The present disclosure generally relates to forming microfluidic chips through hot embossing, and, more particularly, a novel hot embossing process using a three-dimensional (“3D”) printed microfeature mold.
Lab-on-chip technologies use microfluidics and electronics to scale down complicated laboratory processes into single devices, often smaller than a credit card. The miniaturization and automation afforded by these microfluidic chips has the potential to both decrease the cost and increase the reliability of point-of-care testing, DNA/RNA analysis, diagnostics, drug development, and many other fields, all of which play a significant role in understanding human health. While these lab-on-chip devices have many benefits for end users, the technology development process can be challenging and expensive. In particular, the manufacture of microfluidic prototypes is a major pain point for researchers. Accordingly, it may be desirable to develop a method of forming lab-on-chip devices that addresses the shortcomings of existing fabrication techniques.
The present disclosure provides components, systems and methods for forming microfeatures in a chip. A microfeature mold may be formed from a thermally stable photopolymer using a three-dimensional (3D) printing process. The microfeature mold may include a first half having a cavity alignment feature and a recess and a second half having a microfeature pattern and a core alignment feature. A thermoplastic sheet may be placed within the recess. The thermoplastic sheet may be compressed between the first half and the second half of the microfeature mold using a compression apparatus. One or more of the first half of the microfeature mold and the second half of the microfeature mold may be heated to a temperature above the glass transition temperature of the thermoplastic sheet, thereby causing the compressed thermoplastic sheet to flow and one or more microfeatures to be formed.
A system for forming microfeatures on a microfluidic chip may include a microfeature mold comprising a three-dimensional printed thermally stable photopolymer. A first half of the microfeature mold may include a recess and a cavity alignment feature. The recess may be configured to hold a thermoplastic sheet. A second half of the microfeature mold may include a microfeature pattern and a core alignment feature, the core alignment feature aligned with the cavity alignment feature. A compression apparatus may be coupled to one or more of the first half of the microfeature mold and the second half of the microfeature mold.
A method of forming microfeatures in a chip may include positioning a thermoplastic sheet within a recess of a first half of a microfeature mold. The microfeature mold may comprise a three-dimensional printed thermally stable photopolymer. A cavity alignment feature of the first half of the microfeature mold may be aligned with a core alignment feature of a second half of the microfeature mold. The thermoplastic sheet may be compressed, via a compression apparatus, between the first half of the microfeature mold and the second half of the microfeature mold, such that a microfeature pattern of the second half of the microfeature mold is imprinted on the thermoplastic sheet. One or more of the first half of the microfeature mold and the second half of the microfeature mold may be heated to a temperature above the glass transition temperature of the thermoplastic sheet, such that the compressed thermoplastic sheet flows within the microfeature pattern.
A three-dimensional printing method of forming a microfeature mold may include lowering a build platform into a resin tank containing a liquid photopolymer resin, such that the liquid photopolymer resin fills a predetermined gap between a transparent bottom plate of the resin tank and the build platform. A light may be emitted from an optical curing source below the transparent bottom plate in a first pattern based on a predetermined design to cure the liquid photopolymer resin and form a first layer of the microfeature mold. The first layer may comprise a thermally stable photopolymer. The build platform may be raised with respect to the transparent bottom plate, such that the liquid photopolymer resin fills a gap between the transparent bottom plate and the first layer of the microfeature mold. The light may be emitted from the optical curing source in a second pattern based on the predetermined design to cure the liquid photopolymer resin to and form a second layer of the microfeature mold. The second layer may also comprise the thermally stable photopolymer. The raising and emitting steps may be repeated until the microfeature mold is fully formed.
The drawings described below are for illustration purposes only. The drawings are not intended to limit the scope of the present disclosure.
The present disclosure is related to forming microfluidic chips through hot embossing, and, more particularly, a novel hot embossing process using a three-dimensional (“3D”) printed microfeature mold that addresses the shortcomings of existing fabrication techniques. The methods, systems, and apparatuses disclosed herein may be used to create custom thermoplastic microfluidic devices, which can be used to conduct a variety of scientific tasks useful in industries including biotech, pharmaceuticals, and diagnostics.
