MICROFLUIDIC DEVICES AND METHODS OF MANUFACTURING
Microfluidic devices and associated methods of manufacturing are disclosed herein. In one embodiment, a method for method for producing a microfluidic device includes forming a target structural pattern on a substrate, the substrate having a polymeric substrate material with a solubility parameter. The method also includes selecting a bonding solvent based on a difference between the solubility parameter of the polymeric substrate material and a solubility parameter of the bonding solvent. The method further includes bonding the substrate having the target structural pattern with a cover using the selected bonding solvent.
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This application claims priority to U.S. Provisional Application No. 61/584,532, filed on Jan. 9, 2012.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCHThis work was supported in part by the National Science Foundation (CTS-0626471) and the National Institute of Health (NCRR1R21RR023146-01A2). The government has certain rights in this work.
BACKGROUNDThe field of microfluidics has recently drawn attention from many academic areas, such as sample concentration, continuous separation, chemical sensing, cell processing, genomics, metabolomics, and drug discovery. Microfluidics generally deals with behaviors, control, and manipulation of fluids that are geometrically constrained to a small scale (e.g., sub-millimeter).
However, affordable, reliable, and flexible microfluidic fabrication techniques are not readily available. Conventional techniques typically utilize glass and silicon because such materials may be readily processed using traditional microelectronics fabrication techniques. Glass and silicon also have high chemical resistance and well-characterized surface properties. However, drawbacks of such fabrication techniques include high cost, low throughput, device fragility, limitations on structure geometry, and poor sealing efficiencies. Polymers are promising alternatives to glass and silicon for being inexpensive, flexible in substrate selection, and easy to mass produce. For example, polydimethylsiloxane (PDMS) has been used in microfluidic fabrications with soft-lithography and oxygen plasma bonding techniques. However, PDMS channels delaminate at pressures above about 100 psi and are easily deformed at lower pressures.
Various embodiments of microfluidic devices and associated methods of manufacturing are described below. The term “microfluidic” is used throughout to refer to a feature having a hydraulic perimeter less than 1 millimeter. A person skilled in the relevant art will also understand that the technology may have additional embodiments, and that the technology may be practiced without several of the details of the embodiments described below with reference to
As discussed above, affordable, reliable, and flexible microfluidic fabrication techniques are not readily available. The inventor has recognized that bottlenecks in microfluidic fabrication include difficulties in imprinting a target pattern onto a polymeric substrate and securely bonding a microfluidic component with a protective cover. In response, several embodiments of the present technology provide an efficient and cost-effective method of forming a target pattern on a polymeric substrate.
Fabrication of polymeric microfluidic devices can include mold fabrication, replication of structures, and bonding. Metal wires, micro-machined silicon stamps, and metal molds have been used to imprint hard plastics. Silicon molds have also been used to transfer patterns by electroforming. These techniques, however, have their respective drawbacks. For example, silicon molds are fragile during hot embossing, and metal molds are expensive. As used herein, “hot-embossing” generally refers to a pattern imprinting process to transfer a pattern from a mold to a target material when the target material is softened by increasing temperature above a glass transition temperature of the target material.
In response, polymeric molds have been developed to imprint a desired pattern on a polymeric substrate. A polymeric mold typically includes a polymeric mold material attached to a backing material (e.g., glass or silicon). For example, a suitable mold material can include a negative photoresist with a highly cross-linked structure upon UV light exposure, high mechanical strength, good thermal stability and chemical resistance. However, due to incompatible thermal expansion and poor adhesion between the polymeric mold material and the backing material, such polymeric molds can only last a limited number of times during hot embossing.
In the discussion below, a list of materials is given for convenience and illustration. However a wide range of plastics, solvents and substrate materials, such as those listed in Table 1, may be used when performing the same steps to produce the same final result. As such, the list of materials presented herein is non-limiting and illustrative for the purposes of general explanation only. Additionally, while specific temperatures, pressures, solvents and lengths of time are described in the disclosure, the information below should be not be read as limiting to the applicability of additional pressures, temperatures, solvents and lengths of time for materials included in the broader disclosure but not discussed with similar specificity.
