Devices and methods for pharmacokinetic-based cell culture system

• US 7,288,405 B2
• Filed: 04/25/2002
• Issued: 10/30/2007
• Est. Priority Date: 04/25/2001
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Shuler, Michael, Meyers, Scott, Baxter, Gregory T., Sin, Aaron, Harrison, Robert Andrew
• Primary Examiner(s): Beisner; William H.
• Application Number:
  US10/133,977
• Publication Number:
  US 20030082795A1
• Time in Patent Office: 2,014 Days
• Field of Search: 435/373, 435/293.1, 435/294.1, 435/305.3, 435/292.1
• US Class Current: 435/288.5
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 23/44 Multiple separable units; Modules
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0671 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5067 Liver cells

Abstract

Devices, in vitro cell cultures, systems, and methods are provided for microscale cell culture analogous (CCA) device.

Claims

1. A pharmacokinetic based microscale culture device, comprising:

a first microscale chamber containing a first type of cell, wherein the first microscale chamber is dimensioned to maintain the first type of cell under conditions that give rise to at least one pharmacokinetic parameter value comparable to a value for the same at least one pharmacokinetic parameter obtained with respect to the same type of cell in vivo, wherein the at least one pharmacokinetic parameter value is selected from the group consisting of a measurement of liquid residence time, and liquid to cell ratio, wherein the first chamber comprises a first inlet and a first outlet for flow of culture medium;

a second microscale chamber containing a second type of cell, wherein the second microscale chamber is dimensioned to maintain the second type of cell under conditions that give rise to at least one pharmacokinetic parameter value comparable to a value for the same at least one pharmacokinetic parameter obtained with respect to the same type of cell in vivo, wherein the second chamber comprises a second inlet and a second outlet for flow of culture medium; and

a microfluidic channel interconnecting the first and second microscale chambers wherein the microfluidic channel is dimensioned to transport a culture medium, and wherein the microscale culture device is dimensioned to maintain at least one desired value for shear stress under a condition of flow of the culture medium.

2. The culture device of claim 1, further comprising one or more additional microscale chambers dimensioned to maintain an additional type of cell under conditions that give rise to at least one pharmacokinetic parameter value comparable to a value for the same at least one pharmacokinetic parameter obtained with respect to the same type of cell in vivo, wherein the one or more additional chambers comprise an inlet and outlet for flow of culture medium.

3. The culture device of claim 1, further comprising culture medium.

4. The culture device of claim 3, wherein the culture medium flows through the chambers.

5. The culture device of claim 3, wherein the culture medium flows re-circulated through the chambers.

6. The culture device of claim 1, further comprising a pumping mechanism.

7. The culture device of claim 6, wherein the pumping mechanism is integrated in the device.

8. The culture device of claim 6, wherein the pumping mechanism is external to the device.

9. The culture device of claim 1, further comprising a debubbler located within the microfluidic channel.

10. The culture device of claim 1, further comprising a debubbler located externally to the device.

11. The culture device of claim 1, further comprising at least one sensor for obtaining signals from cultured cells.

12. The culture device of claim 11, wherein the at least one sensor is a biosensor.

13. The culture device of claim 11, wherein the at least one sensor comprises a waveguide.

14. The culture device of claim 1, wherein the device is microfabricated.

15. The culture device of claim 1, wherein the device is manufactured from a microfabricated master.

16. The culture device of claim 1, wherein at least one of the chambers provides for three dimensional growth of cells.

17. The culture device of claim 1, wherein at least one of the chambers contains a plurality of cells.

18. The culture device of claim 1, wherein at least one of the chambers contains a tissue biopsy.

19. The culture device of claim 1, wherein at least one of the chambers contains a cross section of a tissue.

20. The culture device of claim 18 or 19, wherein the tissue is healthy or diseased.

21. The culture device of claim 18 or 19, wherein the tissue is an artery, vein, gastrointestinal tract, esophagus, or colon.

22. The culture device of claim 1, wherein at least one of the chambers contains a cross section of an organ.

23. The culture device of claim 22, wherein the organ is healthy or diseased.

24. The culture device of claim 22, wherein the organ is a heart, brain, kidney, lung, or muscle.

25. The culture device of claim 1, wherein at least one of the chambers contains circulating or adherent cells.

26. The culture device of claim 1, wherein at least one of the chambers contains eukaryotic cells.

27. The culture device of claim 26, wherein the eukaryotic cells are plant or animal cells.

28. The culture device of claim 27, wherein the cells are mammalian cells.

29. The culture device of claim 1, wherein at least one of the chambers contains prokaryotic cells.

30. The culture device of claim 1, wherein the cells are primary cells.

31. The culture device of claim 1, wherein the cells are tumor cells.

32. The culture device of claim 1, wherein the cells are stem cells.

33. The culture device of claim 1, wherein the cells are genetically altered, transformed or immortalized cells.