in FIG. 2 the feed surface is on the bottom surface portion, but alternate configurations where the feed surface is provided on an edge, and/or on the top surface portion (close to but separate or spaced away from the build surface) can be implemented with routine skill.

The semipermeable member has, in some embodiments, a thickness of from 0.01, 0.1 or 1 millimeters to 10 or 100 millimeters, or more, depending upon the size of the item being fabricated, whether or not it is laminated to or in contact with an additional supporting plate such as glass, etc., as discussed further below.

The permeability of the semipermeable member to the polymerization inhibitor will depend upon conditions such as the pressure of the atmosphere and/or inhibitor, the choice of inhibitor, the rate or speed of fabrication, etc. In general, when the inhibitor is oxygen, the permeability of the semipermeable member to oxygen may be from 10 or 20 Barrers, up to 1000 or 2000 Barrers, or more. For example, a semipermeable member with a permeability of 10 Barrers used with a pure oxygen, or highly enriched oxygen, atmosphere under a pressure of 150 PSI may perform substantially the same as a semipermeable member with a permeability of 500 Barrers when the oxygen is supplied from the ambient atmosphere under atmospheric conditions.

Thus, the semipermeable member may comprise a flexible polymer film (having any suitable thickness, e.g., from 0.001, 0.01, 0.05, 0.1 or 1 millimeters to 1, 5, 10, or 100 millimeters, or more), and the build plate may further comprise a tensioning member (e.g., a peripheral clamp and an operatively associated strain member or stretching member, as in a "drum head"; a plurality of peripheral clamps, etc., including combinations thereof) connected to the polymer film and to fix and rigidify the film (e.g., at least sufficiently so that the film does not stick to the object as the object is advanced and resiliently or elastically rebound therefrom). The film has a top surface and a bottom surface, with the build surface on the top surface and the feed surface preferably on the bottom surface. In other embodiments, the semipermeable member comprises: (i) a polymer film layer (having any suitable thickness, e.g., from 0.001, 0.01, 0.1 or 1 millimeters to 5, 10 or 100 millimeters, or more), having a top surface positioned for contacting said polymerizable liquid and a bottom surface, and (ii) a rigid, gas permeable, optically transparent supporting member (having any suitable thickness, e.g., from 0.01, 0.1 or 1 millimeters to 10, 100, or 200 millimeters, or more), contacting said film layer bottom surface. The supporting member has a top surface contacting the film layer bottom surface, and the supporting member has a bottom surface which may serve as the feed surface for the polymerization inhibitor. Any suitable materials that are semipermeable (that is, permeable to the polymerization inhibitor) may be used. For example, the polymer film or polymer film layer may, for example, be a fluoropolymer film, such as an amorphous thermoplastic fluoropolymer like TEFLON AF 1600™ or TEFLON AF 2400™ fluoropolymer films, or perfluoropolyether (PFPE), particularly a crosslinked PFPE film, or a crosslinked silicone polymer film. The supporting member comprises a silicone or crosslinked silicone polymer member such as a polydimethylsiloxane polydmiethylxiloxane member, a rigid gas permeable polymer member, or a porous or microporous glass member. Films can be laminated or clamped directly to the rigid supporting member without adhesive (e.g., using PFPE and PDMS materials), or silane coupling agents that react with the upper surface of a PDMS layer can be utilized to adhere to the first polymer film layer. UV-curable, acrylate-functional silicones can also be used as a tie layer between UV-curable PFPEs and rigid PDMS supporting layers.

When configured for placement in the apparatus, the carrier defines a "build region" on the build surface, within the total area of the build surface. Because lateral "throw" (e.g., in the X and/or Y directions) is not required in the present invention to break adhesion between successive layers, as in the Joyce and Chen devices noted previously, the area of the build region within the build surface may be maximized (or conversely, the area of the build surface not devoted to the build region may be minimized). Hence in some embodiments, the total surface area of the build region can occupy at least fifty, sixty, seventy, eighty, or ninety percent of the total surface area of the build surface.

As shown in FIG. 2, the various components are mounted on a support or frame assembly 200. While the particular design of the support or frame assembly is not critical and can assume numerous configurations, in the illustrated embodiment it is comprised of a base 210 to which the radiation source 110 is securely or rigidly attached, a vertical member 220 to which the linear stage is operatively associated, and a horizontal table 230 to which wall 140 is removably or securely attached (or on which the wall is placed), and with the build plate rigidly fixed, either permanently or removably, to form the build chamber as described above.

As noted above, the build plate can consist of a single unitary and integral piece of a rigid semipermeable member, or can comprise additional materials. For example, a porous or microporous glass can be laminated or fixed to a rigid semipermeable material. Or, a semipermeable member as an upper portion can be fixed to a transparent lower member having purging channels formed therein for feeding gas carrying the polymerization inhibitor to the semipermeable member (through which it passes to the build surface to facilitate the formation of a release layer of unpolymerized liquid material, as noted above and below). Such purge channels may extend fully or partially through the base plate: For example, the purge channels may extend partially into the base plate, but then end in the region directly underlying the build surface to avoid introduction of distortion. Specific geometries will depend upon whether the feed surface for the inhibitor into the semipermeable member is located on the same side or opposite side as the build surface, on an edge portion thereof, or a combination of several thereof.

Any suitable radiation source (or combination of sources) can be used, depending upon the particular resin employed, including electron beam and ionizing radiation sources. In a preferred embodiment the radiation source is an actinic radiation source, such as one or more light sources, and in particular one or more ultraviolet light sources. Any suitable light source can be used, such as incandescent lights, fluorescent lights, phosphorescent or luminescent lights, a laser, light-emitting diode, etc., including arrays thereof. The light source preferably includes a pattern-forming element operatively associated with a controller, as noted above. In some embodiments, the light source or pattern forming element comprises a digital (or deformable) micromirror device (DMD) with digital light processing (DLP), a spatial modulator (SLM), or a microelectromechanical system (MEMS) mirror array, a mask (aka a reticle), a silhouette, or a combination thereof. See US Patent No. 7,902,526. Preferably the light source comprises a spatial light modulation array such as a liquid crystal light valve array or micromirror array or DMD {e.g., with an operatively associated digital light processor, typically in turn under the control of a suitable controller), configured to carry out exposure or irradiation of the polymerizable liquid without a mask, e.g., by maskless photolithography. See, e.g., US Patent Nos. 6,312,134; 6,248,509; 6,238,852; and 5,691,541.

In some embodiments, there may be movement in the X and/or Y directions concurrently with movement in the Z direction, with the movement in the X and/or Y direction hence occurring during polymerization of the polymerizable liquid (this is in contrast to the movement described in Y. Chen et al., or M. Joyce, supra, which is movement between prior and subsequent polymerization steps for the purpose of replenishing polymerizable liquid). In the present invention such movement may be carried out for purposes such as reducing "burn in" or fouling in a particular zone of the build surface.

Because an advantage of some embodiments of the present invention is that the size of the build surface on the semipermeable member (i.e., the build plate or window) may be reduced due to the absence of a requirement for extensive lateral "throw" as in the Joyce or Chen devices noted above, in the methods, systems and apparatus of the present invention lateral movement (including movement in the X and/or Y direction or combination thereof) of the carrier and object (if such lateral movement is present) is preferably not more than, or less than, 80, 70, 60, 50, 40, 30, 20, or even 10 percent of the width (in the direction of that lateral movement) of the build region.

While in some embodiments the carrier is mounted on an elevator to advance up and away from a stationary build plate, on other embodiments the converse arrangement may be used: That is, the carrier may be fixed and the build plate lowered to thereby advance the carrier away therefrom. Numerous different mechanical configurations will be apparent to those skilled in the art to achieve the same result.

Depending on the choice of material from which the carrier is fabricated, and the choice of polymer or resin from which the article is made, adhesion of the article to the carrier may sometimes be insufficient to retain the article on the carrier through to completion of the finished article or "build." For example, an aluminum carrier may have lower adhesion than a poly(vinyl chloride) (or "PVC") carrier. Hence one solution is to employ a carrier comprising a PVC on the surface to which the article being fabricated is polymerized. If this promotes too great an adhesion to conveniently separate the finished part from the carrier, then any of a variety of techniques can be used to further secure the article to a less adhesive carrier, including but not limited to the application of adhesive tape such as "Greener Masking Tape for Basic Painting #2025 High adhesion" to further secure the article to the carrier during fabrication.

3. Controller and process control.

The methods and apparatus of the invention can include process steps and apparatus features to implement process control, including feedback and feed-forward control, to, for example, enhance the speed and/or reliability of the method.

A controller for use in carrying out the present invention may be implemented as hardware circuitry, software, or a combination thereof. In one embodiment, the controller is a general purpose computer that runs software, operatively associated with monitors, drives, pumps, and other components through suitable interface hardware and/or software. Suitable software for the control of a three-dimensional printing or fabrication method and apparatus as described herein includes, but is not limited to, the ReplicatorG open source 3d printing program, 3DPrint™ controller software from 3D systems, Slic3r, Skeinforge, KIS Sheer, Repetier-Host, PrintRun, Cura, etc., including combinations thereof.

Process parameters to directly or indirectly monitor, continuously or intermittently, during the process (e.g., during one, some or all of said filling, irradiating and advancing steps) include, but are not limited to, irradiation intensity, temperature of carrier, polymerizable liquid in the build zone, temperature of growing product, temperature of build plate, pressure, speed of advance, pressure, force (e.g., exerted on the build plate through the carrier and product being fabricated), strain (e.g., exerted on the carrier by the growing product being fabricated), thickness of release layer, etc.

Known parameters that may be used in feedback and/or feed-forward control systems include, but are not limited to, expected consumption of polymerizable liquid (e.g., from the known geometry or volume of the article being fabricated), degradation temperature of the polymer being formed from the polymerizable liquid, etc.

Process conditions to directly or indirectly control, continuously or step- wise, in response to a monitored parameter, and/or known parameters (e.g., during any or all of the process steps noted above), include, but are not limited to, rate of supply of polymerizable liquid, temperature, pressure, rate or speed of advance of carrier, intensity of irradiation, duration of irradiation (e.g., for each "slice"), etc.

For example, the temperature of the polymerizable liquid in the build zone, or the temperature of the build plate, can be monitored, directly or indirectly, with an appropriate thermocouple, non-contact temperature sensor (e.g., an infrared temperature sensor), or other suitable temperature sensor, to determine whether the temperature exceeds the degradation temperature of the polymerized product. If so, a process parameter may be adjusted through a controller to reduce the temperature in the build zone and/or of the build plate. Suitable process parameters for such adjustment may include: decreasing temperature with a cooler, decreasing the rate of advance of the carrier, decreasing intensity of the irradiation, decreasing duration of radiation exposure, etc.

In addition, the intensity of the irradiation source (e.g., an ultraviolet light source such as a mercury lamp) may be monitored with a photodetector to detect a decrease of intensity from the irradiation source (e.g., through routine degradation thereof during use). If detected, a process parameter may be adjusted through a controller to accommodate the loss of intensity. Suitable process parameters for such adjustment may include: increasing temperature with a heater, decreasing the rate of advance of the carrier, increasing power to the light source, etc.

As another example, control of temperature and/or pressure to enhance fabrication time may be achieved with heaters and coolers (individually, or in combination with one another and separately responsive to a controller), and/or with a pressure supply (e.g., pump, pressure vessel, valves and combinations thereof) and/or a pressure release mechanism such as a controllable valve (individually, or in combination with one another and separately responsive to a controller).

In some embodiments the controller is configured to maintain the gradient of polymerization zone described herein (see, e.g., FIG. 1) throughout the fabrication of some or all of the final product. The specific configuration (e.g., times, rate or speed of advancing, radiation intensity, temperature, etc.) will depend upon factors such as the nature of the specific polymerizable liquid and the product being created. Configuration to maintain the gradient of polymerization zone may be carried out empirically, by entering a set of process parameters or instructions previously determined, or determined through a series of test runs or "trial and error"; configuration may be provided through pre-determined instructions; configuration may be achieved by suitable monitoring and feedback (as discussed above), combinations thereof, or in any other suitable manner.

In some embodiments, a method and apparatus as described above may be controlled by a software program running in a general purpose computer with suitable interface hardware between that computer and the apparatus described above. Numerous alternatives are commercially available. Non-limiting examples of one combination of components is shown in FIGS 3 to 5, where "Microcontroller" is Parallax Propeller, the Stepper Motor Driver is Sparkfun EasyDriver, the LED Driver is a Luxeon Single LED Driver, the USB to Serial is a Parallax USB to Serial converter, and the DLP System is a Texas Instruments LightCrafter system.

4. General Methods.

As noted above, the present invention provides a method of forming a three-dimensional object such as a microfluidic device, comprising the steps of: (a) providing a carrier and a build plate, said build plate comprising a semipermeable member, said semipermeable member comprising a build surface and a feed surface separate from said build surface, with said build surface and said carrier defining a build region therebetween, and with said feed surface in fluid contact with a polymerization inhibitor; then (concurrently and/or sequentially) (b) filling said build region with a polymerizable liquid, said polymerizable liquid contacting said build segment, (c) irradiating said build region through said build plate to produce a solid polymerized region in said build region, with a liquid film release layer comprised of said polymerizable liquid formed between said solid polymerized region and said build surface, the polymerization of which liquid film is inhibited by said polymerization inhibitor; and (d) advancing said carrier with said polymerized region adhered thereto away from said build surface on said stationary build plate to create a subsequent build region between said polymerized region and said top zone. In general the method includes (e) continuing and/or repeating steps (b) through (d) to produce a subsequent polymerized region adhered to a previous polymerized region until the continued or repeated deposition of polymerized regions adhered to one another forms said three-dimensional object.

Since no mechanical release of a release layer is required, or no mechanical movement of a build surface to replenish oxygen is required, the method can be carried out in a continuous fashion, though it will be appreciated that the individual steps noted above may be carried out sequentially, concurrently, or a combination thereof. Indeed, the rate of steps can be varied over time depending upon factors such as the density and/or complexity of the region under fabrication.

Also, since mechanical release from a window or from a release layer generally requires that the carrier be advanced a greater distance from the build plate than desired for the next irradiation step, which enables the window to be recoated, and then return of the carrier back closer to the build plate (e.g., a "two steps forward one step back" operation), the present invention in some embodiments permits elimination of this "back-up" step and allows the carrier to be advanced unidirectionally, or in a single direction, without intervening movement of the window for re-coating, or "snapping" of a pre-formed elastic release-layer. However, in other embodiments of the invention, reciprocation is utilized not for the purpose of obtaining release, but for the purpose of more rapidly filling or pumping polymerizable liquid into the build region.