Plexiglas G-UVT PMMA was obtained from Arkema (Philadelphia, Pa.). This acrylic sheet can transmit over 80% ultraviolet (UV) light down to 285 nm in wavelength, without obvious UV transmission loss or yellowing after more than 7,000 hours of severe UVB weathering. SU-8 photoresist and developer were obtained from Microchem (Newton, Mass.). Glass plates (3×3″) were obtained from Sargent-Welch (Buffalo, N.Y.). Methylcellulose (400 cP viscosity of 2% aqueous solution at 25° C.), ethanolamine and barium hydroxide were purchased from Sigma (St. Louis, Mo.). Fluorescent proteins, r-phycoerythrin (PE) and green fluorescent protein (GFP) were obtained from Invitrogen (Eugene, Oreg.) and Millipore (Billerica, Mass.), respectively. PDMS (Sylgard 184) kit including base and curing agent were obtained from Dow Corning (Midland, Mich.). (3-trimethoxysilylpropyl)diethylenetriamine was obtained from Gelest inc. (Morrisville, Pa.). Tridecafluoro-1,1,2,2-tetradydrooctyl-trichlorosilane was from United Chemical Technologies Inc. (Bristol, Pa.). Hydrochloric acid was purchased from Fisher Scientific (Fair Lawn, N.J.). Concentrated sulfuric acid, 30% hydrogen peroxide and isopropanol (IPA) were obtained from Mallinckrodt Baker Inc. (Phillipsburg, N.J.).
As an initial operation of the process, a carrier substrate 100 may be prepared, as shown in
As shown in
As shown in
The process then includes forming a second polymeric mold (e.g., with a photoresist material and/or other suitable materials) based on the first polymeric mold. In the illustrated example, a sufficient amount of SU-8 2100 was poured into a plastic beaker and placed in a vacuum oven at 120° C. for 5 hours to remove its solvent. After solvent evaporation, the oven was vented to atmospheric pressure to form a SU-8 melt. The PDMS mold was put into the oven. SU-8 melt was cast on the PDMS mold and allowed to cool down to room temperature in the oven. As shown in
As shown in
The process may then include drilling holes (not shown) at suitable positions relative to channels 112 on the embossed PMMA plate. The process may then include attaching a cover 114 to the embossed polymeric substrate 110, as shown in
The bonding system was disassembled to release the bonded PMMA plates (referred herein as a “chip”). In certain embodiments, the process can optionally include removing residual solvent to restore transparency and/or annealing to attenuate internal stresses that resulted from bonding. For example, in the illustrated example, the chip was put in a 70° C. oven for one hour to evaporate IPA and then in a 100° C. oven for another hour. In other embodiments, the foregoing operations may be omitted.
Even though an SU-8 mold was formed as an example of the second polymeric mold 106, in other embodiments, the second polymeric mold 106 can also include a hybrid mold (e.g., constructed from both an epoxy and a glass). For example, in in one instance, the PDMS mold may be peeled off from the SU-8/glass hybrid mold. The PDMS mold may be placed on a center of a cover plate to enclose the channel. A low-viscosity adhesive may be used to fill the channel between the PDMS mold and the cover plate. The adhesive-filled assembly is placed in an oven for 4 hours at 120° C. followed by 2 hours at 175° C. After the adhesive is hardened, the PDMS mold is peeled off and may be used again. The epoxy/glass hybrid mold may be used to emboss the polymeric substrate 110, as shown in
Referring back to
Without being bound by theory, for dissolution of a polymer into a solvent, the process is thermodynamically determined by a free energy change of mixing as follows:
ΔG=ΔH−TΔS
where ΔG is a change in Gibbs free energy, ΔH is a change in enthalpy, T is an absolute temperature, and ΔS is a change in entropy on mixing. When the free energy change is negative, the dissolving process is believed to be thermodynamically favorable. Solubility parameters or Hildebrand parameters, δ, describe the enthalpy change of simple liquids and polymers. For a binary regular solution, the enthalpy change is given as
ΔH=(δ1−δ2)2φ1φ2V
where δ1 and φ1 are a solubility parameter and a volume fraction of component 1, respectively, δ2 and φ2 are a solubility parameter and a volume fraction of component 2, respectively, and Vis the volume of the mixture.
