DEVICES AND METHODS FOR PHARMACOKINETIC-BASED CELL CULTURE SYSTEMS

• US 20070026519A1
• Filed: 09/08/2006
• Published: 02/01/2007
• Est. Priority Date: 04/25/2001
• Status: Abandoned Application

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Harrison, Robert, Shuler, Michael, Meyers, Scott, Sin, Aaron, Baxter, Gregory
• Application Number:
  US11/530,390
• Publication Number:
  US 20070026519A1
• Time in Patent Office: Days
• US Class Current: 435/325
• 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 dimensioned to maintain biological material under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter obtained in vivo, wherein the first microscale chamber comprises a first inlet and a first outlet for flow of fluid;

a second microscale chamber dimensioned to maintain biological material under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter obtained in vivo, wherein the second microscale chamber comprises a second inlet and a second outlet for flow of fluid;

a microfluidic channel interconnecting the first and second microscale chambers wherein the microfluidic channel is dimensioned to transport the fluid; and

a substance that is configured to adhere a portion of the biological material to a portion of the first or second microscale chambers or to a portion of the microfluidic channel.

8. The device of claim 1 further comprising at least one microfluidic channel connected to the microscale feature.

9. The device of claim 8 wherein the substance is located within a portion of the microfluidic channel.

2. A device comprising:

at least one microscale feature dimensioned to maintain biological material under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter found in vivo; and

a substance that is configured to adhere, segregate, or immobilize a portion of the biological material to or within a portion of the device.

3. The device of claim 2 wherein the substance is a material or structure.

4. The device of claim 2 wherein a portion of the device is coated with the substance.

5. The device of claim 2 wherein a portion of the microscale feature is coated with the substance.

6. The device of claim 2 wherein the substance is selected from least one of the group consisting of a protein, collagen, MATRIGEL, a hydrogel, a scaffold, and a matrix, a construct consisting of multiple layers of collagen separated by biological material, a construct consisting of multiple layers separated by biological material, wherein one or both layers are comprised of materials selected from at least one of the group consisting of a protein, collagen, MATRIGEL, and a matrix.

7. The device of claim 2 wherein the substance is incubated.

10. The device of claim 2 wherein the substance is applied to, formed in, contained in, assembled in, made in, constituted in or inserted into the device or the microscale feature.

11. The device of claim 2 wherein the adherence, segregation, or immobilization of the biological material provides the at least one pharmacokinetic parameter.

12. The device of claim 2 wherein the adherence, segregation or immobilization of the biological material enables the provision of at least one pharmacokinetic parameter.

13. The device of claim 2 wherein the geometry of the microscale feature or the device in whole or in part is based on a mathematical model or wherein the geometry of interconnection of one or more microscale features or the device in whole or in part is based on a mathematical model.

14. The device of claim 13 wherein the mathematical model is a physiologically-based pharmacokinetic (“

PBPK”

) model.

15. The device of claim 2 wherein the microscale feature is selected from at least one of the group consisting of a chamber, a channel, a tube, a well, a scaffold, an inlet, an outlet, a valve, a membrane, a diaphragm, or a compartment.

16. The device of claim 2 wherein the biological material is selected from at least one of the group consisting of healthy tissue, diseased tissue, a portion of a tissue biopsy, a portion of tissue, a portion of an artery, a portion of a vein, a portion of a gastrointestinal tract, a portion of an esophagus, a portion of a colon, a portion of an organ, a portion of a heart, a portion of a brain, a portion of a kidney, a portion of a lung, a portion of a muscle, a cell culture, an eukaryotic cell, a plant cell, an animal cell, a mammalian cell, a prokaryotic cell, a primary cell, a tumor cell, a stem cell, a genetically altered cell, a transformed cell, and an immortalized cell.

17. The device of claim 2 wherein the microscale feature further contains circulating, immobilized, or adherent biological material.

18. The device of claim 2 wherein the at least one pharmacokinetic parameter is selected from at least one of the group consisting of tissue size ratio, tissue to blood volume ratio, drug residence time, measurement of interactions between cells, liquid residence time, liquid to cell ratios, metabolism by cells, shear stress, flow rate, geometry, the number of cells in the culture device, circulatory transit time, and liquid distribution.

19. A method of culturing biological material comprising:

maintaining biological material with a first microscale chamber under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter obtained in vivo, wherein the first microscale chamber comprises a first inlet and a first outlet for flow of fluid;

maintaining biological material with a second microscale chamber under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter obtained in vivo, wherein the second microscale chamber comprises a second inlet and a second outlet for flow of fluid;

interconnecting the first and second microscale chambers with a microfluidic channel wherein the microfluidic channel is dimensioned to transport the fluid; and

adhering a portion of the biological material to a portion of the first or second microscale chambers or to a portion of the microfluidic channel.