While the dead zone and the gradient of polymerization zone do not have a strict boundary therebetween (in those locations where the two meet), the thickness of the gradient of polymerization zone is in some embodiments at least as great as the thickness of the dead zone. Thus, in some embodiments, the dead zone has a thickness of from 0.01, 0.1, 1, 2, or 10 microns up to 100, 200 or 400 microns, or more, and/or said gradient of polymerization zone and said dead zone together have a thickness of from 1 or 2 microns up to 400, 600, or 1000 microns, or more. Thus the gradient of polymerization zone may be thick or thin depending on the particular process conditions at that time. Where the gradient of polymerization zone is thin, it may also be described as an active surface on the bottom of the growing three-dimensional object, with which monomers can react and continue to form growing polymer chains therewith. In some embodiments, the gradient of polymerization zone, or active surface, is maintained (while polymerizing steps continue) for a time of at least 5, 10, 15, 20 or 30 seconds, up to 5, 10, 15 or 20 minutes or more, or until completion of the three-dimensional product.

The method may further comprise the step of disrupting said gradient of polymerization zone for a time sufficient to form a cleavage line in said three-dimensional object (e.g., at a predetermined desired location for intentional cleavage, or at a location in said object where prevention of cleavage or reduction of cleavage is non-critical), and then reinstating said gradient of polymerization zone (e.g. by pausing, and resuming, the advancing step, increasing, then decreasing, the intensity of irradiation, and combinations thereof).

CLIP may be carried out in different operating modes operating modes (that is, different manners of advancing the carrier and build surface away from one another), including continuous, intermittent, reciprocal, and combinations thereof.

Thus in some embodiments, the advancing step is carried out continuously, at a uniform or variable rate, with either constant or intermittent illumination or exposure of the build area to the light source.

In other embodiments, the advancing step is carried out sequentially in uniform increments (e.g., of from 0.1 or 1 microns, up to 10 or 100 microns, or more) for each step or increment. In some embodiments, the advancing step is carried out sequentially in variable increments (e.g., each increment ranging from 0.1 or 1 microns, up to 10 or 100 microns, or more) for each step or increment. The size of the increment, along with the rate of advancing, will depend in part upon factors such as temperature, pressure, structure of the article being produced (e.g., size, density, complexity, configuration, etc.) In other embodiments of the invention, the advancing step is carried out continuously, at a uniform or variable rate.

In some embodiments, the rate of advance (whether carried out sequentially or continuously) is from about 0.1 1, or 10 microns per second, up to about to 100, 1 ,000, or 10,000 microns per second, again depending again depending on factors such as temperature, pressure, structure of the article being produced, intensity of radiation, etc.

In still other embodiments, the carrier is vertically reciprocated with respect to the build surface to enhance or speed the refilling of the build region with the polymerizable liquid. In some embodiments, the vertically reciprocating step, which comprises an upstroke and a downstroke, is carried out with the distance of travel of the upstroke being greater than the distance of travel of the downstroke, to thereby concurrently carry out the advancing step (that is, driving the carrier away from the build plate in the Z dimension) in part or in whole.

In some embodiments, the solidifiable or polymerizable liquid is changed at least once during the method with a subsequent solidifiable or polymerizable liquid (e.g., by switching a "window" or "build surface" and associated reservoir of polymerizable liquid in the apparatus); optionally where the subsequent solidifiable or polymerizable liquid is cross-reactive with each previous solidifiable or polymerizable liquid during the subsequent curing, to form an object having a plurality of structural segments covalently coupled to one another, each structural segment having different structural (e.g., tensile) properties (e.g., a rigid housing or connector segment, covalently coupled to a flexible valve, tube, or macro-to-micro interface segment).

Once the three-dimensional intermediate is formed, it may be removed from the carrier, optionally washed, any supports optionally removed, any other modifications optionally made (cutting, welding, adhesively bonding, joining, grinding, drilling, etc.), and then heated and/or microwave irradiated sufficiently to further cure the resin and form the three dimensional object. Of course, additional modifications may also be made following the heating and/or microwave irradiating step.

Washing may be carried out with any suitable organic or aqueous wash liquid, or combination thereof, including solutions, suspensions, emulsions, microemulsions, etc. Examples of suitable wash liquids include, but are not limited to water, alcohols (e.g., methanol, ethanol, isopropanol, etc.), benzene, toluene, etc. Such wash solutions may optionally contain additional constituents such as surfactants, etc. A currently preferred wash liquid is a 50:50 (volume:volume) solution of water and isopropanol. Wash methods such as those described in US Patent No. 5,248,456 may be employed and are included herein. After the intermediate is formed, optionally washed, etc., as described above, it is then heated and/or microwave irradiated to further cure the same. Heating may be active heating (e.g., in an oven, such as an electric, gas, or solar oven), or passive heating (e.g., at ambient temperature). Active heating will generally be more rapid than passive heating and in some embodiments is preferred, but passive heating— such as simply maintaining the intermediate at ambient temperature for a sufficient time to effect further cure— is in some embodiments preferred.

In some embodiments, the heating step is carried out at at least a first temperature and a second temperature, with the first temperature greater than ambient temperature, the second temperature greater than the first temperature, and the second temperature less than 300 °C (e.g., with ramped or step-wise increases between ambient temperature and the first temperature, and/or between the first temperature and the second temperature).

For example, the intermediate may be heated in a stepwise manner at a first oven temperature of about 70°C to about 150°C, and then at a second temperature of about 150°C to 200 or 250 °C, with the duration of each heating depending on the size, shape, and/or thickness of the intermediate. In another embodiment, the intermediate may be cured by a ramped heating schedule, with the temperature ramped from ambient temperature through a temperature of 70 to 150 °C, and up to a final oven temperature of 250 or 300 °C, at a change in heating rate of 0.5°C per minute, to 5 °C per minute. (See, e.g., US Patent No. 4,785,075).

As described further below, in some embodiments the filling step is carried out by forcing said polymerizable liquid into said build region under pressure. In such a case, the advancing step or steps may be carried out at a rate or cumulative or average rate of at least 0.1, 1 , 10, 50, 100, 500 or 1000 microns per second, or more. In general, the pressure may be whatever is sufficient to increase the rate of said advancing step(s) at least 2, 4, 6, 8 or 10 times as compared to the maximum rate of repetition of said advancing steps in the absence of said pressure. Where the pressure is provided by enclosing an apparatus such as described above in a pressure vessel and carrying the process out in a pressurized atmosphere (e.g., of air, air enriched with oxygen, a blend of gasses, pure oxygen, etc.) a pressure of 10, 20, 30 or 40 pounds per square inch (PSI) up to, 200, 300, 400 or 500 PSI or more, may be used. For fabrication of large irregular objects higher pressures may be less preferred as compared to slower fabrication times due to the cost of a large high pressure vessel. In such an embodiment, both the feed surface and the polymerizable liquid can be in fluid contact with the same compressed gas (e.g., one comprising from 20 to 95 percent by volume of oxygen, the oxygen serving as the polymerization inhibitor). On the other hand, when smaller items are fabricated, or a rod or fiber is fabricated that can be removed or exited from the pressure vessel as it is produced through a port or orifice therein, then the size of the pressure vessel can be kept smaller relative to the size of the product being fabricated, and higher pressures can (if desired) be more readily utilized.

As noted above, the irradiating step is in some embodiments is carried out with patterned irradiation. The patterned irradiation may be a fixed pattern or may be a variable pattern created by a pattern generator (e.g., a DLP) as discussed above, depending upon the particular item being fabricated.

When the patterned irradiation is a variable pattern rather than a pattern that is held constant over time, then each irradiating step may be any suitable time or duration depending on factors such as the intensity of the irradiation, the presence or absence of dyes in the polymerizable material, the rate of growth, etc. Thus in some embodiments each irradiating step can be from 0.001, 0.01, 0.1, 1 or 10 microseconds, up to 1, 10, or 100 minutes, or more, in duration. The interval between each irradiating step is in some embodiments preferably as brief as possible, e.g., from 0.001, 0.01, 0.1, or 1 microseconds up to 0.1, 1, or 10 seconds.

In some embodiments the build surface is flat; in others the build surface is irregular such as convexly or concavely curved, or has walls or trenches formed therein. In either case the build surface may be smooth or textured.

Curved and/or irregular build plates or build surfaces can be used in fiber or rod formation, to provide different materials to a single object being fabricated (that is, different polymerizable liquids to the same build surface through channels or trenches formed in the build surface, each associated with a separate liquid supply, etc.).

Carrier Feed Channels for Polymerizable liquid. While polymerizable liquid may be provided directly to the build plate from a liquid conduit and reservoir system, in some embodiments the carrier includes one or more feed channels therein. The carrier feed channel(s) are in fluid communication with the polymerizable liquid supply, for example a reservoir and associated pump. Different carrier feed channels may be in fluid communication with the same supply and operate simultaneously with one another, or different carrier feed channels may be separately controllable from one another (for example, through the provision of a pump and/or valve for each). Separately controllable feed channels may be in fluid communication with a reservoir containing the same polymerizable liquid, or may be in fluid communication with a reservoir containing different polymerizable liquids. Through the use of valve assemblies, different polymerizable liquids may in some embodiments be alternately fed through the same feed channel, if desired. 5. Reciprocating feed of polymerizable liquid.

In an embodiment of the present invention, the carrier is vertically reciprocated with respect to the build surface to enhance or speed the refilling of the build region with the polymerizable liquid.

In some embodiments, the vertically reciprocating step, which comprises an upstroke and a downstroke, is carried out with the distance of travel of the upstroke being greater than the distance of travel of the downstroke, to thereby concurrently carry out the advancing step (that is, driving the carrier away from the build plate in the Z dimension) in part or in whole.

In some embodiments, the speed of the upstroke gradually accelerates (that is, there is provided a gradual start and/or gradual acceleration of the upstroke, over a period of at least 20, 30, 40, or 50 percent of the total time of the upstroke, until the conclusion of the upstroke, or the change of direction which represents the beginning of the downstroke. Stated differently, the upstroke begins, or starts, gently or gradually.

In some embodiments, the speed of the downstroke gradually decelerates. That is, there is provided a gradual termination and/or gradual deceleration of the downstroke, over a period of at least 20, 30, 40, or 50 percent of the total time of the downstroke. Stated differently, the downstroke concludes, or ends, gently or gradually.

While in some embodiments there is an abrupt end, or abrupt deceleration, of the upstroke, and an abrupt beginning or deceleration of the downstroke (e.g., a rapid change in vector or direction of travel from upstroke to downstroke), it will be appreciated that gradual transitions may be introduced here, as well (e.g., through introduction of a "plateau" or pause in travel between the upstroke and downstroke). It will also be appreciated that, while the reciprocating step may be a single upstroke and downstroke, the reciprocations may occur in linked groups thereof, of the same or different amplitude and frequency.

In some embodiments, the vertically reciprocating step is carried out over a total time of from 0.01 or 0.1 seconds up to 1 or 10 seconds (e.g., per cycle of an upstroke and a downstroke).

In some embodiments, the upstroke distance of travel is from 0.02 or 0.2 millimeters (or 20 or 200 microns) to 1 or 10 millimeters (or 1000 to 10,000 microns). The distance of travel of the downstroke may be the same as, or less than, the distance of travel of the upstroke, where a lesser distance of travel for the downstroke serves to achieve the advancing of the carrier away from the build surface as the three-dimensional object is gradually formed.

Preferably the vertically reciprocating step, and particularly the upstroke thereof, does not cause the formation of gas bubbles or a gas pocket in the build region, but instead the build region remains filled with the polymerizable liquid throughout the reciprocation steps, and the gradient of polymerization zone or region remains in contact with the "dead zone" and with the growing object being fabricated throughout the reciprocation steps. As will be appreciated, a purpose of the reciprocation is to speed or enhance the refilling of the build region, particularly where larger build regions are to be refilled with polymerizable liquid, as compared to the speed at which the build region could be refilled without the reciprocation step.

In some embodiments, the advancing step is carried out intermittently at a rate of 1, 2, 5 or 10 individual advances per minute up to 300, 600, or 1000 individual advances per minute, each followed by a pause during which an irradiating step is carried out. It will be appreciated that one or more reciprocation steps (e.g., upstroke plus downstroke) may be carried out within each advancing step. Stated differently, the reciprocating steps may be nested within the advancing steps.

In some embodiments, the individual advances are carried out over an average distance of travel for each advance of from 10 or 50 microns to 100 or 200 microns (optionally including the total distance of travel for each vertically reciprocating step, e.g., the sum of the upstroke distance minus the downstroke distance).

Apparatus for carrying out the invention in which the reciprocation steps described herein are implemented substantially as described above, with the drive associated with the carrier, and/or with an additional drive operatively associated with the transparent member, and with the controller operatively associated with either or both thereof and configured to reciprocate the carrier and transparent member with respect to one another as described above.

6. Increased speed of fabrication by increasing light intensity.

In general, it has been observed that speed of fabrication can increase with increased light intensity. In some embodiments, the light is concentrated or "focused" at the build region to increase the speed of fabrication. This may be accomplished using an optical device such as an objective lens.

The speed of fabrication may be generally proportional to the light intensity. For example, the build speed in millimeters per hour may be calculated by multiplying the light intensity in milliWatts per square centimeter and a multiplier. The multiplier may depend on a variety of factors, including those discussed below. A range of multiplers, from low to high, may be employed. On the low end of the range, the multiplier may be about 10, 15, 20 or 30. On the high end of the multiplier range, the multiplier may be about 150, 300, 400 or more.

The relationships described above are, in general, contemplated for light intensities of from 1, 5 or 10 milliWatts per square centimeter, up to 20 or 50 milliWatts per square centimeter. Certain optical characteristics of the light may be selected to facilitate increased speed of fabrication. By way of example, a band pass filter may be used with a mercury bulb light source to provide 365 ± 10 nm light measured at Full Width Half Maximum (FWHM). By way of further example, a band pass filter may be used with an LED light source to provide 375 ± 15 nm light measured at FWHM.

As noted above, poymerizable liquids used in such processes are, in general, free radical polymerizable liquids with oxygen as the inhibitor, or acid-catalyzed or cationically polymerizable liquids with a base as the inhibitor. Some specific polymerizable liquids will of course cure more rapidly or efficiently than others and hence be more amenable to higher speeds, though this may be offset at least in part by further increasing light intensity.

At higher light intensities and speeds, the "dead zone" may become thinner as inhibitor is consumed. If the dead zone is lost then the process will be disrupted. In such case, the supply of inhibitor may be enhanced by any suitable means, including providing an enriched and/or pressurized atmosphere of inhibitor, a more porous semipermeable member, a stronger or more powerful inhibitor (particularly where a base is employed), etc.

In general, lower viscosity polymerizable liquids are more amenable to higher speeds, particularly for fabrication of articles with a large and/or dense cross section (although this can be offset at least in part by increasing light intensity). Polymerizable liquids with viscosities in the range of 50 or 100 centipoise, up to 600, 800 or 1000 centipoise or more (as measured at room temperature and atmospheric pressure with a suitable device such as a HYDRAMOTION REACTAVISC™ Viscometer, available from Hydramotion Ltd, 1 York Road Business Park, Malton, York Y017 6YA England). In some embodiments, where necessary, the viscosity of the polymerizable liquid can advantageously be reduced by heating the polymerizable liquid, as described above.

