Microfluidic Structures for Biomedical Applications

• US 20090181200A1
• Filed: 09/19/2008
• Published: 07/16/2009
• Est. Priority Date: 09/19/2007
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Charles Stark Draper Laboratory Incorporated, Massachusetts Institute of Technology
• Original Assignee: Charles Stark Draper Laboratory Incorporated
• Inventors: Khalil, Ahmad S., Mack, Peter, Tupper, Malinda M., Hsiao, James C., Borenstein, Jeffrey T., Tao, Sarah L., Garcia-Cardena, Guillermo, Weinberg, Eli J.
• Granted Patent: US 8,266,791 B2
• Time in Patent Office: Days
• US Class Current: 428/36.900
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B29C 33/3857 by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts
• CPC Class Codes: B29C 59/02 by mechanical means, e.g. pressing B29C59/007 takes precedence; embossing expanded porous articles B29C44/5627
• CPC Class Codes: B29K 2025/06 PS, i.e. polystyrene
• CPC Class Codes: B29L 2031/753 Medical equipment; Accessories therefor bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81B 2203/0338 Channels
• CPC Class Codes: B81B 2203/0376 rounded profile
• CPC Class Codes: B81C 1/00119 Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: B81C 99/0085 using moulds and master templates, e.g. for hot-embossing
• CPC Class Codes: Y10T 156/1039 Surface deformation only of sandwich or lamina [e.g., embossed panels]
• CPC Class Codes: Y10T 29/49126 Assembling bases
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base
• CPC Class Codes: Y10T 29/49156 with selective destruction of conductive paths
• CPC Class Codes: Y10T 29/49401 Fluid pattern dispersing device making, e.g., ink jet
• CPC Class Codes: Y10T 428/139 Open-ended, self-supporting conduit, cylinder, or tube-type article

Abstract

Microfluidic structures featuring substantially circular channels may be fabricated by embossing polymer sheets.

Claims

1. A method for fabricating a microfluidic structure, comprising:

(a) providing a patterned wafer comprising at least one exposed electrically conductive region and at least one exposed electrically insulating region;

(b) electroplating an inverse channel portion with substantially semicircular cross section onto the wafer, thereby forming a first master mold;

(c) employing the first master mold so as to emboss a channel portion in a first polymer sheet;

(d) aligning and bonding the first polymer sheet with a second polymer sheet having a corresponding channel portion such as to define a first channel with substantially circular cross section between the polymer sheets.

2. The method of claim 1 further comprising employing the first master mold so as to emboss a channel portion in the second polymer sheet.

3. The method of claim 1 further comprising repeating steps (a) and (b) to form a second master mold having an inverse channel portion substantially mirror symmetric to the channel portion on the first master mold, and employing the second master mold so as to emboss a channel portion in the second polymer sheet.

4. The method of claim 1 wherein step (c) comprises directly embossing the master mold into the first polymer sheet.

5. The method of claim 1 wherein step (c) comprises embossing the master mold into a first transfer mold, embossing the first transfer mold into a second transfer mold, and embossing the second transfer mold into the first polymer sheet.

6. The method of claim 1 wherein, for any first diameter of the channel and any second diameter of the channel intersecting with the first diameter, the ratio of the first diameter to the second diameter is less than 1.3.

7. The method of claim 1 wherein the channel is characterized by a gradually changing diameter.

8. The method of claim 1 wherein the first channel bifurcates into at least a second channel and a third channel, a first passage between the first channel and the second channel and a second passage between the first channel and the third channel being smooth and gradual.

9. The method of claim 1 wherein the electrically conductive region comprises a metal selected from the group consisting of chromium, gold, titanium, tungsten, platinum, silver, aluminum, and copper.

10. The method of claim 1 wherein the electrically insulating region comprises a material selected from the group consisting of silicon dioxide and silicon nitride.

11. The method of claim 1 wherein the patterned wafer further comprises a substrate, and wherein the electrically conductive region is deposited on the substrate, and the electrically insulating region is deposited on the electrically conductive region.

12. The method of claim 11 wherein the substrate comprises silicon.

13. The method of claim 11 wherein the electrically conductive region is continuous.

14. The method of claim 11 wherein the electrically conductive region is discontinuous.

15. The method of claim 1 wherein the patterned wafer further comprises a substrate, and wherein the electrically insulating region is deposited on the substrate, and the electrically conductive region is deposited on the electrically insulating region.

16. The method of claim 1 wherein the electroplated inverse channel portion comprises a metal selected from the group consisting of copper, nickel, silver, and gold.

17. The method of claim 1 further comprising:

(e) optionally repeating steps (a) and (b), and repeating steps (c) and (d) to form a plurality of microfluidic structures;

(f) stacking the plurality of microfluidic structures to form a stacked microfluidic structure that defines a front surface comprising outlets of the channels;

(g) repeating steps (a), (b), (c), and (d) to form a microfluidic header; and

(h) coupling the microfluidic header to the front surface defined by the stacked microfluidic structure, and aligning the microfluidic header to the outlets of the channels so as to fluidically couple the microfluidic structures together.

18. The method of claim 1 further comprising seeding cells within the channel.

19. A microfluidic structure, comprising:

a polymer scaffold defining a first channel therein, at least a portion of the first channel being characterized by a substantially circular cross section and a diameter less than 300 micrometers.

20. The microfluidic structure of claim 19 wherein, for any first diameter of the channel and any second diameter of the channel intersecting with the first diameter, the ratio of the first diameter and the second diameter is less than 1.3.

21. The microfluidic structure of claim 19 wherein, for any first diameter of the channel and any second diameter of the channel intersecting with the first diameter, the ratio of the first diameter and the second diameter is less than 1.1.

22. The microfluidic structure of claim 19 wherein the first channel is further characterized by a gradually changing diameter.

23. The microfluidic structure of claim 19 wherein the first channel bifurcates into at least a second channel and a third channel, a first passage between the first channel and the second channel and a second passage between the first channel and the third channel being smooth and gradual.

24. The microfluidic structure of claim 19 further comprising cells seeded within the first channel.

25. A microfluidic device, comprising:

(a) a plurality of microfluidic structures, each structure comprising a polymer scaffold defining at least one channel therein, the plurality of microfluidic structures being stacked so as to form a stacked microfluidic structure that defines a front surface comprising outlets of the channels; and

(b) a microfluidic header comprising at least one polymer scaffold that defines a network of channels therein, the microfluidic header being coupled to the front surface of the stacked microfluidic structure and aligned with the outlets of the channels so as to fluidically couple the microfluidic structures together.

26. The microfluidic device of claim 25 wherein the microfluidic header comprises a plurality of polymer scaffolds, each polymer scaffold defining a network of channels therein.

27. The microfluidic device of claim 25 further comprising cells seeded within the channels.

28. The microfluidic device of claim 25 wherein at least a portion of at least one channel is characterized by a substantially circular cross section and a diameter less than 300 micrometers.

29. A method for fabricating a microfluidic structure, comprising:

(a) providing a patterned wafer;

(b) isotropically etching the wafer with xenon difluoride so as to form a master mold defining an inverse channel portion with substantially semicircular cross section;

(c) embossing the master mold into a transfer mold;

(d) embossing the transfer mold into a first polymer sheet; and

(e) aligning and bonding the first polymer sheet and a second polymer sheet having a corresponding channel portion such as to define a first channel with substantially circular cross section between the polymer sheets.

30. The method of claim 29 wherein a diameter of the inverse channel portion changes gradually from a first diameter to a second diameter.