20. A method comprising:

maintaining biological material with at least one microscale feature under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter found in vivo; and

adhering, segregating, or immobilizing a portion of the biological material to or within a portion of a device, which device contains the microscale feature.

21. The method of claim 20 further comprising coating a portion of the device with a substance that adheres, segregates, or immobilizes a portion of the biological material to or within the portion of the device.

22. The method of claim 20 further comprising coating a portion of the microscale feature with a substance that adheres, segregates or immobilizes a portion of the biological material to or within the portion of the microscale feature.

23. The method of claim 20 wherein the adhering, segregating or immobilizing comprises applying, making, assembling, forming, inserting or constituting a substance that adheres, segregates or immobilizes the biological material to or within a portion of the device.

24. The method of claim 23 wherein the substance is selected from at least one of the group consisting of a protein, collagen, MATRIGEL, a hydrogel, a scaffold, a construct consisting of multiple layers of collagen separated by biological material, a construct consisting of multiple layers separated by biological material, wherein one or both layers are comprised of materials selected from at least one of the group consisting of a protein, collagen, MATRIGEL, and a matrix.

25. The method of claim 20 wherein the adhering, segregating, or immobilizing comprises incubating a substance within the device.

26. The method of claim 20 further comprising at least one microfluidic channel connected to the microscale feature.

27. The method of claim 26 further comprising locating the substance within a portion of the microfluidic channel.

28. The method of claim 20 further comprising applying, forming, containing, inserting, assembling, making or constituting the substance to, in, or into the device or the microscale feature.

29. The method of claim 20 wherein the adhering, segregating, or immobilizing of the portion of the biological material enables the provision of the at least one pharmacokinetic parameter.

30. The method of claim 20 wherein the microscale feature is selected from at least one of the group consisting of a chamber, a channel, a tube, a well, a scaffold, an inlet, an outlet, a valve, a membrane, a diaphragm, or a compartment.

31. The method of claim 20 wherein the at least one pharmacokinetic parameter is selected from at least one of the group consisting of tissue size ratio, tissue to blood volume ratio, drug residence time, measurement of interactions between cells, liquid residence time, liquid to cell ratios, metabolism by cells, shear stress, flow rate, geometry, the number of cells in the culture device, circulatory transit time, and liquid distribution.

32. A method comprising:

forming a microscale feature that is dimensioned to maintain biological material under conditions that provide a value of at least one pharmacokinetic parameter in vitro that is comparable to a value of at least one pharmacokinetic parameter found in vivo; and

adding a substance to adhere, segregate, or immobilize a portion of the biological material to or within a portion of a device that contains the microscale feature.

33. The method of claim 32 further comprising coating a portion of the device with the substance.

34. The method of claim 32 further comprising coating a portion of the microscale feature with the substance.

35. The method of claim 32 wherein the substance is selected from least one of the group consisting of a protein, collagen, MATRIGEL, a hydrogel, a scaffold, a construct consisting of multiple layers of collagen separated by biological material, a construct consisting of multiple layers separated by biological material, wherein one or both layers are comprised of materials selected from at least one of the group consisting of a protein, collagen, MATRIGEL, and a matrix.

36. The method of claim 32 further comprising incubating the substance.

37. The method of claim 32 further comprising forming at least one microfluidic channel that is connected to the microscale feature.

38. The method of claim 32 further comprising locating the substance within or in proximity to a portion of the microfluidic channel.

39. The method of claim 32 further comprising applying, forming, containing, inserting, assembling, making or constituting the substance to, in, or into the device or the microscale feature.

40. The method of claim 32 wherein the adherence, segregation or immobilization of the portion of the biological material provides the at least one pharmacokinetic parameter.

41. The method of claim 32 wherein the microscale feature is selected from at least one of the group consisting of a chamber, a channel, a tube, a well, a scaffold, an inlet, an outlet, a valve, a membrane, a diaphragm, or a compartment.

42. The method of claim 32 wherein the at least one pharmacokinetic parameter is selected from at least one of the group consisting of tissue size ratio, tissue to blood volume ratio, drug residence time, measurement of interactions between cells, liquid residence time, liquid to cell ratios, metabolism by cells, shear stress, flow rate, geometry, the number of cells in the culture device, circulatory transit time, and liquid distribution.

43. A device comprising:

a microscale chamber comprising a biological material and a geometry simulating parts of a living body, wherein the microscale chamber is configured to substantially mimic at least one measurable condition in vivo; and

a substance that is configured to adhere, segregate, or immobilize a portion of the biological material to or within a portion of the device.