In some embodiments, such as fabrication of articles with a large and/or dense cross- section, speed of fabrication can be enhanced by introducing reciprocation to "pump" the polymerizable liquid, as described above, and/or the use of feeding the polymerizable liquid through the carrier, as also described above, and/or heating and/or pressurizing the polymerizable liquid, as also described above.

7. Tiling.

It may be desirable to use more than one light engine to preserve resolution and light intensity for larger build sizes. Each light engine may be configured to project an image (e.g., an array of pixels) into the build region such that a plurality of "tiled" images are projected into the build region. As used herein, the term "light engine" can mean an assembly including a light source, a DLP device such as a digital micromirror device and an optical device such as an objective lens. The "light engine" may also include electronics such as a controller that is operatively associated with one or more of the other components.

In some embodiments, a configuration with the overlapped images is employed with some form of "blending" or "smoothing" of the overlapped regions as generally discussed in, for example, U.S. Patent Nos. 7,292,207, 8,102,332, 8,427,391, 8,446,431 and U.S. Patent Application Publication Nos. 2013/0269882, 2013/0278840 and 2013/0321475, the disclosures of which are incorporated herein in their entireties.

The tiled images can allow for larger build areas without sacrificing light intensity, and therefore can facilitate faster build speeds for larger objects. It will be understood that more than two light engine assemblies (and corresponding tiled images) may be employed. Various embodiments of the invention employ at least 4, 8, 16, 32, 64, 128 or more tiled images.

8. Dual hardening polymerizable liquids.

As noted above, in some embodiments of the invention, the polymerizable liquid comprises a first light polymerizable component (sometimes referred to as "Part A" herein) and a second component that solidifies by another mechanism, or in a different manner from, the first component (sometimes referred to as "Part B" herein). Numerous embodiments thereof may be carried out. In the following, note that, where particular acrylates such as methacrylates are described, other acrylates may also be used.

Part A chemistry. In some embodiments of the present invention, a resin will have a first component, termed "Part A." Part A comprises or consists of a mix of monomers and/or prepolymers that can be polymerized by exposure to actinic radiation or light. This resin can have a functionality of 2 or higher (though a resin with a functionality of 1 can also be used when the polymer does not dissolve in its monomer). A purpose of Part A is to "lock" the shape of the object being printed or create a scaffold for the one or more additional components (e.g., Part B). Importantly, Part A is present at or above the minimum quantity needed to maintain the shape of the object being formed after the initial solidification. In some embodiments, this amount corresponds to less than ten, twenty, or thirty percent by weight of the total resin (polymerizable liquid) composition.

In some embodiments, Part A can react to form a cross-linked polymer network or a solid homopolymer.

Examples of suitable reactive end groups suitable for Part A constituents, monomers, or prepolymers include, but are not limited to: acrylates, methacrylates, -olefins, N-vinyls, acrylamides, methacrylamides, styrenics, epoxides, thiols, 1,3-dienes, vinyl halides, acrylonitriles, vinyl esters, maleimides, and vinyl ethers.

An aspect of the solidification of Part A is that it provides a scaffold in which a second reactive resin component, termed "Part B," can solidify during a second step (which may occur concurrently with or following the solidification of Part A). This secondary reaction preferably occurs without significantly distorting the original shape defined during the solidification of Part A. Alternative approaches would lead to a distortion in the original shape in a desired manner.

In particular embodiments, when used in the methods and apparatus described herein, the solidification of Part A is continuously inhibited during printing within a certain region, by oxygen or amines or other reactive species, to form a liquid interface between the solidified part and an inhibitor-permeable film or window (e.g., is carried out by continuous liquid interphase/interface printing).

Part B chemistry. Part B may comprise, consist of or consist essentially of a mix of monomers and/or prepolymers that possess reactive end groups that participate in a second solidification reaction after the Part A solidification reaction. In some embodiments, Part B could be added simultaneously to Part A so it is present during the exposure to actinide radiation, or Part B could be infused into the object made during the 3D printing process in a subsequent step. Examples of methods used to solidify Part B include, but are not limited to, contacting the object or scaffold to heat, water or water vapor, light at a different wavelength than that at which Part A is cured, catalysts, (with or without additional heat), evaporation of a solvent from the polymerizable liquid {e.g., using heat, vacuum, or a combination thereof), microwave irradiation, etc., including combinations thereof.

Examples of suitable reactive end group pairs suitable for Part B constituents, monomers or prepolymers include, but are not limited to: epoxy/amine, epoxy/hydroxyl, isocyanateVhydroxyl, IsocyanateVamine, isocyanate/carboxylic acid, anhydride/amine, amine/carboxylic acid, amine/ester, hydroxyl/carboxylic acid, hydroxyl/acid chloride, amine/acid chloride, vinyl/Si-H (hydrosilylation), Si-Cl /hydroxyl, Si-Cl/amine, hydroxyl/aldehyde, amine/aldehyde, alkyne/Azide (also known as one embodiment of "Click Chemistry," along with additional reactions including thiolene, Michael additions, Diels-Alder reactions, nucleophilic substitution reactions, etc.), alkene/Sulfur (polybutadiene vulcanization), alkene/thiol, alkyne/thiol, hydroxyl/halide, isocyanateVwater (polyurethane foams), Si-OH/hydroxyl, Si- OH/water, Si-OH/Si-H (tin catalyzed silicone), Si-OH/Si-OH (tin catalyzed silicone), Perfluorovinyl (coupling to form perfluorocyclobutane), etc., where *Isocyanates include protected isocyanates (e.g. oximes), diene/dienophiles for Diels-Alder reactions, olefin metathesis polymerization, olefin polymerization using Ziegler-Natta catalysis, ring-opening polymerization (including ring-opening olefin metathesis polymerization, lactams, lactones, Siloxanes, epoxides, cyclic ethers, imines, cyclic acetals, etc.), etc.

Cyanoacryate (moisture initiated). Other reactive chemistries suitable for Part B will be recognizable by those skilled in the art. Part B components useful for the formation of polymers described in "Concise Polymeric Materials Encyclopedia" and the "Encyclopedia of Polymer Science and Technology" are hereby incorporated by reference.

Elastomers. A particularly useful embodiment for implementing the invention is for the formation of elastomers. Tough, high-elongation elastomers are difficult to achieve using only liquid UV-curable precursors. However, there exist many thermally cured materials (polyurethanes, silicones, natural rubber) that result in tough, high-elongation elastomers after curing. These thermally curable elastomers on their own are generally incompatible with most 3D printing techniques.

In embodiments of the current invention, small amounts {e.g., less than 20 percent by weight) of a low- viscosity UV curable material (Part A) are blended with thermally-curable precursors to form (preferably tough) elastomers (e.g. polyurethanes, polyureas, or copolymers thereof (e.g., poly(urethane-urea), and silicones) (Part B). The UV curable component is used to solidify an object into the desired shape using 3D printing as described herein and a scaffold for the elastomer precursors in the polymerizable liquid. The object can then be heated after printing, thereby activating the second component, resulting in an object comprising the elastomer.

Adhesion of printed objects. In some embodiments, it may be useful to define the shapes of multiple objects using the solidification of Part A, align those objects in a particular configuration, such that there is a hermetic seal between the objects, then activate the secondary solidification of Part B. In this manner, strong adhesion between parts can be achieved during production.

Fusion of particles as Part B. In some embodiments, "Part B" may simply consist of small particles of a pre-formed polymer. After the solidification of Part A, the object may be heated above the glass transition temperature of Part B in order to fuse the entrapped polymeric particles.

Evaporation of solvent as Part B. In some embodiments, "Part B" may consist of a preformed polymer dissolved in a solvent. After the solidification of Part A into the desired object, the object is subjected to a process (e.g., heat + vacuum) that allows for evaporation of the solvent for Part B, thereby solidifying Part B. Thermally cleavable end groups. In some embodiments, the reactive chemistries in Part A can be thermally cleaved to generate a new reactive species after the solidification of Part A. The newly formed reactive species can further react with Part B in a secondary solidification. An exemplary system is described by Velankar, Pezos and Cooper, Journal of Applied Polymer Science, 62, 1361-1376 (1996). Here, after UV-curing, the acrylate/ methacrylate groups in the formed object are thermally cleaved to generate diisocyanate prepolymers that further react with blended chain-extender to give high molecular weight polyurethanes/polyureas within the original cured material or scaffold. Such systems are, in general, dual-hardening systems that employ blocked or reactive blocked prepolymers, as discussed in greater detail below.

Methods of mixing components. In some embodiments, the components may be mixed in a continuous manner prior to being introduced to the printer build plate. This may be done using multi-barrel syringes and mixing nozzles. For example, Part A may comprise or consist of a UV-curable di(meth)acrylate resin, Part B may comprise or consist of a diisocyanate prepolymer and a polyol mixture. The polyol can be blended together in one barrel with Part A and remain unreacted. A second syringe barrel would contain the diisocyanate of Part B. In this manner, the material can be stored without worry of "Part B" solidifying prematurely. Additionally, when the resin is introduced to the printer in this fashion, a constant time is defined between mixing of all components and solidification of Part A.

Additional examples of "dual cure" polymerizable liquids (or "resins"), and methods that may be used in carrying out the present invention include, but are not limited to, those set forth in J. RoUand et al, Method of Producing Polyurethane Three-Dimensional Objects from Materials having Multiple Mechanisms of Hardening, PCT Publication No. WO 2015/200179 (published 30 Dec. 2015); J. RoUand et al., Methods of Producing Three-Dimensional Objects from Materials Having Multiple Mechanisms of Hardening, PCT Publication No. WO 2015/200173 (published 30 Dec. 2015); J. RoUand et al., Three-Dimensional Objects Produced from Materials Having Multiple Mechanisms of Hardening, PCT Publication No. WO/2015/200189 (published 30 Dec. 2015); J. RoUand et al., Polyurethane Resins Having Multiple Mechanisms of Hardening for Use in Producing Three-Dimensional Objects published 30 Dec. 2015); and

J. RoUand et al., Method of Producing Three-Dimensional Objects from Materials having

Multiple Mechanisms of Hardening, US Patent Application No. 14/977,822 (filed 22 Dec. 2015); J. Rolland et al., Method of Producing Polyurethane Three-Dimensional Objects from Materials having Multiple Mechanisms of Hardening, US Patent Application No. 14/977,876 (filed 22 Dec. 2015), J. Rolland et al., Three-Dimensional Objects Produced from Materials having Multiple Mechanisms of Hardening, US Patent Application No. 14/977,938 (filed 22 Dec. 2015), and J. Rolland et al., Polyurethane Resins having Multiple Mechanisms of Hardening for Use in Producing Three-Dimensional Objects, US Patent Application No. 14/977,974 (filed 22 Dec. 2015);

the disclosures of all of which are incorporated by reference herein in their entirety.

Other additive manufacturing techniques. It will be clear to those skilled in the art that the materials described in the current invention will be useful in other additive manufacturing techniques including fused deposition modeling (FDM), solid laser sintering (SLS), and Ink-jet methods. For example, a melt-processed acrylonitrile-butadiene-styrene resin may be formulated with a second UV-curable component that can be activated after the object is formed by FDM. New mechanical properties could be achieved in this manner. In another alternative, melt- processed unvulcanized rubber is mixed with a vulcanizing agent such as sulfur or peroxide, and the shape set through FDM, then followed by a continuation of vulcanization.

9. Dual hardening polymerizable liquids employing blocked constituents and thermally cleavable blocking groups.

In some embodiments, where the solidifying and/or curing step (d) is carried out subsequent to the irradiating step {e.g., by heating); the solidifying and/or curing step (d) is carried out under conditions in which the solid polymer scaffold degrades and forms a constituent necessary for the polymerization of the second component (e.g., a constituent such as (i) a prepolymer, (ii) a diisocyanate or polyisocyanate, and/or (Hi) a polyol and/or diol, where said second component comprises a polyurethane/polyurea resin). Such methods may involve the use of reactive or non-reactive blocking groups on or coupled to a constituent of the first component, such that the constituent participates in the first hardening or solidifying event, and when de-protected (yielding free constituent and free blocking groups or blocking agents) generates a free constituent that can participate in the second solidifying and/or curing event. Non-limiting examples of such methods are described further below.

A. Dual hardening polymerizable liquids employing blocked prepolymers and thermally cleavable blocking groups. Some "dual cure" embodiments of the present invention are, in general, a method of forming a three-dimensional object, comprising:

(b) filling the build region with a polymerizable liquid, the polymerizable liquid comprising a mixture of a blocked or reactive blocked prepolymer, optionally but in some embodiments preferably a reactive diluent, a chain extender, and a photoinitiator; (c) irradiating the build region with light through the optically transparent member to form a (rigid, compressible, collapsible, flexible or elastic) solid blocked polymer scaffold from the blocked prepolymer and optionally the reactive diluent while concurrently advancing the carrier away from the build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, the three-dimensional object, with the intermediate containing the chain extender; and then

(d) heating the three-dimensional intermediate sufficiently to de-block the blocked polymer and form an unblocked prepolymer that in turn polymerizes with the chain extender to form the three-dimensional product from the three-dimensional intermediate.

In some embodiments, the blocked or reactive blocked prepolymer comprises a polyisocyanate.

In some embodiments, the blocked or reactive blocked prepolymer is a compound of the formula A-X-A, where X is a hydrocarbyl group and each A is an independently selected substituent of Formula X:

(X) where R is a hydrocarbyl group and Z is a blocking group, said blocking group optionally having a reactive terminal group (e.g., a polymerizable end group such as an epoxy, alkene, alkyne, or thiol end group, for example an ethylenically unsaturated end group such as a vinyl ether). In a particular example, each A is an independently selected substituent of Formula XI:

where R is as given above.

In some embodiments, the blocked or reactive blocked prepolymer comprises a polyisocyanate oligomer produced by the reaction of at least one diisocyanate (e.g., a diisocyanate such as hexamethylene diisocyanate (HDI), bis-(4-isocyanatocyclohexyl)methane (HMD I), isophorone diisocyanate (IPDI), etc., a triisocyanate, etc.) with at least one polyol (e.g., a polyether or polyester or polybutadiene diol).

In some embodiments, the reactive blocked prepolymer is blocked by reaction of a polyisocyanate with an amine methacrylate monomer blocking agent (e.g., tertiary- butylaminoethyl methacrylate (TBAEMA) Tertiary pentylaminoethyl methacrylate (TPAEMA), Tertiary hexylaminoethyl methacrylate (THAEMA), Tertiary-butylaminopropyl methacrylate (TBAPMA), and mixtures thereof (see, e.g., US Patent Application Publication No. 20130202392). Note that all of these can be used as diluents as well.

In some embodiments, the reactive diluent comprises styrene or derivatives thereof, acrylic acid or derivatives thereof, vinyl ethers, vinyl esters, polymeric materials containing any one or more of these, and combinations of two or more of the foregoing (e.g., acrylonitrile, styrene, divinyl benzene, vinyl toluene, methyl acrylate, ethyl acrylate, butyl acrylate, methyl methacrylate, amine methacrylates as described above, and mixtures of any two or more of these) (see, e.g. , US Patent Application Publication No. 20140072806).