The solubility parameters provide a measure of molecular attraction of a substance and may be used to predict solubility of a polymer in a solvent. It is believed that, in certain embodiments, two components are soluble if their solubility parameters differ by less than about 1.0 (cal/cm3)0.5. Therefore, suitable solvents for PMMA (9.3 (cal/cm3)0.5) can include toluene (8.9 (cal/cm3)0.5), benzene (9.2 (cal/cm3)0.5), chloroform (9.3 (cal/cm3)0.5), tetrahydrofuran (THF, 9.3 (cal/cm3)0.5), methyl chloride (9.7 (cal/cm3)0.5), ethylene dichloride (9.8 (cal/cm3)0.5), and isopropanol (IPA, δ=11.5 (cal/cm3)0.5). Other example solvents for various polymeric materials are listed in the table below. In other embodiments, the solvent may be selected to have their solubility parameters differ by less than about 0.9 (cal/cm3)0.5, about 0.7 (cal/cm3)0.5, about 0.5 (cal/cm3)0.5, and/or other suitable values.
As a result, the bonding solvent may be selected to have a target difference in solubility parameters such that dissolution of the polymeric substrate 110 occurs only at a thin layer (e.g., 10 microns) on the surface. Once a bonding solvent is chosen, the process also includes controlling a bonding temperature based on the free energy change of solution. As a result, strong bonding may be achieved without damage to integrity of the channels 112 and without using a sacrificial material in the channels 112. Even though the cover 114 is discussed above with reference to
From the foregoing, it will be appreciated that specific embodiments of the disclosure have been described herein for purposes of illustration, but that various modifications may be made without deviating from the disclosure. For example, instead of using PMMA as the polymeric substrate, polycarbonate (PC), cyclic olefin copolymers (COC), polystyrene (PS), and/or other suitable polymeric materials may also be used. In addition, many of the elements of one embodiment may be combined with other embodiments in addition to or in lieu of the elements of the other embodiments. Accordingly, the technology is not limited except as by the appended claims.
Claims
1. A method for producing a microfluidic device, comprising:
- depositing a photoresist material onto a carrier substrate;
- patterning the deposited photoresist material to have a target pattern on the carrier substrate;
- transferring the target pattern from the carrier substrate to a first mold of a first polymeric material;
- forming a second mold of a second polymeric material with the first polymeric mold, the second mold having a mold pattern corresponding to the target pattern, wherein the second polymeric material is different than the first polymeric material; and
- imprinting a substrate with the mold pattern using the second mold, the substrate having a polymeric substrate material.
2. The method of claim 1 further comprising bonding the imprinted substrate with a cover using a solvent, the cover having the same polymeric substrate material.
3. The method of claim 2, further comprising removing residual solvent to increase transparency after bonding the imprinted substrate with the cover.
4. The method of claim 1 wherein the polymeric substrate material includes poly(methyl methacrylate), and the method further includes bonding the imprinted substrate with a cover using a solvent selected from the group consisting of isopropanol, n-butanol, and cyclohexanol.
5. The method of claim 1 wherein the polymeric substrate material includes polystyrene, and the method further includes bonding the imprinted substrate with a cover using a solvent selected from the group consisting of isopropanol, n-butanol, cyclohexanol.
6. The method of claim 1 wherein the polymeric substrate material includes polycarbonate, and the method further includes bonding the imprinted substrate with a cover using a solvent selected from the group consisting of dimethylformamide, ethanol, diethyl ether, n-heptane.
7. The method of claim 1 wherein the polymeric substrate material includes cyclo-olefin copolymer, and the method further includes bonding the imprinted substrate with a cover using a solvent selected from the group consisting of cyclohexane, ethylactate, diacetone alcohol, 1,2 dichloropropane, carbon tetrachloride, xylene, and toluene.
8. A method for method for producing a microfluidic device, comprising:
- forming a target structural pattern on a substrate, the substrate having a polymeric substrate material with a solubility parameter;
- selecting a bonding solvent based on a difference between the solubility parameter of the polymeric substrate material and a solubility parameter of the bonding solvent; and
- bonding the substrate having the target structural pattern with a cover using the selected bonding solvent.
9. The method of claim 8 wherein selecting the bonding solvent includes:
- determining a difference between the solubility parameter of the polymeric substrate material and a solubility parameter of a candidate solvent; and
- if the determined difference is less than about 1.0 (cal/cm3)0.5, selecting the candidate solvent as the bonding solvent.