Lab-on-chip companies typically use one or more of the following methods for fabricating chips: soft lithography, lamination, micromachining, injection molding, and hot embossing. As described below, these processes may be cost-prohibitive and may require weeks to months of time for manufacturing, making it difficult to rapidly generate new chips or alter existing designs.
Soft lithography is a process of assembling microfluidic devices that includes techniques similar to those used in semiconductor fabrication. In a typical process, a layer of photoresist (e.g., SU-8) may be formed on a silicon wafer. The layer of photoresist may be tens to hundreds of microns thick. The photoresist-coated silicon wafer may be developed in UV light under a photomask in the design of the desired microfluidic features. The exposed photoresist may harden and the remaining unexposed photoresist may be dissolved off the silicon wafer. The resulting silicon “master” may exhibit protruding boss microstructures. Typically, more than one device design may be formed on a wafer. A layer of liquid silicone (e.g., polydimethylsiloxane silicone (“PDMS”)) may be poured over the silicon master and cured at high temperature. The silicone, which may be solid and rubbery after curing, may then be peeled away from the wafer, revealing embossed microfeatures. The individual device designs may be sliced from the silicon master with a craft blade. The embossed microstructures may be “capped” by sealing the silicone piece to either a microscope slide or another layer of silicone. Each silicon wafer may typically support a few hundred pours of PDMS before the photoresist microbosses begin to degrade.
Using PDMS is a common and straightforward means of hand-producing units in low volumes, but the resulting devices may have several drawbacks. Critically, PDMS may not be a viable candidate for mass production. Because the material properties of PDMS are quite distinct from those of the thermoplastics that are typically used in mass-production, results of experiments conducted with PDMS devices may not be representative of results achievable at scale. This may create problems as teams try to transition from phases of experimentation and prototyping to those of commercialization and volume.
Lamination is a process by which several layers of a device are cut independently and bonded together in a stack to form microfluidic features. A simple laminate may include an interface layer, a flow layer, and a sealing layer. The layers may be made from thermoplastics or glass and bonded using double-sided adhesive tape. In some examples, laser-cut adhesive tape may be used both as a flow layer and to bond the interface and sealing layers.
Lamination is an attractive method for making microfluidic devices because the materials are inexpensive, fabrication is quick and easy, and it is possible to use materials that provide optical access. However, the process may also have several drawbacks. Though adhesive tapes make bonding quick and easy, tapes may absorb chemicals and particles and may leak adhesive into the channels during use. In addition, devices that are bonded using adhesive tape generally cannot withstand high pressures and may be susceptible to bursting.
Micromachining is a means of subtractive manufacturing in which material is removed to form microfluidic features. This may be done by micro-milling or by laser etching. Though this process affords high accuracy and precision, resulting surface finishes may be uneven, impacting flow dynamics of downstream experiments. Additionally, production time is directly proportional to the number of devices made. At medium and high volumes, micromachining may not be cost-effective or time-effective.
Injection molding is a common method of mass-production for various devices. Molten plastic may be injected into mold cavities, where it cools and hardens to the shape of the cavity. Molds are generally made of machined and polished metal. In the case of microfluidic devices, which may require high-precision micromachining, molds may cost tens of thousands of dollars. Therefore, the high fixed cost of injection molding may only be economical at large order volumes.
Hot embossing is a thermal process where a stamp with raised features is pressed into a thermoplastic sheet heated slightly above its glass transition temperature. The glass transition temperature is a range of temperature in which a thermoplastic changes from a glassy state into a viscous state. As the stamp is pressed into the plastic, the plastic may slowly flow and the features of the stamp may be imprinted into its surface. The plastic and stamp may then be cooled to just below the glass transition temperature, where the plastic sheet hardens and returns to a glassy state. The tool and the plastic sheet may then be separated, yielding a rigid plastic sheet with imprinted microfluidic features. This method may reproduce microfluidic features with good fidelity.