In some embodiments, the chain extender comprises at least one diol, diamine or dithiol chain extender (e.g., ethylene glycol, 1,3 -propanediol, 1,2-propanediol, 1,4-butanediol, 1,5- pentanediol, 1,6-hexanediol, 1 ,7-heptanediol, 1 ,8-octanediol, 1 ,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1 ,2-cyclohexanedimethanol, 1 ,4-cyclohexanedimethanol, the corresponding diamine and dithiol analogs thereof, lysine ethyl ester, arginine ethyl ester, p- alanine-based diamine, and random or block copolymers made from at least one diisocyanate and at least one diol, diamine or dithiol chain extender; see, e.g., US Patent Application Publication No. 20140010858). Note also that, when dicarboxylic acid is used as the chain extender, polyesters (or carbamate-carboxylic acid anhydrides) are made.

In some embodiments, the polymerizable liquid comprises:

from 5 or 20 or 40 percent by weight to 60 or 80 or 90 percent by weight of the blocked or reactive blocked prepolymer;

from 10 or 20 percent by weight to 30 or 40 or 50 percent by weight of the reactive diluent;

from 5 or 10 percent by weight to 20 or 30 percent by weight of the chain extender; and from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of the photoinitiator. Optional additional ingredients, such as dyes, fillers, surfactants, etc., may also be included, as discussed in greater detail above. An advantage of some embodiments of the invention is that, because these polymerizable liquids do not rapidly polymerize upon mixing, they may be formulated in advance, and the filling step carried out by feeding or supplying the polymerizable liquid to the build region from a single source (e.g., a single reservoir containing the polymerizable liquid in pre-mixed form), thus obviating the need to modify the apparatus to provide separate reservoirs and mixing capability.

Three-dimensional objects such as micro fluidic devices made by the process are, in some embodiments, collapsible or compressible (that is, elastic (e.g., has a Young's modulus at room temperature of from about 0.001, 0.01 or 0.1 gigapascals to about 1, 2 or 4 gigapascals, and/or a tensile strength at maximum load at room temperature of about 0.01, 0.1, or 1 to about 50, 100, or 500 megapascals, and/or a percent elongation at break at room temperature of about 10, 20 50 or 100 percent to 1000, 2000, or 5000 percent, or more).

An additional example of the preparation of a blocked reactive prepolymer is shown in the Scheme below:

a Rate and product split depend on catalyst: Zn Octoate --> slow, mainly II Urea; Sn⁺ --> faster, mix.

One can use similar chemistry to that described above to form a reactive blocked diioscyanate, a reactive blocked chain extender, or a reactive blocked prepolymer.

A non-limiting example of a dual cure system employing a thermally cleavable end group is shown in the FIG. 10A and the Scheme below: Pol ol

Without wishing to be bound to any underlying mechanism, in some embodiments, during thermal cure, blocking agent is cleaved and diisocyanate prepolymer is re-formed and quickly reacts with chain extenders or additional soft segment to form thermoplastic or thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), as follows:

X/X N/X/N/X X/N/N/N/N/X/V* ΛΛ/WW^{1 1}

Segmented Thermoplastic Polyurethane

Alternative mechanisms such as those described in section B below may also be implemented or involved.

In the scheme above, the dual cure resin is comprised of a UV-curable (meth)acrylate blocked polyurethane (ABPU), a reactive diluent, a photoinitiator, and a chain extender(s). The reactive diluent (10-50 wt%) is an acrylate or methacrylate that helps to reduce the viscosity of ABPU and will be copolymerized with the ABPU under UV irradiation. The photoinitiator (generally about 1 wt%) can be one of those commonly used UV initiators, examples of which include but are not limited to such as acetophenones (diethoxyacetophenone for example), phosphine oxides [diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, phenylbis(2,4,6- trimethylbenzoyl)phosphine oxide (PPO), Irgacure 369, etc.

After UV curing to form a intermediate shaped product having blocked polyurethane oligomers as a scaffold, and carrying the chain extender, the ABPU resin is subjected to a thermal cure, during which a high molecular weight polyurethane/polyurea is formed by a spontaneous reaction between the polyurethane/polyurea oligomers and the chain extender(s). The polyurethane/polyurea oligomer is generated by deblocking of the isocyanate end groups in ABPU. The thermal cure time needed can vary depending on the temperature, size, shape, and density of the product, but is typically between 1 to 6 hours depending on the specific ABPU systems, chain extenders and temperature.

One advantageous aspect of the foregoing is using a tertiary amine-containing methacrylate (e.g., t-butylaminoethyl methacrylate, TBAEMA) to terminate synthesized polyurethane/polyurea oligomers with isocyanate at both ends. Using acrylate or methacrylate containing hydroxyl groups to terminate polyurethane/polyurea oligomers with isocyanate ends is used in UV curing resins in the coating field. The formed urethane bonds between the isocyanate and hydroxyl groups are generally stable even at high temperatures. In embodiments of the present invention, the urea bond formed between the tertiary amine of TBAEMA and isocyanate of the oligomer becomes labile when heated to suitable temperature (for example, about 100 °C), regenerating the isocyanate groups that will react with the chain extender(s) during thermal-cure to form high molecular weight polyurethane (PU). While it is possible to synthesize other (meth)acrylate containing isocyanate blocking functionality as generally used (such as ε-caprolactam, 1 ,2,3-triazole, methyl ethyl ketoxime, diethyl malonate, etc.), the illustrative embodiment uses TBAEMA that is commercially available. The used chain extenders can be diols, diamines, triols, triamines or their combinations or others. Ethylene glycol, 1,4- butanediol, methylene dicyclohexylamine (H12MDA; or PACM as the commercial name from Air Products), hydroquinone bis(2-Hydroxyethyl) Ether (HQEE), 4,4'-Methylenebis(3-Chloro- 2,6-Diethylaniline) (MCDEA), 4,4'-methylene-bis-(2,6 diethylaniline) (MDEA), 4,4'- Methylenebis(2-chloroaniline) (MOCA) are the preferred chain extenders.

To produce an ABPU, TBAEMA may be used to terminate the isocyanate end groups of the oligomeric diisocyanate, which is derived from diisocyanate tipped polyols. The polyols (with hydroxyl functionality of 2) used can be polyethers [especially polytetramethylene oxide (PTMO), polypropylene glycol (PPG)], polyesters or polybutadiene. The molecular weight of these polyols can be 500 to 3000 Da, and 1000-2000 Da are currently preferred. In the presence of a catalyst (e.g., stannous octoate with 0.1-0.3 wt% to the weight of polyol; other tin catalysts or amine catalysts), diisocyanate (e.g., toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), hydrogenated MDI (HMDI), etc.) is added to the polyol with certain molar ratio (2: 1 molar ratio preferred) to block the end groups of the polyol (50 - 100 °C), resulting in an oligomer diisocyanate. TBAEMA is then added to the reaction (Note: moles(TBAEMA)*2+moles(polyol)*2 = moles(isocyanate)*2) to generate ABPU (under 50 - 60 °C). Inhibitors such as hydroquinone (100 - 500 ppm) can be used to inhibit polymerization of methacrylate during the reaction.

In general, a three-dimensional product of the foregoing methods comprises (i) a linear thermoplastic polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), (ii) a cross-linked thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), or (Hi) combinations thereof (optionally blended with de-blocked blocking group which is copolymerized with the reactive diluents(s), for example as an interpenetrating polymer network, a semi-interpenetrating polymer network, or as a sequential interpenetrating polymer network). ). In some example embodiments, the three-dimensional product may also include unreacted photoinitiator remaining in the three-dimensional formed object. For example, in some embodiments, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of the photoinitiator may remain in the three-dimensional formed object or the photoinitiator may be present in lower amounts or only a trace amount. In some example embodiments, the three- dimensional product may also include reacted photoinitiator fragments. For example, in some embodiments, the reacted photoinitiator fragments may be remnants of the first cure forming the intermediate product. For example, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of reacted photoinitiator fragments may remain in the three-dimensional formed object or the reacted photoinitiator fragments may be present in lower amounts or only a trace amount. In example embodiments, a three-dimensional product may comprise, consist of or consist essentially of all or any combination of a linear thermoplastic polyurethane, a cross-linked thermoset polyurethane, unreacted photoinitiator and reacted photoinitiator materials.

While this embodiment has been described above primarily with respect to reactive blocking groups, it will be appreciated that unreactive blocking groups may be employed as well.

In addition, while less preferred, it will be appreciated that processes as described above may also be carried out without a blocking agent, while still providing dual cure methods and products of the present invention.

In addition, while this embodiment has been described primarily with diol and diamine chain extenders, it will be appreciated that chain extenders with more than two reactive groups (polyol and polyamine chain extenders such as triols and triamine chain extenders) may be used to three dimensional objects comprised of a crosslinked thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea). These materials may be used in bottom-up additive manufacturing techniques such as the continuous liquid interface printing techniques described herein, or other additive manufacturing techniques as noted above and below.

B. Dual hardening polymerizable liquids employing blocked diisocyanates and thermally cleavable blocking groups. Another embodiment provides a method of forming a three-dimensional object comprised of polyurethane, polyurea, or copolymer thereof {e.g., poly(urethane-urea), said method comprising:

(a) providing a carrier and an optically transparent member having a build surface, said carrier and said build surface defining a build region therebetween;

(b) filling said build region with a polymerizable liquid, said polymerizable liquid comprising a mixture of (i) a blocked or reactive blocked diisocyanate, (ii) a polyol and/or polyamine, (Hi) a chain extender, (iv) a photoinitiator, and (v) optionally but in some embodiments preferably a reactive diluent (vi) optionally but in some embodiments preferably a pigment or dye, (vii) optionally but in some embodiments preferably a filler (e.g. silica),

(c) irradiating said build region with light through said optically transparent member to form a solid blocked diisocyanate scaffold from said blocked diisocyanate, and optionally said reactive diluent and advancing said carrier away from said build surface to form a three- dimensional intermediate having the same shape as, or a shape to be imparted to, said three- dimensional object, with said intermediate containing said chain extender and polyol and/or polyamine; and then

(d) heating said three-dimensional intermediate sufficiently to de-block said blocked diisocyanate and form an unblocked diisocyanate that in turn polymerizes with said chain extender and polyol and/or polyamine to form said three-dimensional product comprised of polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea), from said three- dimensional intermediate.

In some embodiments, the blocked or reactive blocked diisocyanate is a compound of the formula A'-X'-A', where X' is a hydrocarbyl group and each A' is an independently selected substituent of Formula X':

where R is a hydrocarbyl group and Z is a blocking group, said blocking group optionally having a reactive terminal group (e.g., a polymerizable end group such as an epoxy, alkene, alkyne, or thiol end group, for example an ethylenically unsaturated end group such as a vinyl ether). In a particular example, each A' is an independently selected substituent of Formula XI':

where is as given above.

Other constituents and steps of these methods are carried out in like manner as described in section 9A above.

In a non-limiting example, a blocked diisocyanate is prepared as shown in the Scheme below. Such blocked diisocyanates may be used in methods as shown in FIG. 10B.

OCN^NCO Diisocyanate

Methacrylate Blocked Diisocyanate (ABDI)

Without wishing to be bound by any particular underlying mechanism, in some embodiments, during thermal cure, the blocking agent is cleaved and the chain extender reacts to form thermoplastic or thermoset polyurethane, polyurea, or a copolymer thereof (e.g., poly(urethane- urea)), for example as shown below: H₂N NH₂ HO OH

R.

OCN NCO -

Soft Segment: Polyamine Polyol

Segmented Thermoplastic Polyurethane

In an alternative mechanism, the chain extender reacts with the blocked diisocyante, eliminates the blocking agent, in the process forming thermoplastic or thermoset polyurethane, polyurea, or a copolymer thereof (e.g., poly(urethane-urea)).

In general, a three-dimensional product of the foregoing methods comprises (i) a linear thermoplastic polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), a(ii) cross-linked thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), or (Hi) combinations thereof (optionally blended with de-blocked blocking group which is copolymerized with the reactive diluents(s), for example as an interpenetrating polymer network, a semi-interpenetrating polymer network, or as a sequential interpenetrating polymer network). In some example embodiments, the three-dimensional product may also include unreacted photoinitiator remaining in the three-dimensional formed object. For example, in some embodiments, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of the photoinitiator may remain in the three-dimensional formed object or the photoinitiator may be present in lower amounts or only a trace amount. In some example embodiments, the three- dimensional product may also include reacted photoinitiator fragments. For example, in some embodiments, the reacted photoinitiator fragments may be remnants of the first cure forming the intermediate product. For example, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of reacted photoinitiator fragments may remain in the three-dimensional formed object or the reacted photoinitiator fragments may be present in lower amounts or only a trace amount. In example embodiments, a three-dimensional product may comprise, consist of or consist essentially of all or any combination of a linear thermoplastic polyurethane, a cross-linked thermoset polyurethane, unreacted photoinitiator and reacted photoinitiator materials.

In addition, while less preferred, it will be appreciated that processes as described above may also be carried out without a blocking agent, while still providing dual cure methods and products of the present invention. In addition, while this embodiment has been described primarily with diol and diamine chain extenders, it will be appreciated that chain extenders with more than two reactive groups (polyol and polyamine chain extenders such as triols and triamine chain extenders) may be used to three dimensional objects comprised of a crosslinked thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(ur ethane-urea)).

These materials may be used in bottom-up additive manufacturing techniques such as the continuous liquid interface printing techniques described herein, or other additive manufacturing techniques as noted above and below.

C. Dual hardening polymerizable liquids employing blocked chain extenders and thermally cleavable blocking groups. Another embodiment provides a method of forming a three-dimensional object such as a microfluidic device comprised of polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea), said method comprising:

(b) filling said build region with a polymerizable liquid, said polymerizable liquid comprising a mixture of (i) a polyol and/or polyamine, (U) a blocked or reactive blocked diisocyanate chain extender, (Hi) optionally one or more additional chain extenders, (iv) a photoinitiator, and (v) optionally but in some embodiments preferably a reactive diluent (vi) optionally but in some embodiments preferably a pigment or dye, (vii) optionally but in some embodiments preferably a filler (e.g., silica);

(c) irradiating said build region with light through said optically transparent member to form a solid blocked chain diisocyanate chain extender scaffold from said blocked or reactive blocked diisocyanate chain extender and optionally said reactive diluent and advancing said carrier away from said build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, said three-dimensional object, with said intermediate containing said polyol and/or polyamine and optionally one or more additional chain extenders; and then

(d) heating or microwave irradiating the three-dimensional intermediate sufficiently to form the three-dimensional product comprised of polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)), from the three-dimensional intermediate (e.g., heating or microwave irradiating sufficiently to de-block the blocked diisocyanate chain extender to form an unblocked diisocyanate chain extender that in turn polymerizes with the polyol and/or polyamine and optionally one or more additional chain extenders). In some embodiments, the blocked or reactive blocked diisocyanate chain extender is a compound of the formula A"-X"-A", where X" is a hydrocarbyl group, and each A" is an independently selected substituent of Formula X" :

Formula (X")

where R is a hydrocarbyl group, R' is O or NH, and Z is a blocking group, the blocking group optionally having a reactive terminal group (e.g., a polymerizable end group such as an epoxy, alkene, alkyne, or thiol end group, for example an ethylenically unsaturated end group such as a vinyl ether). In a particular example, each A" is an independently selected substituent of Formula (XI"):

where R and R' are as given above.