10. The method of claim 8 wherein selecting the bonding solvent includes:
- determining a difference between the solubility parameter of the polymeric substrate material and a solubility parameter of a candidate solvent; and
- based on the determined difference, predicting solubility of the polymeric substrate material in the candidate solvent.
11. The method of claim 8 wherein selecting the bonding solvent includes: where δ1 and φ1 are a solubility parameter and a volume fraction of component 1, respectively, δ2 and φ2 are a solubility parameter and a volume fraction of component 2, respectively, and V is a mixture volume of the candidate solvent and the polymeric substrate material; and where ΔG is a change in Gibbs free energy, ΔH is a change in enthalpy, T is an absolute temperature, and ΔS is a change in entropy on mixing; and
- calculating an enthalpy change as follows: ΔH=(δ1−δ2)2φ1φ2V
- calculating a free energy change of mixing as follows: ΔG=ΔH−TΔS
- predicting solubility of the polymeric substrate material in the candidate solvent based on the calculated free energy change.
12. The method of claim 8 wherein bonding the substrate includes bonding the substrate having the target structural pattern with the cover using the selected bonding solvent without protecting the target structural pattern with a sacrificial material.
13. The method of claim 8 wherein bonding the substrate includes:
- bonding the substrate having the target structural pattern with the cover using the selected bonding solvent without protecting the target structural pattern with a sacrificial material; and
- fastening the cover to the substrate with the formed bond generally without damage to the target structural pattern on the substrate.
14. The method of claim 8 wherein:
- the polymeric substrate material includes poly(methyl methacrylate) having a solubility parameter of about 9.3 (cal/cm3)0.5; and
- selecting the bonding solvent includes selecting a solvent with a solubility parameter greater than about 8.3 (cal/cm3)0.5 and lower than about 11.6 (cal/cm3)0.5.
15. The method of claim 8 wherein bonding the substrate includes bonding the substrate having the target structural pattern with a cover using the selected bonding solvent, the cover having the same polymeric substrate material as the substrate.
16. A method for method for producing a microfluidic device, comprising:
- forming a target structural pattern on a substrate, the substrate having a polymeric substrate material;
- bonding the substrate having the target structural pattern with a cover using a bonding solvent at a bonding temperature, wherein a difference in solubility parameter between the polymeric substrate material and the bonding solvent is lower than about 1.0 (cal/cm3)0.5; and
- controlling the bonding temperature based on a free energy change corresponding to the polymeric substrate material dissolving in the bonding solvent.
17. The method of claim 16 wherein controlling the bonding temperature includes: where δ1 and φ1 are a solubility parameter and a volume fraction of component 1, respectively, δ2 and φ2 are a solubility parameter and a volume fraction of component 2, respectively, and V is a mixture volume of the candidate solvent and the polymeric substrate material; where ΔG is a change in Gibbs free energy, ΔH is a change in enthalpy, T is an absolute temperature, and ΔS is a change in entropy on mixing; and
- calculating an enthalpy change as follows: ΔH=(δ1−δ2)2φ1φ2V
- with the calculated enthalpy change, calculating a free energy change of mixing as follows: ΔG=ΔH−TΔS
- controlling the bonding temperature based on the calculated Gibbs free energy.
18. The method of claim 16 wherein controlling the bonding temperature includes selecting a bonding temperature such that the target structural pattern on the substrate is generally not damaged during bonding.
19. The method of claim 16 wherein bonding the substrate includes bonding the substrate with the cover without using a sacrificial material on the substrate, and wherein controlling the bonding temperature includes selecting a bonding temperature such that the target structural pattern on the substrate is generally not damaged during bonding.
20. The method of claim 16 wherein controlling the bonding temperature includes controlling the bonding temperature based at least in part on the difference in solubility parameter between the polymeric substrate material and the bonding solvent.
Type: Application
Filed: Feb 10, 2012
Publication Date: Jul 11, 2013
Applicant: WASHINGTON STATE UNIVERSITY RESEARCH FOUNDATION (Pullman, WA)
Inventor: Cornelius F. Ivory (Pullman, WA)
Application Number: 13/371,265
International Classification: C09J 5/00 (20060101); B29C 33/38 (20060101);