In a typical hot embossing process, a blank thermoplastic sheet may be compressed between a fixed plate and a mold that contains an inverse of the geometry desired in the finished part. While the sheet is compressed, the temperature of the mold may be increased, and the thermoplastic sheet may take the shape of the mold.
Typically, the mold for this process is produced by photolithography, as described above. Alternatively, a mold can be produced by micro Computer Numerical Control (CNC) machining. However, both mold production techniques are prohibitively expensive and generally require weeks for production.
After an embossing, lamination, or micromachining process, devices must be sealed. This proves a difficult challenge in microfluidic device production as the manufacture must ensure the entire device is fluid tight, while also avoiding deforming or contaminating the microfeatures in the chip. Thermal diffusion bonding may meet these requirements. The thermal diffusion process works by heating a target sheet and a cover sheet of the same material to just below the glass transition temperature and applying a strong clamping force. The process may have similar requirements to hot embossing.
The following description includes a novel hot embossing process that addresses the shortcomings of the existing fabrication techniques described above. Using a 3D printed microfeature mold from a thermally stable photopolymer, the process disclosed herein may be faster and more cost-effective than the techniques described above.
In contrast to conventional molds used for hot embossing, the microfeature mold in the present disclosure may be formed from a thermally stable photopolymer using a 3D printing process. Suitable thermally stable photopolymers may include, for example, Accura® Bluestone™ distributed by 3D Systems Corporation or High Temp Resin distributed by Formlabs. The thermally stable photopolymer used to form the microfeature mold may have a heat deflection temperature that is able to withstand the high temperatures necessary in the hot embossing process. In an example, the heat deflection temperature may be higher than a glass transition temperature of a thermoplastic sheet used to form a device, as described below. For example, the thermally stable photopolymer used to form the microfeature mold may have a heat deflection temperature above 200° C.
Producing the microfeature mold via a 3D printing process may be more efficient than the conventional methods described above and may allow for the production of parts in less than a day as compared to weeks. Additionally, the flexible nature of the 3D printing process may provide many additional options for the design of the microfeature mold that may be helpful in the production process. For example, one or more core alignment features may be printed directly into one half of a microfeature mold. The one or more core alignment features may mate with one or more cavity alignment features that are printed directly into a second half of the microfeature mold. These features are described in detail below.
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The cavity tooling 122 may include one or more cavity alignment features 206, one or more fastener holes 806, and a recess 208. The core tooling 120 may contain one or more core alignment features 204, the one or more fastener holes 806, and a microfeature pattern 300 (shown below in
The one more fastener holes 806 may enable the core tooling 120 and the cavity tooling 122 to be attached to another component, such as a heating element, as described below. The one or more core alignment features 204 may mate with the one or more cavity alignment features 206 such that the core tooling 120 and the cavity tooling 122 are precisely aligned. The core tooling 120 may contain any number of core alignment features 204 and the cavity tooling 122 may include a corresponding number of cavity alignment features 204. It should be noted that
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To create the microfeature mold 113, the design of a proposed microfluidic chip must be defined. To create a chip with custom geometry, a three dimensional computer-aided-design (CAD) model may be created with a custom microfeature pattern 300 with specified widths, depths, and aspect ratios. The CAD model can be created via any one or more conventional software applications typically used in the art, such as Solidworks®, Pro/ENGINEER®, Onshape®, and CATIA®. The CAD model can be saved in any three dimensional filetype typically used in the art, such as .step, .iges, and .sldprt. Alternatively, designs for a microfluidic chip may be created via any two dimensional CAD program typically used in the art, such as Adobe Illustrator or Inkscape, and the depth of each microfeature may be specified.
A CAD model may be enlarged or shrunk by a necessary amount to account for the difference in thermal expansion between the microfeature mold and a target thermoplastic sheet to ensure microfeatures are reproduced accurately.