Other constituents and steps employed in carrying out these methods may be the same as described in section 9A above.

An example of the preparation of a blocked diol chain extender is shown in the Scheme below.

HO— R'-OH Chain Extender nate

TBAEMA

"Functional Blocking Unit"

Methacrylate Blocked Chain Extender (ABCE)

An example of the preparation of a blocked diamine chain extender is shown in the Scheme below:

H₂ — R'— NH₂ Chain Extender nate

TBAEMA

t "Functional Blocking Unit"

Methacrylate Blocked Chain Extender (ABCE)

An example of a method of the present invention carried out with the materials above is given in FIG. IOC. Without wishing to be bound to any underlying mechanism of the invention, in some embodiments, during thermal cure, (a) the blocked isocyanate-capped chain extender reacts either directly with soft segment and/or chain extender amine or alcohol groups, displacing the blocking agent; or (b) the blocked isocyanate-capped chain extender is cleaved and diisocyanate- capped chain extender is re-formed and reacts with soft segments and additional chain extender if necessary to yield thermoplastic or thermoset polyurethane, polyurea, or copolymer thereof {e.g., poly(urethane-urea)), such as follows:

Soft Segment: Polyamine/Polyol

Segmented Thermoplastic Polyurethane

An alternative mechanism analogous to that described in section B above may also be implemented or employed.

In general, a three-dimensional product of the foregoing methods comprises (i) a linear thermoplastic polyurethane, polyurea, or copolymer thereof {e.g., poly(urethane-urea)), (ii)a cross-linked thermoset polyurethane, polyurea, or copolymer thereof {e.g., poly(urethane-urea)), or (Hi) combinations thereof (optionally blended with de-blocked blocking group which is copolymerized with the reactive diluents(s), for example as an interpenetrating polymer network, a semi-interpenetrating polymer network, or as a sequential interpenetrating polymer network). In some example embodiments, the three-dimensional product may also include unreacted photoinitiator remaining in the three-dimensional formed object. For example, in some embodiments, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of the photoinitiator may remain in the three-dimensional formed object or the photoinitiator may be present in lower amounts or only a trace amount. In some example embodiments, the three- dimensional product may also include reacted photoinitiator fragments. For example, in some embodiments, the reacted photoinitiator fragments may be remnants of the first cure forming the intermediate product. For example, from 0.1 or 0.2 percent by weight to 1, 2 or 4 percent by weight of reacted photoinitiator fragments may remain in the three-dimensional formed object or the reacted photoinitiator fragments may be present in lower amounts or only a trace amount. In example embodiments, a three-dimensional product may comprise, consist of or consist essentially of all or any combination of a linear thermoplastic polyurethane, a cross-linked thermoset polyurethane, unreacted photoinitiator and reacted photoinitiator materials.

In addition, while this embodiment has been described primarily with diol and diamine chain extenders, it will be appreciated that chain extenders with more than two reactive groups (polyol and polyamine chain extenders such as triols and triamine chain extenders) may be used to three dimensional objects comprised of a crosslinked thermoset polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)).

Those skilled in the art will appreciate that systems as described in Ying and Cheng, Hydro lyzable Polyureas Bearing Hindered Urea Bonds, JACS 136, 16974 (2014), may be used in carrying out the methods described herein.

10. Articles comprising interpenetrating polymer networks (IPNs) formed from dual hardening polymerizable liquid systems.

In some embodiments, polymerizable liquids comprising dual hardening systems such as described above are useful in forming three-dimensional articles that in turn comprise interpenetrating polymer networks. This area has been noted by Sperling at Lehigh University and K. C. Frisch at the University of Detroit, and others.

In non-limiting examples, the polymerizable liquid and method steps are selected so that the three-dimensional object comprises the following:

Sol-gel compositions. This may be carried out with an amine (ammonia) permeable window or semipermeable member. In the system discussed here, tetraethyl orthosiliciate (TEOS), epoxy (diglycidyl ether of Bisphenol A), and 4-amino propyl triethoxysilane are be added to a free radical crosslinker and in the process the free radical crosslinker polymerizes and contain the noted reactants which are then reacted in another step or stage. Reaction requires the presence of water and acid. Photoacid generators (PAGs) could optionally be added to the mixture described above to promote the reaction of the silica based network. Note that if only TEOS is included one will end up with a silica (glass) network. One could then increase the temperature to remove the organic phase and be left with a silica structure that would be difficult to prepare by more conventional methods. Many variations (different polymeric structures) can be prepared by this process in addition to epoxies including urethanes, functionalized polyols, silicone rubber etc.

Hydrophobic-hydrophilic IPNs. Prior IPN research contained a number of examples for hydrophobic-hydrophilic networks for improved blood compatibility as well as tissue compatibility for biomedical parts. Poly(hydroxyethyl methacrylate) is a typical example of a hydrophilic component. Another option is to added poly(ethylene oxide) polyols or polyamines with a diisocyanate to produce polyurethane, polyurea, or copolymer thereof {e.g., poly(urethane-urea), incorporated in the reactive system.

Phenolic resins (resoles). Precursors to phenolic resins involve either phenolic resoles (formaldehyde terminal liquid oligomers) or phenolic novolacs (phenol terminal solid oligomers crosslinkable with hexamethyltetraamine). For the present process phenolic resoles can be considered. The viscosity thereof may be high but dilution with alcohols (methanol or ethanol) may be employed. Combination of the phenolic resole with the crosslinkable monomer can then provide a product formed from an IPN. Reaction of the phenolic resole to a phenolic resin can occur above 100 ⁰ in a short time range. One variation of this chemistry would be to carbonize the resultant structure to carbon or graphite. Carbon or graphite foam is typically produced from phenolic foam and used for thermal insulation at high temperatures.

Polyimides. Polyimides based on dianhydrides and diamines are amenable to the present process. In this case the polyimide monomers incorporated into the reactive crosslinkable monomer are reacted to yield an IPN structure. Most of the dianyhdrides employed for polyimides may be crystalline at room temperature but modest amounts of a volatile solvent can allow a liquid phase. Reaction at modest temperatures (e.g., in the range of about 100 °C) is possible to permit polyimide formation after the network is polymerized.

Conductive polymers. The incorporation of aniline and ammonium per sulfate into the polymerizable liquid is used to produce a conductive part. After the reactive system is polymerized and a post treatment with acid (such as HC1 vapor), polymerization to polyaniline can then commence.

Natural product based IPNs. Numerous natural product based IPNs are known based on triglyceride oils such as castor oil. These can be incorporated into the polymerizable liquid along with a diisocyanate. Upon completion of the part the triglycerides can then be reacted with the diisocyanate to form a crosslinked polyurethane. Glycerol can of course also be used.

Sequential IPNs. In this case, the molded crosslinked network are swollen with a monomer and free radical catalyst (peroxide) and optionally crosslinker followed by polymerization. The crosslinked triacylate system should imbide large amounts of styrene, acrylate and/or methacrylate monomers allowing a sequential IPN to be produced.

Polyolefin polymerization. Polyolefm catalysts (e.g. metallocenes) can be added to the crosslinkable reactive system. Upon exposure of the part to pressurized ethylene (or propylene) or a combination (to produce EPR rubber) and temperature in the range of 100 °C, the part can then contain a moderate to substantial amount of the polyolefm. Ethylene, propylene and alpha olefin monomers should easily diffuse into the part to react with the catalyst at this temperature, and as polymerization proceeds more olefin will diffuse to the catalyst site. A large number of parts can be post-polymerized at the same time.

11. Microfluidic fabrication products.

Three-dimensional microfluidic fabrication products such as devices or a portion thereof produced by the methods and processes of the present invention may be final, finished or substantially finished products, or may be intermediate products subject to further manufacturing steps such as surface treatment, laser cutting, electric discharge machining, bonding, etc., is intended. Intermediate products include products for which further additive manufacturing, in the same or a different apparatus, may be carried out. For example, a fault or cleavage line may be introduced deliberately into an ongoing "build" by disrupting, and then reinstating, the gradient of polymerization zone, to terminate one region of the finished product, or simply because a particular region of the finished product or "build" is less fragile than others.

In some embodiments, the microfluidic fabrication product includes a housing configured to accommodate a fluid therein, said housing comprising at least one channel having an average diameter of from 0.1 to 1000 microns {e.g., from 0,1, 0.5, 1, 10, 20, or 50 microns, to 100, 250, 500, 750 or 1000 microns, or any range therein). In some embodiments, the housing includes at least two of said channels in fluid connection with one another. In some embodiments, the housing includes channels in a density of from 1 to 10,000 channels per square millimeter {e.g., a density of from 1, 5, 10, 25 or 50 channels per square millimeter, to 75, 100, 250, 500, 750, 1,000, 5,000, or 10,000 channels per square millimeter, or any range therein). In some embodiments, the housing may include a hard or glassy material. In some embodiments, the housing may include a biodegradable or biocompatible material. In some embodiments, the housing may include a flexible or elastomeric material.

Various microfluidic products having flexible or elastic features can be made at least in part by the methods of the present invention, including, but not limited to, continuous-flow microfluidic devices, droplet-based microfluidic devices, digital microfluidic devices, microarrays or DNA chips, microfluidic devices modeling biological scenarios such as blood flow, evolutionary biology, microbial behavior; optics microfluidic devices, acoustic droplet ejection (ADE) microfluidic devices, microfluidic fuel cells, diagnostic microfluidic devices, and chemistry based microfluidic devices. See, e.g., US Patent No. 6,767,706 to Quake et al.; US Patent No. 7,378,280 to Quake et al.; US Patent No. 7,862,000 to Elizarov et al; US Patent No. 8,168,139 to Manger et al.

The processes described herein can produce microfluidic products with a variety of different properties, including elastomers. Hence in some embodiments the products or portions thereof are rigid; in other embodiments the products or portions thereof are flexible or resilient. In some embodiments, the products have a shape memory (that is, return substantially to a previous shape after being deformed, so long as they are not deformed to the point of structural failure). Particular properties will be determined by factors such as the choice of polymerizable liquid(s) employed.

In some embodiments, the products are unitary (that is, formed of a single type of polymerizable liquid mixture of Part A and Part B); in some embodiments, the products are composites (that is, formed of two or more different polymerizable liquid mixture of independently selected Part A and Part B). In some embodiments, the product or article is a unitary member, meaning it is seamless and/or is not formed by the joining of two or more component pieces. This may be accomplished, e.g., in the subsequent curing of Part B, as noted below.

In some embodiments, the polymerizable liquid mixture contains a dye, pigment or other material therein that blocks or absorbs light at the curing wavelength (e.g., a UV blocking or absorbing pigment), which may serve to limit the cure depth of the resin. Limiting the cure depth of the resin according to some embodiments enhances resolution of the curing for the production of micro-scale features of the microfluidic devices.

In some embodiments, the products are composites that are chemically bonded together. The pieces may be bonded by placing them in contact in an intermediate state and then heating or otherwise reacting the interface to bond the pieces together. The pieces may also be bonded by directly printing one material onto a formed piece made of different material(s). For example, a flexible portion of the microfluidic device may be bonded to a rigid portion in this manner.

In some embodiments, the device comprises one or more seamless microfluidic channels having a curved cross-section segment, including, but not limited to, a lobed or multi-lobed clover (e.g., having three, four, or five curved portions), elliptical, semicircular (e.g., a "D" shape) or circular feature.

In some embodiments, the device comprises a passive micromixer. In a passive micromixer, microchannels are configured to mix the fluid as is passes through, such as through the incorporation of rotations, barriers, multiple splitting, stretching and recombining flows, etc. See, e.g., Lee et al, "Microfluidic Mixing: A Review," Int. J. Mol. Sci. 2011, 12, 3263-3287.

In some embodiments, the device comprises an active micromixer. In an active micromixer, microchannels or other features are configured to move in a way that mixes the fluid therein. For example, a microchannel or chamber may have movable walls or other flexible features therein movable, upon appropriate stimulation, e.g., ultrasonic vibration, electromechanical or mechanical actuators, etc. See, e.g., Yang et al., "Active micromixer for microfluidic systems using lead-zirconate-titanate (PZT)-generated ultrasonic vibration," Electrophoresis 2000, 21(1): 116-119.

In some embodiments, the microfluidic device may include one or more features directly on or in the device, such as a pump (e.g., oscillator, peristaltic), valve or micromixer. See US Patent Publication 2014/0079571 to Hui et al. In some embodiments, such features may advantageously be formed directly on a flexible feature or portion of the device.

In some embodiments, the channels or portions thereof have a smooth wall on their inner surface, i.e., free from perceptible projections, bumps or indentations, such as from a seam formed when constructing a channel by adhering two pieces together, or ridges formed by an additive printing process.

In some embodiments, the device may include or be operatively connected to a microfluidic valve configured to control the flow of fluid through at least one channel. The valve may be formed, e.g., of flexible flaps formed during the fabrication, or they may be added later by insertion into the channel.

In some embodiments, the device may include or be operatively connected to a microfluidic pump configured to mix, meter, recirculate, or agitate a fluid in the housing.

In some embodiments, at least a portion of a channel having an average diameter of from 0.1 to 1000 microns in the product or device extends in a non-linear direction (e.g., having a curved or spiral route); and/or has a tapering cross-section (i.e., the channel diameter increasing or decreasing along the channel). In some embodiments, the tapering along the inside wall of the channel is smooth, i.e., free from perceptible projections, bumps or indentations, such as from a seam formed when constructing a channel by adhering two pieces together, or ridges formed by an additive printing process.

FIG. 11 provides a schematic of a microfluidic device according to some embodiments of the present invention. (Note that the parts are not shown to scale.) The device includes a housing 10 that can accommodate a fluid, with three chambers 30 where samples and/or liquids may be deposited, connected to a winding channel 20 via a tapering portion of the channel 25. The channel has smooth inner walls and a curved, seamless cross-section, such as those shown in FIG. 12.

FIG. 13 is a schematic of a microfluidic device with a housing 10 having channels 20 smoothly branching into a plurality of channels and then reconnecting, akin to a capillary bed. A pump 40 is provided to pump fluid through the channels. The pump 40 may be used with continuous pressure or intermittent pressure (e.g., to mimic a beating heart). One or more valves 50 may be provided in the channel 20, e.g., to promote movement in a particular direction.

FIG. 14 is a schematic showing a microfluidic device with a housing 10 having a inlet . chamber 30 connected to a helical channel 20 by a smoothly tapering section 35.

