Microfermentor device and cell based screening method

• US 20030077817A1
• Filed: 04/10/2002
• Published: 04/24/2003
• Est. Priority Date: 04/10/2001
• Status: Abandoned Application

• Current Assignee: BioProcessors Corp.
• Original Assignee: BioProcessors Corp.
• Inventors: Fama, Lawrence, Schreyer, H. Brett, Heibel, Anne, Zarur, Andrey J.
• Application Number:
  US10/119,917
• Publication Number:
  US 20030077817A1
• Time in Patent Office: Days
• US Class Current: 435/305.2
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 41/12 of temperature controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00
• CPC Class Codes: C12M 41/26 of pH
• CPC Class Codes: C12M 41/32 of substances in solution
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: C12M 41/40 of pressure

Abstract

A microfermentor device that can be used for a wide variety of purposes is described. The microfermentor device includes one or more cell growth chambers having a volume of less than 1 ml. The microfermentor device can be used to grow cells used for the production of useful compounds, e.g., therapeutic proteins, antibodies or small molecule drugs. The microfermentor device can also be used in various high-throughput screening assays. For example, the microfermentor device can be used to screen compounds to assess their effect on cell growth and/or a normal or abnormal biological function of a cell and/or their effect on the expression of a protein expressed by the cell. The device can also be used to investigate the effect of various environmental factors on cell growth, biological function or production of a cell product. The device, including various controlling components and sensing components can be microfabricated on a support material.

Claims

1. A microfermentor device comprising:

a substrate having at least one surface;

a cell culture chamber having a volume of less than about 1000 μ

l fabricated into the surface of the substrate;

at least a first and a second channel fabricated into the surface of the substrate and fluidly connected to the chamber; and

an optical sensor in optical communication with the chamber.

2. The device of claim 1 wherein the chamber has a volume of less than 100 μ

l.

3. The device of claim 1 wherein the chamber has a volume of less than 10 μ

l.

4. The device of claim 1 wherein the chamber has a volume of less than 1 μ

l.

5. The device of claim 1 wherein the first channel is fluidly connected to a mixing chamber.

6. The device of claim 5 wherein the mixing chamber is fluidly connected to a plurality of inlet channels.

7. The device of claim 6 wherein the mixing chamber and the plurality of inlet channels are fabricated in the surface of the substrate,

8. The device of claim 1 wherein the substrate is formed of a material selected from the group consisting of glass, silicon, metal, and a polymer.

9. The device of claim 1 wherein the chamber is lined with a material to which mammalian cells adhere.

10. The device of claim 1 wherein the chamber contains a matrix material to which cells adhere.

11. The device of claim 1 further comprising a sensor for monitoring the temperature within the chamber.

12. The device of claim 1 further comprising a sensor for monitoring the pH within the chamber.

13. The device of claim 1 further comprising a sensor for monitoring the pressure within the chamber.

14. The device of claim 1 further comprising a sensor for monitoring the optical density within the chamber.

15. The device of claim 1 further comprising a sensor for monitoring the glucose concentration within the chamber.

16. The device of claim 1 comprising at least 10 chambers.

17. The device of claim 16 comprising at least 20 chambers.

18. The device of claim 17 comprising at least 50 chambers.

19. The device of claim 18 comprising at least 100 chambers.

20. A method for screening a plurality of test compounds, the method comprising:

providing substrate having a surface into which is fabricated a plurality of cell culture chambers having a volume less than about 1000 μ

l and containing cells, each of the cell culture chambers being fluidly connected to at least a first and a second microchannel fabricated into the surface of the substrate;

culture chambers being fluidly connected to at least a first and a second microchannel fabricated into the surface of the substrate;

introducing each of the plurality of test compounds into at least one of the plurality of cell culture chambers; and

monitoring the effect of each of the plurality of test compounds on a biological response of the cells.

21. The method of claim 20 wherein the biological response is cell growth.

22. The method of claim 20 wherein the biological response is production by the cells of a selected molecule.

23. The method of claim 20 wherein the biological response is uptake by the cells of a selected molecule.

24. The method of claim 20 wherein the step of monitoring comprises measuring a fluorescent signal that is influenced by the biological response.

25. The method of claim 20 wherein the device comprises at least a first and a second cell culture chamber, the first cell chamber containing a first type of cell and the second cell culture chamber containing a second type of cell.