Upon successful design in CAD, a three dimensional model may be saved as a stereolithography interface format (.stl) file. Within the software used, adjustments may be made with regards to part orientation, resolution, and support. Once the desired properties for the part have been set, the file may be uploaded directly to the 3D printer. The build platform 701 may be lowered into the resin tank 809 such that there is a predetermined gap between a transparent window on a bottom of the resin tank 809 and the build platform 701. This may result in a thin layer of photopolymer resin remaining between the build platform 701 and the transparent window on the bottom of the resin tank 809. The optical curing source 808 may cure the thin layer of photopolymer resin to the build platform 701 in a pattern according to the design uploaded to the 3D printer. When the first layer is complete, the build platform 701 may be raised by a small increment, and the process may be repeated to form additional layers and build the one or more microfeatures.
The resolution of the 3D printer 810 may vary by its dimension. Features in the same plane as the build platform 701 (planar dimensions) may have higher resolution than features that are orthogonal to the build platform 701 (Z dimension). To optimize feature resolution, tooling may be printed in one of two orientations: flat against the build platform 701 or orthogonal to the build platform 701.
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In another example, components of the 3D printer 810 may be inverted and the build platform 701 may be located within the resin tank 809 and the optical curing source 808 may reside above the resin tank 809. The build platform 701 may be lowered deeper into the resin tank 809 incrementally. A new layer of photopolymer resin may flow in above the cured part, after which it may be cured by the optical curing source 808. This process may be repeated until the part is complete. In some instances, temporary support structures may be printed to stabilize geometry that would otherwise be too fragile or intricate to produce.
Depending on the photopolymer used, the completed part may require post-processing like additional curing in a light curing chamber, or thermal curing in an oven per manufacturer recommendations.
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The upper heating assembly 116 and the lower heating assembly 114 may each include an insulator 200 and a resistive heater 202. The resistive heater 202 may be composed of a soft silicone material and may have an internal resistive heating element. The soft silicone may provide compliance and may help maintain an even pressure across the microfeature mold 113 when it is compressed. When current is applied to the resistive heater 202, its surface temperature may increase rapidly and the insulator 200 may slow heat transfer to surrounding components.
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One or more apparatuses may be used to compress the microfeature mold 113 on the thermoplastic sheet 220. In general, any apparatus that is capable of providing compressive force to the thermoplastic sheet 220 through the microfeature mold 113 may be used. The following description includes a number of exemplary microfeature forming apparatuses.
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In an example, the cavity tooling 122 may be attached to the sliding plate 106. The core tooling 120 may be attached to the upper fixed plate 102. The compression apparatus 101 may use the hydraulic cylinder 110 to compress the sliding plate 106 against the upper fixed plate 102. The one or more guide rails 104 may be used to maintain the alignment of the sliding plate 106 relative to the upper fixed plate 102. The compression apparatus 101 may be used to create compressive forces in excess of 100 kilonewtons. The core tooling 120 and the cavity tooling 122 may be inverted so either is located on the upper or lower subassembly of the compression apparatus.
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In each of the microfeature forming systems described above, compression may be achieved with one or more of hydraulics, pneumatics, a rack-and-pinion assembly, mechanical linkages, screw-driven displacement, etc. The rate and scale of compression may be controlled via displacement measurement, force measurement, or a combination of both. In this configuration, the core tooling 120 and the cavity tooling 122 of the microfeature mold 113 may be inverted so either is fixed to the compression apparatus.
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The process described above may be faster, more versatile, and more repeatable than conventional processes used to form microfluidic devices. The microfeature forming system 100 may be easily adjustable for difference designs and since the 3D printing process is more precise than conventional methods, can create microfeatures with: small sizes, large sizes, varying Z-dimension, high or low aspect ratios, good optical clarity, and sharp internal corners. Resulting devices may be composed of thermoplastic materials and may have low auto-fluorescence, low gas permeability, and precise dimensions. In addition, the microfeature forming system 100 is self-aligning, representative of high-volume manufacturing, compatible with automation, and can be scaled so it is cost effective for a small to medium quantity of parts.
Although features and elements are described above in particular combinations, one of ordinary skill in the art will appreciate that each feature or element can be used alone or in any combination with the other features and elements.
This application claims priority to U.S. Provisional Application Ser. No. 63/004,014, filed Apr. 2, 2020, the content of which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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63004014 | Apr 2020 | US |