FIG. 15 is a schematic slice of a housing 10 with a channel 20 showing rounded protrusions or columns 61 therein to provide a passive micromixer 60 which can mix the fluid as it travels through the channel 20. Columns 61 may be formed of the same material of the housing 10, and extend into the void of the channel 20.

FIG. 16 provides a schematic of a microfluidic device according to some embodiments that has a flexible housing 10. The housing 10 has two or more planes of said channels 20 in the z-direction, and the channels of said planes are in a crisscross or grid pattern with respect to each other. In some embodiments, the channels may configured to form a valve 50 where they cross by having a flexible layer between the channels at the cross point which can bend to limit flow through one channel when fluid is provided in the other channel positioned over or under it. See, e.g., Unger et al., "Monolithic Microfabricated Valves ad Pumps by Multilayer Soft Lithography," Science 288:113-116 (2000).

As noted, in some embodiments in which the microfluidic device contains a flexible portion with microchannels therein, the microchannels may include features that act as valves, which valves may be configured to promote the flow of fluid in a determined direction when the housing is flexed by a user. For example, microchannels may comprise a check valve that requires or promotes the flow of fluid (inclusive of a liquid or gas) in a determined direction upon flexing the portion sufficient to move the fluid therein. Examples may include, but are not limited to, a pneumatic valve. Examples may also include a ball check valve, where a ball is placed upstream in a wider portion of the tube, which ball is so dimensioned to fall back to and close the narrower portion of the tube upon flow of fluid in the downstream direction.

Also as noted, microfluidic devices as taught herein may include the incorporation of elastomeric valves. Such valves in the form of multiple planes in the z-direction with microchannels crossing one another (e.g., in a crisscross or grid pattern, optionally with a thin elastomeric layer between layers at the intersections) allow for precise control of complex flow within and enable operations such as pumping, mixing, and sorting. See, e.g., US 2007/0224617 to Maerkl and Quake; Thorsen et al., "Microfluidic Large Scale Integration", Science 298: 580- 584 (2002). In some embodiments, the microfluidic device containing elastomeric valves is unitary and/or is printed as one piece (a unitary member).

In some embodiments, the microfluidic device or a portion thereof is transparent to allow visual monitoring of the flow of a fluid (e.g., a colored liquid) therein.

As noted above, in some embodiments, the microfluidic device includes a macro-to- micro interface therein, e.g., a port or inlet configured to accept a syringe, tube, etc. See, e.g., Fredrickson and Fan, "Macro-to-micro interfaces for microfluidic devices," Miniturisation for Chemistry, Biology & Bioengineering, In some embodiments, the microfluidic device containing a macro-to-micro interface is unitary and/or is printed as one piece (a unitary member).

In some embodiments, microfluidic devices or a portion thereof may be rigid and have, for example, a Young's modulus (MPa) in the range of about 800 to 3500 or any range subsumed therein, a Tensile Strength (MPa) in the range of about 30 to 100 or any range subsumed therein, and/or a percent elongation at break in the range of about 1 to 100 or any range subsumed therein.

In some embodiments, microfluidic devices or a portion thereof may be semi-rigid and have, for example, a Young's modulus (MPa) in the range of about 300 - 2500 or any range subsumed therein, a Tensile Strength (MPa) in the range of about 20 -70 or any range subsumed therein, and/or a percent elongation at break in the range of about 40 to 300 or 600 or any range subsumed therein.

In some embodiments, microfluidic devices or a portion thereof may be elastomeric and have, for example, a Young's modulus (MPa) in the range of about 0.5-40 or any range subsumed therein, a Tensile Strength (MPa) in the range of about 0.5 - 30 or any range subsumed therein, and/or a percent elongation at break in the range of about 50 - 1000 or any range subsumed therein.

In examples provided below are materials for the formation of polyurethane products having a variety of different tensile properties, ranging from elastomeric, to semi-rigid, to flexible, as described above.

12. Alternate methods and apparatus.

Additional examples of apparatus, polymerizable liquids (or "resins"), and methods that may be used in carrying out the present invention include, but are not limited to, those set forth in J. DeSimone et al., Three-Dimensional Printing Using Tiled Light Engines, PCT Publication No. WO/2015/195909 (published 23 Dec. 2015); J. DeSimone et al., Three-Dimensional Printing Method Using Increased Light Intensity and Apparatus Therefore, PCT Publication No. WO/2015/195920 (published 23 Dec. 2015), A. Ermoshkin et al., Three-Dimensional Printing with Reciprocal Feeding of Polymerizable Liquid, PCT Publication No. WO/2015/195924 (published 23 Dec. 2015); J. Rolland et al., Method of Producing Polyurethane Three- Dimensional Objects from Materials having Multiple Mechanisms of Hardening, PCT Publication No. WO 2015/200179 (published 30 Dec. 2015); J. Rolland et al., Methods of Producing Three-Dimensional Objects from Materials Having Multiple Mechanisms of Hardening, PCT Publication No. WO 2015/200173 (published 30 Dec. 2015); J. Rolland et al., Three-Dimensional Objects Produced from Materials Having Multiple Mechanisms of Hardening, PCT Publication No. WO/2015/200189 (published 30 Dec. 2015); J. Rolland et al, Polyurethane Resins Having Multiple Mechanisms of Hardening for Use in Producing Three- Dimensional Objects published 30 Dec. 2015); and J. DeSimone et al., Methods and Apparatus or Continuous Liquid Interface Production with Rotation, PCT Publication No. WO/2016/007495, the disclosures of which are incorporated by reference herein in their entirety.

In an alternate embodiment of the invention, the methods may be carried out with a method and apparatus as described in Hull, US Patent No. 5,236,637, at FIG. 4, where the polymerizable liquid is floated on top of an immiscible liquid layer (said to be "non-wetting" therein). Here, the immiscible liquid layer serves as the build surface. If so implemented, the immiscible liquid (which may be aqueous or non-aqueous) preferably: (i) has a density greater than the polymerizable liquid, (ii) is immiscible with the polymerizable liquid, and (Hi) is wettable with the polymerizable liquid. Ingredients such as surfactants, wetting agents, viscosity- enhancing agents, pigments, and particles may optionally be included in either or both of the polymerizable liquid or immiscible liquid. While the present invention is preferably carried out by continuous liquid interphase/interface polymerization, as described in detail above and in further detail below, in some embodiments alternate methods and apparatus for bottom-up three-dimension fabrication may be used, including layer-by-layer fabrication. Examples of such methods and apparatus include, but are not limited to, those described in U.S. Patent No. 5,236,637 to Hull, US Patent Nos. 5,391 ,072 and 5,529,473 to Lawton, U.S. Patent No. 7,438,846 to John, US Patent No. 7,892,474 to Shkolnik, and U.S. Patent No. 8,1 10,135 to El-Siblani, U.S. Patent Application Publication Nos. 2013/0292862 to Joyce and 2013/0295212 to Chen et al., and PCT Application Publication No. WO 2015/164234 to Robeson et al. The disclosures of these patents and applications are incorporated by reference herein in their entirety.

The present invention is explained in greater detail in the following non-limiting Examples.

EXAMPLE 1

Continuous Fabrication with Intermittent Irradiation and Advancing A process of the present invention is illustrated in FIG. 6, where the vertical axis illustrates the movement of the carrier away from the build surface. In this embodiment, the vertical movement or advancing step (which can be achieved by driving either the carrier or the build surface, preferably the carrier), is continuous and unidirectional, and the irradiating step is carried out continuously. Polymerization of the article being fabricated occurs from a gradient of polymerization, and hence creation of "layer by layer" fault lines within the article is minimized.

An alternate embodiment of the present invention is illustrated in FIG. 7. In this embodiment, the advancing step is carried out in a step-by-step manner, with pauses introduced between active advancing of the carrier and build surface away from one another. In addition, the irradiating step is carried out intermittently, in this case during the pauses in the advancing step. We find that, as long as the inhibitor of polymerization is supplied to the dead zone in an amount sufficient to maintain the dead zone and the adjacent gradient of polymerization during the pauses in irradiation and/or advancing, the gradient of polymerization is maintained, and the formation of layers within the article of manufacture is minimized or avoided. Stated differently, the polymerization is continuous, even though the irradiating and advancing steps are not. Sufficient inhibitor can be supplied by any of a variety of techniques, including but not limited to: utilizing a transparent member that is sufficiently permeable to the inhibitor, enriching the inhibitor (e.g., feeding the inhibitor from an inhibitor-enriched and/or pressurized atmosphere), etc. In general, the more rapid the fabrication of the three-dimensional object (that is, the more rapid the cumulative rate of advancing), the more inhibitor will be required to maintain the dead zone and the adjacent gradient of polymerization.

EXAMPLE 2

Continuous Fabrication with Reciprocation During

Advancing to Enhance Filling of Build Region with Polymerizable Liquid

A still further embodiment of the present invention is illustrated in FIG. 8. As in Example 1 above, this embodiment, the advancing step is carried out in a step-by-step manner, with pauses introduced between active advancing of the carrier and build surface away from one another. Also as in Example 1 above, the irradiating step is carried out intermittently, again during the pauses in the advancing step. In this example, however, the ability to maintain the dead zone and gradient of polymerization during the pauses in advancing and irradiating is taken advantage of by introducing a vertical reciprocation during the pauses in irradiation.

We find that vertical reciprocation (driving the carrier and build surface away from and then back towards one another), particularly during pauses in irradiation, can serve to enhance the filling of the build region with the polymerizable liquid, apparently by pulling polymerizable liquid into the build region. This is advantageous when larger areas are irradiated or larger parts are fabricated, and filling the central portion of the build region may be rate-limiting to an otherwise rapid fabrication.

Reciprocation in the vertical or Z axis can be carried out at any suitable speed in both directions (and the speed need not be the same in both directions), although it is preferred that the speed when reciprocating away is insufficient to cause the formation of gas bubbles in the build region.

While a single cycle of reciprocation is shown during each pause in irradiation in FIG. 23, it will be appreciated that multiple cycles (which may be the same as or different from one another) may be introduced during each pause.

As long as the inhibitor of polymerization is supplied to the dead zone in an amount sufficient to maintain the dead zone and the adjacent gradient of polymerization during the reciprocation, the gradient of polymerization is maintained, the formation of layers within the article of manufacture is minimized or avoided, and the polymerization/fabrication remains continuous, even though the irradiating and advancing steps are not.

EXAMPLE 3

Acceleration during Reciprocation Upstroke and

Deceleration during Reciprocation Downstroke to Enhance Part Quality We observe that there is a limiting speed of upstroke, and corresponding downstroke, which if exceeded causes a deterioration of quality of the part or object being fabricated (possibly due to degradation of soft regions within the gradient of polymerization caused by lateral shear forces a resin flow). To reduce these shear forces and/or enhance the quality of the part being fabricated, we introduce variable rates within the upstroke and downstroke, with gradual acceleration occurring during the upstroke and gradual deceleration occurring during the downstroke, as schematically illustrated in FIG. 9.

EXAMPLE 4

Dual Cure with PEGDA + EGDA + Polvurethane (HMDI based)

5g of the following mixture was mixed for 3 minutes in a high-shear mixer.

lg of poly(ethylene glycol) diacrylate (Mn = 700 g/mol) containing 12wt% of diphenyl(2 4 6-trimethylbenzoyl)phosphine oxide (DPO).

lg of diethyleneglycol diacrylate containing 12wt% DPO

1 g of "Part A" polyurethane resin (Methylene bis(4-Cyclohexylisocyanate) based: "ClearFlex 50" sold by Smooth-On® inc.

2g of "Part B" polyurethane resin (polyol mixture): "ClearFlex 50" sold by Smooth-On® inc.

0.005g of amorphous carbon black powder

After mixing, the resin was 3D printed using an apparatus as described herein. A "honeycomb" object was printed at a speed of 160 mrn/hr using a light intensity setting of 1.2 mV (when measured using a volt meter equipped with a optical sensor). Total printing time was approximately 10 minutes.

After printing, the part was removed from the print stage, rinsed with hexanes, and placed into an oven set at 110°C for 12 hours.

After heating, the part maintained its original shape generated during the initial printing, and it had transformed into a tough, durable, elastomer having an elongation at break around 200%

EXAMPLE 5

Dual Cure with EGDA + Polvurethane (TDI based).

5 g of the following mixture was mixed for 3 minutes in a high-shear mixer.

lg of diethyleneglycol diacrylate containing 12wt% DPO

2 g of "Part A" polyurethane resin (toluene diisocyanate) based: "VytaFlex 30" sold by Smooth-On® inc. 2g of "Part B" polyurethane resin (polyol mixture): "Vytaflex 30" sold by Smooth-On® inc.

After mixing, the resin was 3D printed using an apparatus as described herein. The cylindrical object was printed at a speed of 50 mm/hr using a light intensity setting of 1.2 mV (when measured using a volt meter equipped with an optical sensor). Total printing time was approximately 15 minutes.

After heating, the part maintained its original shape generated during the initial printing, and it had transformed into a tough, durable, elastomer having an elongation at break around 400%.

EXAMPLE 6

Synthesis of a Reactive Blocked Polyurethane Prepolymer for Dual Cure

Add 200 g of melted anhydrous 2000 Da, polytetramethylene oxide (PTM02k) into a 500 mL 3-neck flask charged with an overhead stirrer, nitrogen purge and a thermometer. Then 44.46 g IPDI is added to the flask and stirred to homogeneous solution with the PTMO for 10 min, followed by addition of 140 uL Tin(II) catalyst stannous octoate. Raise the temperature to 70 °C, and keep reaction for 3 h. After 3h, gradually lower the temperature to 40 °C, and gradually add 37.5 g TBAEMA using an additional funnel within 20 min. Then set the temperature to 50 °C and add 100 ppm hydroquinone. Keep the reaction going on for 14 h. Pour out the final liquid as the product.

EXAMPLE 7

Synthesis of a Second Reactive Blocked Polyurethane Prepolymer for Dual Cure

Add 150 g dried 1000 Da, polytetramethylene oxide (PTMOlk) into a 500 mL 3-neck flask charged with an overhead stirrer, nitrogen purge and a thermometer. Then 50.5 g HDI is added to the flask and stirred to homogeneous solution with the PTMO for 10 min, followed by addition of 100 uL Tin(II) catalyst stannous octoate. Raise the temperature to 70 °C, and keep reaction for 3 h. After 3h, gradually lower the temperature to 40 °C, and gradually add 56 g TBAEMA using an additional funnel within 20 min. Then set the temperature to 50 °C and add 100 ppm hydroquinone. Keep the reaction going on for 14 h. Pour out the final liquid as the product.

In the above examples, the PTMO can be replaced by polypropylene glycol (PPG, such as 1000 Da PPG (PPGlk)) or other polyesters or polybuadiene diols. IPDI or HDI can be replaced by other diisocyanates. The molar stoichiometry of the polyol : diisocyanate : TBAEMA is preferably 1 : 2 : 2. Preferably use 0.1 - 0.3 wt% stannous octoate to the weight of the polyol.

