Microfluidic gravity pump with constant flow rate

• US 20030096405A1
• Filed: 07/18/2002
• Published: 05/22/2003
• Est. Priority Date: 07/18/2001
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Chang, Joseph, Takayama, Shuichi, Smith, Gary D., Cho, Brenda, Zhu, Xiaoyue, Huh, Dongeun
• Granted Patent: US 7,704,728 B2
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: F04B 19/006 Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/0357 For producing uniform flow
• CPC Class Codes: Y10T 137/4449 Gravity or capillary feed
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream

Abstract

A microfluidic system employs a microchannel and a gravity driven pump comprising horizontally oriented fluid supply reservoirs which supplies fluid to the microchannel at a substantially constant rate. The device is useful for numerous microfluidic applications, for example in the culture and/or treatment of biological systems under constant flow-induced stress, cell-size sorting, motile sperm sorting, or embryo culture.

Claims

1. A microfluidic device containing at least one gravity driven pump, comprising

a) at least one horizontally oriented fluid supply reservoir;

b) at least one microchannel, said microchannel in fluid communication with said fluid supply reservoir;

c) an outlet from said microchannel,

wherein said fluid supply reservoir is positioned above or is positionable above said outlet, and fluid in said supply reservoir exhibits gravity driven flow through said microchannel when said supply reservoir is positioned above said outlet.

2. The microfluidic device of claim 1, wherein said supply reservoir comprises a hollow length of tubing having an internal volume minimally 100 times the internal volume of said microchannel.

3. The microfluidic device of claim 2, wherein said supply reservoir has a circular, elliptical, or polyhedral internal cross-section.

4. The microfluidic device of claim 2, wherein said tubing is configured in a series of generally U-shaped bends or as a horizontal spiral.

5. The microfluidic device of claim 1, wherein said supply reservoir has an aspect ratio of at least 5:

1.

6. The microfluidic device of claim 1, wherein said reservoir has an internal diameter of such that fluid contained in said supply reservoir is confined within the supply reservoir when the reservoir is oriented horizontally but flows from the supply reservoir when connected to a liquid full microchannel and positioned above an outlet of said microchannel.

7. The microfluidic device of claim 1, wherein said supply reservoir has an internal dimension d and wherein said outlet of said microchannel is in fluid communication with an outlet reservoir having an internal dimension d′

such that capillary forces exerted between the supply liquid and the supply reservoir are substantially the same as the capillary forces exerted between the liquid and said outlet reservoir.

8. The microfluidic device of claim 1, wherein said microfluidic device has a flow rate of liquid through said microchannel, and said flow rate is constant within ±

1% of volume flow over a period of at least 24 hours when the height of said supply reservoir above said outlet is fixed.

9. The microfluidic device of claim 1, wherein the height of said supply reservoir above said outlet is alterable.

10. The microfluidic device of claim 1, comprising a single microchannel, said microchannel in fluid communication with minimally two horizontally oriented liquid supply reservoirs.

11. The microfluidic device of claim 1, comprising a plurality of microchannels, each microchannel in fluid communication with at least one horizontally oriented supply reservoir.

12. The microfluidic device of claim 11, wherein a plurality of microchannels are in fluid communication with one supply reservoir.

13. The microfluidic device of claim 1, wherein said microchannel comprises a polymer.

14. The microfluidic device of claim 1, wherein a microchannel of said microfluidic device comprises an organopolysiloxane polymer.

15. The microfluidic device of claim 1, wherein said microfluidic device is constructed such that at least said microchannel retains an open side onto which cells can be plated before producing a closed microchannel system.

16. The microfluidic device of claim 11, wherein selected portions of internal passages of said microfluidic device are treated with cell adhesive proteins and other selected portions are treated with a non-cell adhesive protein.

17. A microfluidic device of claim 1, said microfluidic device having a body portion, an inlet reservoir within said body portion in direct fluid communication with an upstream end of at least one microchannel, a secondary outlet reservoir in direct fluid communication with a downstream end of at least one microchannel, said inlet reservoir fluidly communicatable with a horizontally oriented liquid supply reservoir.

18. A method of biological cell culture wherein cultured cells are exposed to steady state stress associated with a constant flow of liquid, said method comprising plating cells within a microchannel of the microfluidic device of claim 1;

supplying cell growth media to said microchannel from at least one horizontally oriented supply reservoir; and

growing cells within said microchannel.

19. The method of claim 18, wherein cells grown within said microchannel are harvested from said outlet.

20. The method of claim 18, further comprising exposing said cells within said microchannel to at least one pharmacologically active substance, and monitoring the effect of said pharmacologically active substance on said cells under constant stress induced by fluid flow within said microchannel.

21. A method for embryo growth within a microchannel, said method comprising:

a) inserting an embryo into a microfluidic device of claim 1, a microchannel of said microfluidic device having an embryo retaining portion located within said microchannel; and

b) supplying said embryo with growth media from at least one fluid supply reservoir.

22. The method of claim 21 wherein said embryo retaining portion comprises a restriction or protuberance in said microchannel which restricts a clear path of said microchannel.