EXAMPLE 8

Printing and Thermal Curing with a Reactive Blocked Polyurethane Prepolymers

ABPU resins can be printed (optionally but preferably by continuous liquid interphase/interface printing) at up to 100 mm/hr using the formulations in Table 1 to generate elastomers with low hysteresis after thermally cured at 100 °C for 2 to 6 hours, depending on the diisocyanates used in ABPU and the chain extender(s).

Table 1

Parts by weight

ABPU 320

Reactive Diluent 40-80

Ethylene glycol 8-20

H12MDA 8-20

PPO 1-4

Dog-bone-shaped specimens were printed by continuous liquid interface printing with different ABPUs (varying the diisocyanate and polyol used for the synthesis) and reactive diluents. Table 2 shows the mechanical properties of some of the thermally cured dog-bone samples at room temperature.

Table 2

ABPU Reactive diluent Tensile stress at % elongation at

Diisocyanate Polyol maximum load break

(MPa)

IPDI PTM02k Methyl 25 650

methacrylate

IPDI PPGlk Cyclohexane 7.5 368

methacrylate

MDI PTM02k TBAEMA 13.4 745

HDI PTMOlk TBAEMA 13 490

HMDI PTMOlk TBAEMA 13.6 334

EXAMPLES 9-52

Additional Polyurethane Dual Cure Materials, Testing and Tensile Properties

The following abbreviations are used in the Examples below: "DEGMA" means di(ethylene glycol) methyl ether methacrylate; "IBMA" means isoboronyl methacrylate; "PACM" means 4,4'-Diaminodicyclohexyl methane; "BDO" means 1,4-butanediol; "PPO" means Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide; "MDEA" means 4,4'-methylene-bis-(2,6- diethylaniline); "2-EHMA" means 2-ethylhexyl methacrylate; and "PEGDMA" means poly(ethylene glycol) dimethacrylate (MW = 700 Da).

EXAMPLE 9

Testing of Tensile Properties

In the examples above and below, tensile properties were tested in accordance with ASTM standard D638-10, Standard Test Methods for Tensile Properties of Plastics (ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA, 19428-2959 USA).

Briefly, tensile specimens (sometimes referred to as "dog-bone samples" in reference to their shape), were loaded onto an Instron 5964 testing apparatus with Instron BLUEHILL3 measurement software (Instron, 825 University Ave, Norwood, MA, 02062-2643, USA). The samples are oriented vertically and parallel to the direction of testing. Cast and flood cured samples were fully cured using a DNMAX 5000 EC-Series enclosed UV flood lamp (225 mW/cm²) for from thirty to ninety seconds of exposure. Table 3 below summarizes the types of tensile specimens tested, general material property (rigid or non-rigid), and the associated strain rate.

Table 3

Dogbone Type MaterialType Strain Rate

(mm/min)

IV Rigid 5

V Rigid 1

IV Non-rigid 50

V Non-rigid 10

Dogbone type IV is used to test elastomeric samples.

The samples were tested at a rate such that the sample ruptures at a time between 30 seconds to 5 minutes to ensure that sample strain rate is slow enough to capture plastic deformation in the samples.

Measured dogbone samples that do not rupture in the middle rectangular section are excluded. Samples that break in the grips or prior to testing are not representative of the anticipated failure modes and are excluded from the data.

Persuant to ASTM D-638, measure the Young's modulus (modulus of elasticity) (slope of the stress-strain plot between 5-10% elongation), tensile strength at break, tensile strength at yield, percent elongation at break, percent elongation at yield.

A strain rate is chosen such that the part with the lowest strain-at-break (%) will fail within 5 minutes. This often means that a slower strain rate will be necessary for rigid samples. EXAMPLE 10

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Components as shown in Table 4, except PACM, were added to a container and thoroughly mixed (either by an overhead stirrer or a centrifugation mixer such as THINKY(TM) mixer) to obtain a homogeneous resin. Then PACM was added to the resin and mixed for another 2-30 min depending on the volume and viscosity of resin. The resin was printed by CLIP as described above into D638 Type IV dog-bone-shaped specimens followed by thermal curing at 125 °C for 2h. The cured elastomer specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are also summarized in Table 4.

Table 4

Parts by

weight

ABPU(PTM01k+HDI+TBAEMA) 697

DEGMA 82

IBMA 123

PACM 83

PPO 5_

Tensile Strength (MPa) 13.1

% Elongation at Break 395

EXAMPLE 11

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 19 but using the formulation in Table 5. The cured specimens were tested following ASTM standard on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 5.

Table 5

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 721

DEGMA 84

IBMA 126

PACM 54

PPO 5_

Tensile Strength (MPa) 26.8

% Elongation at Break 515 EXAMPLE 12

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 19 but using the formulation in Table 6. The cured specimens were tested following ASTM standard on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 6.

Table 6

Parts by

weight

ABPU(PTM02k+HMDI+TBAEMA) 728

DEGMA 86

IBMA 128

PACM 53

PPO 5_

Tensile Strength (MPa) 23.1

% Elongation at Break 456

EXAMPLE 13

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Components as shown in Table 7 were added to a container and thoroughly mixed (either by an overhead stirrer or a centrifugation mixer such as THINKY(TM) mixer) to obtain a homogeneous resin. The resin was casted into a square mold (with dimensions of 100x 100x4 mm), and UV flood cured for lmin, followed by thermal curing at 125 °C for 2h. The obtained elastomer sheet was die-cut into rectangular bars with dimensions of 100x20x4 mm. The elastomer specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 7.

Table 7

Parts by

weight

ABPU(PTMO 1 k+HDI+TB AEM A) 666

2-EHMA 131

IBMA 66

MDEA 123

PPO 10_

Tensile Strength (MPa) 14.4

% Elongation at Break 370

EXAMPLE 14

Elastomer from a Reactive Blocked Polyurethane Prepolymer Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 8. The elastomer specimens were tested following ASTM standard D638- 10 an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 8.

Table 8

Parts by

weight

ABPU(PTM01k+HDI+TBAEMA) 692

DEGMA 102

2-EHMA 102

PEGDMA 14

PACM 80

PPO 10_

Tensile Strength (MPa) 6.42

% Elongation at Break 388

EXAMPLE 15

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 9. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 9.

Table 9

Parts by

weight

ABPU(PTMO 1 k+IPDI+TB AEM A) 700

DEGMA 206

PEGDMA 10

PACM 74

PPO 10_

Tensile Strength (MPa) 11.26

% Elongation at Break 366

EXAMPLE 16

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 10. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 10. Table 10

Parts by

weight

ABPU(PTM01k+MDI+TBAEMA) 672

2-EHMA 248

PEGDMA 10

PACM 60

PPO 10_

Tensile Strength (MPa) 24.93

% Elongation at Break 320

EXAMPLE 17

Elastomer from a Reactive Blocked Polvurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 11. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 11.

Table 11

Parts by

weight

ABPU(PTMO 1 k+MDI+TB AEM A) 698

DEGMA 208

PEGDMA 10

PACM 74

PPO 10

Tensile Strength (MPa) 20.14

% Elongation at Break 355

EXAMPLE 18

Elastomer from a Reactive Blocked Polvurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 12. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 12.

Table 12

Parts by

weight

ABPU(PTM02k+HMDI+TBAEMA) 2000

DEGMA 400

2-EHMA 200

PEGDMA 66 PACM 145

PPO 14_

Tensile Strength (MPa) 16.7

% Elongation at Break 476

EXAMPLE 19

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Tablel3. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 13.

Table 13

Parts by

weight

ABPU(PTM02k+HMDI+TBAEMA) 2000

DEGMA 400

2-EHMA 200

PACM 145

PPO 14_

Tensile Strength (MPa) 16.9

% Elongation at Break 499

Example 20

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 14 by mixing all the components together. The elastomer specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 14.

Table 14

Parts by

weight

ABPU(PTM02k+HMDI+TBAEMA) 2000

DEGMA 400

2-EHMA 200

PEGDMA 66

BDO 62

PPO* 14 _

Tensile Strength (MPa) 2.14

% Elongation at Break 188 EXAMPLE 21

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 15. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 15.

Table 15

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2000

DEGMA 420

2-EHMA 180

PEGDMA 67

PACM 149

PPO 14_

Tensile Strength (MPa) 8.37

% Elongation at Break 386

EXAMPLE 22

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 16. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 16.

Table 16

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2400

2-EHMA 700

PACM 179

PPO 16_

Tensile Strength (MPa) 17.2

% Elongation at Break 557

EXAMPLE 23

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 17. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 17.

Table 17

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2400

2-EHMA 630

PEGDMA 70

PACM 179

PPO 16_

Tensile Strength (MPa) 13.4

% Elongation at Break 520

EXAMPLE 24

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 18. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 18.

Table 18

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2000

DEGMA 400

2-EHMA 200

PACM 149

PPO 14

Tensile Strength (MPa) 13.6

% Elongation at Break 529

EXAMPLE 25

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 19. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 19. Table 19

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2000

DEGMA 500

2-EHMA 500

PACM 149

PPO 14_

Tensile Strength (MPa) 9.32

% Elongation at Break 485

EXAMPLE 26

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 20. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 20.

Table 17

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2000

DEGMA 650

2-EHMA 750

PACM 149

PPO 14_

Tensile Strength (MPa) 5.14

% Elongation at Break 440

EXAMPLE 27

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 21. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 21.

Table 21

Parts by

weight

ABPU(PTMO 1 k+HDI+TB AEMA) 2000

DEGMA 580

PACM 246

PPO 14_

Tensile Strength (MPa) 6.48 % Elongation at Break 399

EXAMPLE 28

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 22. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 22.

Table 22

Parts by

weight

ABPU(PTMO 1 k+HDI+TB AEMA) 2000

DEGMA 580

PEGDMA 60

PACM 246

PPO 14_

Tensile Strength (MPa) 6.49

% Elongation at Break 353

EXAMPLE 29

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 23. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 23.

Table 23

Parts by

weight

ABPU(PTM01k+HDI+TBAEMA) 2000

DEGMA 620

2-EHMA 180

PACM 246

PPO 14_

Tensile Strength (MPa) 6.83

% Elongation at Break 415

EXAMPLE 30

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 24. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 24.

Table 24

Parts by

weight

ABPU(PTM02k+HMDI+TBAEMA) 2000

DEGMA 400

2-EHMA 200

PEGDMA 66

PACM 145

PPO 14

Tensile Strength (MPa) 15.6

% Elongation at Break 523

EXAMPLE 31

Elastomer from a Reactive Blocked Polyurethane Prepolymer

Cured elastomer specimens were prepared in the same manner as in Example 22 but using the formulation in Table 25. The elastomer specimens were tested following ASTM standard D638- 10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 25.

Table 25

Parts by

weight

ABPU(PTM02k+IPDI+TBAEMA) 2000

DEGMA 420

2-EHMA 180

PEGDMA 67

PACM 149

PPO 14_

Tensile Strength (MPa) 13.2

% Elongation at Break 480

EXAMPLE 32

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Components as shown in Table 26, except PACM, were added to a container and thoroughly mixed (either by an overhead stirrer or THINKY(TM) mixer) to obtain a homogeneous resin. Then PACM was added to the resin and mixed for another 30 min. The resin was cast into dog- bone-shaped specimens by UV flood cure for 60 seconds followed by thermal curing at 125 °C for 4h. The cured specimens were tested following ASTM standard on an Instron apparatus for mechanical properties as described above, which properties are also summarized in Table 26. Table 26

Component Weight %

ABPU ABPU-1K-MDI 61.78

Reactive Diluent IBM A 30.89

Chain Extender PACM 6.56

Initiator PPO 0.77

Tensile Strength (MPa) 31.7

Modulus (MPa) 680

Elongation (%) 273

EXAMPLE 33

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 27. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 27.

Table 27

Component Weight %

ABPU ABPU-1K-MDI 53.51

Reactive Diluent IBMA 40.13

Chain Extender PACM 5.69

Initiator PPO 0.67

Tensile Strength (MPa) 26.2

Modulus (MPa) 1020

Elongation (%) 176

EXAMPLE 34

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 28. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 28.

Table 28

Component Weight %

ABPU ABPU-1K-MDI 47.2

Reactive Diluent IBMA 47.2

Chain Extender PACM 5.01 Initiator PPO 0.59

Tensile Strength (MPa) 29.5

Modulus (MPa) 1270

Elongation (%) 3.21

EXAMPLE 35

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 29. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 29.

Table 29

Component Weight %

ABPU ABPU-1K-MDI 42.22

Reactive Diluent IBMA 52.77

Chain Extender PACM 4.49

Initiator PPO 0.53

Tensile Strength (MPa) 19.3

Modulus (MPa) 1490

Elongation (%) 1.42

EXAMPLE 36

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 30. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 30.

Table 30

Component Weight %

ABPU ABPU-1K-MDI 61.13

Reactive Diluent IBMA 30.57

Chain Extender PACM 7.54

Initiator PPO 0.76

Tensile Strength (MPa) 19.3

Modulus (MPa) 1490

Elongation (%) 1.42 EXAMPLE 37

Dual-Cure Material from Reactive Blocked Polvurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 31. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 31.

Table 31

Component Weight %

ABPU ABPU-1K-MDI 61.55

Reactive Diluent IBMA 30.78

Chain Extender P ACM 6.9

Initiator PPO 0.77

Tensile Strength (MPa) 34.1

Modulus (MPa) 713

Elongation (%) 269

EXAMPLE 38

Dual-Cure Material from Reactive Blocked Polvurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 32. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 32.

Table 32

Component Weight %

ABPU ABPU-1K-MDI 61.98

Reactive Diluent IBMA 30.99

Chain Extender PACM 6.25

Initiator PPO 0.77

Tensile Strength (MPa) 39.7

Modulus (MPa) 664

Elongation (%) 277

EXAMPLE 39

Dual-Cure Material from Reactive Blocked Polvurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 33. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 33.

Table 33

Component Weight %

ABPU ABPU-1K-MDI 63.75

Reactive Diluent IBMA 31.87

Chain Extender PACM 3.59

Initiator PPO 0.8

Tensile Strength (MPa) 21.3

Modulus (MPa) 265

Elongation (%) 207 EXAMPLE 40

Dual-Cure Material from Reactive Blocked Polvurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 34. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 34.

Table 35

Component Weight %

ABPU ABPU-1K-MDI 63.75

Reactive Diluent IBMA 31.87

Chain Extender PACM 5.02

Initiator PPO 0.8

Tensile Strength (MPa) 22.7

Modulus (MPa) 312

Elongation (%) 211

EXAMPLE 41

Dual-Cure Material from Reactive Blocked Polvurethane Prepolymer Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 36. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 36.

Table 36

Component Weight %

ABPU ABPU-1K-MDI 63.75 Reactive Diluent IBMA 31.87

Chain Extender PACM 5.71

Initiator PPO 0.8

Tensile Strength (MPa) 28.4

Modulus (MPa) 407

Elongation (%) 222

EXAMPLE 42

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 37. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 37.

Table 37

Component Weight %

ABPU ABPU-1K-MDI 63.03

Reactive Diluent IBMA 31.51

Chain Extender BAMN 4.67

Initiator PPO 0.79

Tensile Strength (MPa) 25.1

Modulus (MPa) 155

Elongation (%) 297 EXAMPLE 43

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 38. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 38.

Table 38

Component Weight %

ABPU ABPU-1K-MDI 63.03

Reactive Diluent IBMA 31.35

Chain Extender BAMN 5.2

Initiator PPO 0.79

Tensile Strength (MPa) 21.7

Modulus (MPa) 214 Elongation (%) 291

EXAMPLE 44

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 39. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 39.

Table 39

Component Weight %

ABPU-650-

ABPU HMDI 52.62

Reactive Diluent IBMA 39.47

Chain Extender PACM 7.26

Initiator PPO 0.66

Tensile Strength (MPa) 31.7

Modulus (MPa) 1460

Elongation (%) 3.65 EXAMPLE 45

Dual-Cure Material from Reactive Blocked Polyurethane Prepolymer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 40. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 40.

Table 40

Component Weight %

ABPU-650-

ABPU HMDI 60.6

Reactive Diluent IBMA 30.29

Chain Extender PACM 8.36

Initiator PPO 0.76

Tensile Strength (MPa) 29.4

Modulus (MPa) 864

Elongation (%) 191 EXAMPLE 46

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 41. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 41.

Table 41

Component Weight %

ABPU-650-

ABPU HMDI 30.53

ABPU ABPU-1K-MDI 30.53

Reactive Diluent IBMA 30.53

Chain Extender PACM 7.63

Initiator PPO 0.76

Tensile Strength (MPa) 29.1

Modulus (MPa) 492

Elongation (%) 220

EXAMPLE 47

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 42. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 42.

Table 42

Component Weight %

ABPU-650-

ABPU HMDI 54.6

Reactive Diluent IBMA 27.6

Crosslinker DUDMA 9.9

Chain Extender PACM 7.1

Initiator PPO 0.8

Tensile Strength (MPa) 59.3

Modulus (MPa) 1880

Elongation (%) 91 EXAMPLE 48

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 43. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 43.

Table 43

Component Weight %

ABPU-650-

ABPU HMDI 54.6

Reactive Diluent IB MA 18.8

Reactive Diluent PEMA 18.8

Chain Extender PACM 7.1

Initiator PPO 0.8

Tensile Strength (MPa) 32.5

Modulus (MPa) 1050

Elongation (%) 178

EXAMPLE 49

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 44. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 44.

Table 44

Component Weight %

ABPU PTMO-1K-MDI 53.6

Reactive Diluent IB MA 23.1

Reactive Diluent PEMA 7.1

Crosslinker DUDMA 9.7

Chain Extender PACM 5.7

Initiator PPO 0.8

Tensile Strength (MPa) 43.8

Modulus (MPa) 1030

Elongation (%) 135 EXAMPLE 50

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Cured specimens were prepared in the same manner as in Example 41 but using the formulation in Table 45. The specimens were tested following ASTM standard D638-10 on an Instron apparatus for mechanical properties as described above, which properties are summarized in Table 45.

Table 45

Component Weight %

PTMO-650-

ABPU HMDI 55.1

Reactive Diluent IBMA 33.1

Crosslinker BPADMA 3.7

Chain Extender PACM 7.2

Initiator PPO 0.9

Tensile Strength (MPa) 33

Modulus (MPa) 1390

Elongation (%) 57

EXAMPLE 51

Dual-Cure Material from Reactive Blocked Polyurethane Prepolvmer

Table 30

Component Weight %

PTMO-650-

ABPU HMDI 52.6

Reactive Diluent IBMA 14.9

Reactive Diluent PEMA 5.0

Crosslinker SR239 19.9

Chain Extender PACM 6.9

Initiator PPO 0.8

Tensile Strength (MPa) 44.5

Modulus (MPa) 1520

Elongation (%) 12.4

EXAMPLE 52

Representative Polyurethane Products Produced from Dual-Cure Material

Polymerizable materials as described in the examples, or detailed description, above (or variations thereof that will be apparent to those skilled in the art) provide products with a range of different elastic properties. Examples of those ranges of properties, from rigid, through semirigid (rigid and flexible), to elastomeric. Particular types of products that can be made from such materials include but are not limited to those given in the table below. The products may contain reacted photoinitiator fragments (remnants of the first cure forming the intermediate product) when produced by some embodiments of methods as described above. It will be appreciated that the properties may be further adjusted by inclusion of additional materials such as fillers and/or dyes, as discussed above.

EXAMPLE 53

Fabrication of Microfluidic Device

A flexible housing containing one or more microfluidic channels is printed as taught hereinabove, with a feature resolution below 100 microns. See, e.g., J. Tumbleston et al, Continuous liquid interface production of 3D Objects, Science 347, 1349-1352 (published online 16 March 2015).

The foregoing is illustrative of the present invention, and is not to be construed as limiting thereof. The invention is defined by the following claims, with equivalents of the claims to be included therein.

Claims

THAT WHICH IS CLAIMED IS:

1. A microfluidic device comprising:

(a) a housing configured to accommodate a fluid therein, said housing comprising at least one seamless channel having a curved cross-section segment, wherein (i) at least a portion of said channel extends in a non-linear direction; and/or has a tapering cross-section, (ii) wherein at least a portion of said channel has an average diameter of from 0.1 to 1000 microns, and/or (Hi) wherein at least a portion of said device is flexible; and

(b) optionally, an actuator operably associated therewith.

2. The device of claim 1, wherein said housing comprises a semi-rigid or elastomeric material.

3. The device of claim 1, wherein said channel comprises a lobed, elliptical, semicircular or circular cross-section segment, or a combination thereof.

4. The device of claim 1 or claim 2, wherein said housing comprises at least two of said channels, optionally wherein at least two of said channels are in fluid connection with one another, and optionally wherein said housing comprises said channels in a density of 1-10,000 channels per square millimeter.

5. The device of any preceding claim, wherein said device comprises two or more planes of said channels in the z-direction and wherein said channels of said planes are in a crisscross or grid pattern with respect to each other, and optionally wherein said channels are configured to form a valve where they cross.

6. The device of any preceding claim, wherein said housing is configured to form a passive micromixer.

7. The device of any preceding claim, wherein said housing is configured to form an active micromixer.

8. The device of any preceding claim, wherein said device further comprises a microfluidic valve formed therein and configured to control the flow of fluid through said at least one channel.

9. The device of claim 8, wherein said valve is a check valve.

10. The device of claim 8, wherein said valve is a pneumatic valve.

11. The device of any preceding claim, wherein said device further comprises a microfluidic pump configured to mix, meter, recirculate, or agitate a fluid in the housing, and optionally wherein said microfluidic pump is directly on or in said housing.

12. The device of any preceding claim, wherein said housing comprises a biodegradable or biocompatible material.

13. The device of any preceding claim, wherein said one or more channels comprises an inner surface, said inner surface comprising a smooth wall.

14. The device of any preceding claim, wherein said housing further comprises a chamber configured to contain a fluid therein, said chamber in seamless fluid connection with said one or more channels, wherein at least a portion of said chamber has an average diameter of from 0.1 to 1000 millimeters.

15. The device of any preceding claims wherein said housing further comprises a macro- to-micro interface therein.

16. The device of any preceding claim, wherein said housing is unitary.

17. The device of any preceding claim, wherein said housing is formed of a single, unitary member.

18. The device of any preceding claim, wherein said housing is flexible.

19. The device of any preceding claim, wherein said device is: a continuous-flow microfluidic device, a droplet-based microfluidic device, a digital microfluidic device, a microarray or DNA chip, a microfluidic device modeling biological scenarios such as blood flow, evolutionary biology, microbial behavior, an optics microfluidic device, an acoustic droplet ejection (ADE) microfluidic device, a microfluidic fuel cell, a diagnostic microfluidic device, or a chemistry based microfluidic device; or

wherein said device is: an inkjet printhead, lab-on-a-chip device such as a sensor, single- molecule assay, molecular assay, biological assay, or drug discovery platform, a micro- propulsion device, a micro-thermal device, a synthetic tissue scaffold, a biological organ, or a synthetic organ or portion thereof on a chip.

20. A method of forming a microfluidic device or portion thereof of any one of claims 1- 19, the method comprising the steps of:

(b) filling said build region with a polymerizable liquid, said polymerizable liquid comprising a mixture of (i) a light polymerizable liquid first component, and (ii) a second solidifiable component different from said first component, and optionally, (Hi) a dye, pigment or other material dispersed therein that blocks or absorbs light at the curing wavelength;

(c) forming a three-dimensional intermediate from said polymerizable liquid, where said intermediate has the shape of, or a shape to be imparted to, said three-dimensional object, and where said polymerizable liquid is solidified by exposure to light;

(d) optionally washing the three-dimensional intermediate, and then

(e) heating and/or microwave irradiating said build region with light through said optically transparent member to form a solid polymer scaffold from said first component and also advancing said carrier away from said build surface to form a three-dimensional intermediate having the same shape as, or a shape to be imparted to, said microfluidic device and containing said second solidifiable component carried in said scaffold in unsolidified and/or uncured form; and

(f) concurrently with or subsequent to said irradiating step, solidifying and/or curing said second solidifiable component in said three-dimensional intermediate to form said microfluidic device or portion thereof.

21. The method of claim 20, wherein said forming step is carried out by additive manufacturing (e.g., bottom-up or top-down three-dimensional fabrication). _r

22. The method of claim 20, wherein said forming step is carried out by: (i) by either bottom-up three dimensional fabrication between a carrier and a build surface or top-down three dimensional fabrication between a carrier and a fill level, the fill level optionally defined by a build surface; and/or

(ii) optionally with a stationary build surface; and/or

(Hi) optionally while maintaining the resin in liquid contact with both the intermediate object and the build surface, and/or

(iv) optionally with said forming step carried out in a layerless manner,

each during the formation of at least a portion of the three dimensional intermediate.

23. The method of claim 20 to 22, wherein said forming step is carried out by continuous liquid interface production (CLIP).

24. The method of claim 20 to 23, wherein said second component comprises:

a polymerizable liquid solubilized in or suspended in said first component;

a polymerizable solid solubilized in said first component; or

a polymer solubilized in said first component.

25. The method of claim 20 to 23, wherein said second component comprises:

a polymerizable solid suspended in said first component;

solid thermoplastic polymer particles suspended in said first component.

26. The method of any one of claims 20-25, wherein said three-dimensional intermediate is collapsible or compressible.

27. The method of any one of claims 20-26, wherein said microfluidic device comprises a polymer blend formed from said first component and said second component.

28. The method of any one of claims 20-27, wherein said polymerizable liquid comprises:

from 1, 2 or 5 percent by weight to 20, 30 or 40 percent by weight of said first component; and

from 60, 70 or 80 percent by weight to 95, 98 or 99 percent by weight of said second component.

29. The method of any one of claims 20-28, wherein said solidifying and/or curing step (d) is carried out concurrently with said irradiating step (c) and:

said solidifying and/or curing step is carried out by precipitation;

said irradiating step generates heat from the polymerization of said first component in an amount sufficient to thermally solidify or polymerize said second component; and/or

said second component is solidified by the same light as is said first component in said irradiating step.

30. The method of any one of claims 20-28, wherein said solidifying and/or curing step (d) is carried out subsequent to said irradiating step (c) and is carried out by:

heating said second solidifiable component;

irradiating said second solidifiable component with light at a wavelength different from that of the light in said irradiating step (c);

contacting said second polymerizable component to water; and/or

contacting said second polymerizable component to a catalyst.

31. The method of any one of claims 20-28, wherein said second component comprises a polyurethane, polyurea, or copolymer thereof, a silicone resin, or natural rubber, and said solidifying step is carried out by heating.

32. The method of any one of claims 20-28, wherein said second component comprises a cationically cured resin and said solidifying and/or curing step is carried out irradiating said second solidifiable component with light at a wavelength different from that of the light in said irradiating step (c).

33. The method of any one of claims 20-28, wherein:

said second component comprises a polyurethane, polyurea, or copolymer thereof, and said solidifying and/or curing step is carried out by contacting said second component to water.

34. The method of any one of claims 20-28, wherein:

said solidifying and/or curing step (d) is carried out subsequent to said irradiating step; and said solidifying and/or curing step (d) is carried out under conditions in which said solid polymer scaffold degrades and forms a constituent necessary for the polymerization of said second component.

35. The method of any one of claims 20-28, wherein:

said second component comprises a polyurethane, polyurea, or copolymer thereof, a silicone resin, a ring-opening metathesis polymerization resin, or a click chemistry resin, and said solidifying and/or curing step is carried out by contacting said second component to a polymerization catalyst.

36. The method of any one of claims 20-35, wherein said irradiating and/or said advancing steps are carried out while also concurrently:

(i) continuously maintaining a dead zone of polymerizable liquid in contact with said build surface, and

(ii) continuously maintaining a gradient of polymerization zone between said dead zone and said solid polymer and in contact with each thereof, said gradient of polymerization zone comprising said first component in partially cured form.

37. The method of claim 36, wherein said optically transparent member comprises a semipermeable member, and said continuously maintaining a dead zone is carried out by feeding an inhibitor of polymerization through said optically transparent member, thereby creating a gradient of inhibitor in said dead zone and optionally in at least a portion of said gradient of polymerization zone.

38. The method of any one of claims 20-37, wherein said optically transparent member is comprised of a semipermeable fluoropolymer, a rigid gas-permeable polymer, porous glass, or a combination thereof.

39. The method of any one of claims 20-38, wherein:

said first component comprises a free radical polymerizable liquid and said inhibitor comprises oxygen; or

said first component comprises an acid-catalyzed or cationically polymerizable liquid, and said inhibitor comprises a base.

40. The method of any one of claims 20-39, wherein said irradiating step is carried out by maskless photolithography.

41. The method of any one of claims 20-40, wherein said irradiating step is carried out with a two-dimensional radiation pattern projected into said build region, wherein said pattern varies over time while said advancing continues for a time sufficient to form said three- dimensional object.

42. The method of any one of claims 20-41, wherein said gradient of polymerization zone and said dead zone together have a thickness of from 1 to 1000 microns.

43. The method of any one of claims 20-42, wherein said gradient of polymerization zone is maintained for a time of at least 5, 10, 20 or 30 seconds, or at least 1 or 2 minutes.

44. The method of any one of claims 20-43, wherein said advancing is carried out at a cumulative rate of at least 0.1, 1, 10, 100 or 1000 microns per second.

45. The method of any one of claims 20-44, wherein the build surface is substantially fixed or stationary in the lateral and/or vertical dimensions.

46. The method of any one of claims 20-45, further comprising vertically reciprocating said carrier with respect to the build surface to enhance or speed the refilling of the build region with the polymerizable liquid.

47. The method of any one of claims 20-46, wherein said microfluidic device comprises a macro-to-micro interface therein and said microfluidic device comprising said macro-to-micro interface is formed as one piece.

48. A microfluidic device or method of forming substantially as described herein above and/or for use in carrying out a method of any preceding claim.