DEVICES AND METHODS FOR PHARMACOKINETIC-BASED CELL CULTURE SYSTEM

• US 20100304355A1
• Filed: 09/08/2006
• Published: 12/02/2010
• 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 Andrew, Shuler, Michael, Meyers, Scott, Baxter, Gregory T., Sin, Aaron
• Application Number:
  US11/530,400
• Publication Number:
  US 20100304355A1
• Time in Patent Office: Days
• US Class Current: 435/3
• 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 heating element that is configured to maintain a desired temperature under a condition of flow of the fluid.

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 heating element configured to control, adjust, or maintain temperature.

3. The device of claim 2 wherein the heating element is configured to provide a value of at least one physiological parameter in vitro that is comparable to a value of at least one physiological parameter found in vivo.

4. The device of claim 2 wherein the heating element is configured to regulate the temperature of the fluid.

5. The device of claim 2 wherein the heating element is a heating coil that is located in or external to the device.

6. The device of claim 2 wherein the heating element is controlled by a processor.

7. The device of claim 2 further comprising a temperature probe that is located in or external to the device.

8. The device of claim 7 wherein the temperature of fluid is regulated based on data from the temperature probe.

9. The device of claim 2 wherein the heating element maintains fluid at a temperature of 37 degrees Celsius.

10. The device of claim 2 further comprising at least one microfluidic channel connected to the microscale feature.

11. The device of claim 2 wherein the heating element is formed in, contained in, assembled in, made in, constituted in or inserted in or near the microfluidic channel.

12. The device of claim 2 wherein the heating element is formed in, contained in, assembled in, made in, constituted in or inserted in or near the device or the microscale feature.

13. The device of claim 2 wherein the value of at least one pharmacokinetic parameter in vitro is within 25% to the value of at least one pharmacokinetic parameter found in vivo.

14. The device of claim 2 wherein the characteristics of fluid flow are based on a mathematical model.

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

PBPK”

) model.

16. 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.

17. 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.

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

19. 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.

20. The device of claim 2 further comprising at least a second microscale feature dimensioned to maintain the same or different biological material under conditions that provide a value of at least a second pharmacokinetic parameter in vitro comparable to a value of at least a second pharmacokinetic parameter found in vivo.

21. The device of claim 2 further comprising a system of elements that facilitate, complement, optimize, elaborate upon, or extend the functionality or utility of the device.

22. The device of claim 21 wherein an element of the system may be internal to, integrated with, or external to the device.

23. The device of claim 21 wherein the element of the system may comprise one or more of the group consisting of a liquid, a culture medium, a housing, a fluid interconnect, a biological material, a heating element, a pump, a microprocessor, a fluidic reservoir, a gas exchange mechanism, tubing to provide fluidic connection and conduction between and among the device and the one or more elements of the system, a sensor, a signal transducer, a data storage device, an atmospheric control unit, an incubator, an adherent material, a two-dimensional culture matrix, a three-dimensional culture matrix, an adherent material, operating software, analytic software, an information database, readout instrumentation, a debubbler, a biological barrier, an assay, a fluidic interface, and the device itself.

24. The device of claim 2 further comprising:

a housing that encloses at least the microscale feature;

a fluidic interface on or within the device;

a fluidic reservoir in communication with the fluidic interface; and

a pump that is configured to pump a fluid through the fluidic interface.

25. The device of claim 2 further comprising:

a sensor that is configured to obtain data related to the device; and

a processor that is configured to process the data acquired by the sensor.

26. 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

maintaining a desired temperature under a condition of flow of the fluid.

27. 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

controlling, adjusting, or maintaining temperature with a heating element.

28. The method of claim 27 wherein the heating element provides a value of at least one physiological parameter in vitro that is comparable to a value of at least one physiological parameter found in vivo.

29. The method of claim 27 wherein the heating element is located in or external to a device that has the microscale feature.

30. The method of claim 27 further comprising controlling the heating element with a processor.

31. The method of claim 27 further comprising monitoring the temperature of the fluid with a temperature probe that is located in or external to the microscale feature.

32. The method of claim 31 wherein the adjusting of the temperature is based on data from the temperature probe.

33. The method of claim 27 further comprising maintaining the fluid at a temperature of 37 degrees Celsius.

34. The method of claim 27 further comprising forming, containing, inserting, assembling, making or constituting the heating element in or into a device.

35. The device of claim 27 further comprising locating the heating element within a portion of a microfluidic channel.

36. The method of claim 27 further comprising flowing fluid through the microscale feature.

37. The method of claim 27 wherein the flow of fluid through, or in proximity to, the microscale feature provides the at least one pharmacokinetic parameter.

38. The method of claim 27 wherein the value of at least one pharmacokinetic parameter in vitro is within 25% to the value of at least one pharmacokinetic parameter found in vivo.

39. The method of claim 27 wherein the characteristics of fluid flow are based on a mathematical model.

40. The method of claim 39 wherein the mathematical model is a physiologically based pharmacokinetic (“

PBPK”

) model.

41. The method of claim 27 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 value, a membrane, a diaphragm, or a compartment.

42. The method of claim 27 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. The method of claim 27 further comprising combining a system of elements that facilitate, complement, optimize, elaborate upon, or extend the functionality or utility of the microscale feature.

44. The method of claim 43 wherein an element of the system may be internal to, integrated with, or external to the microscale feature.

45. The method of claim 43 wherein the element of the system may comprise one or more of the group consisting of a liquid, a culture medium, a housing, a fluid interconnect, a biological material, a heating element, a pump, a microprocessor, a fluidic reservoir, a gas exchange mechanism, tubing to provide fluidic connection and conduction between and among the device and the one or more elements of the system, a sensor, a signal transducer, a data storage device, an atmospheric control unit, an incubator, an adherent material, a two-dimensional culture matrix, a three-dimensional culture matrix, an adherent material, operating software, analytic software, an information database, readout instrumentation, a debubbler, a biological barrier, an assay, a fluidic interface, and the device itself.

46. The method of claim 27 further comprising:

enclosing at least the microscale feature with a housing;

connecting a fluidic reservoir to a fluidic interface that is on or in proximity to the microscale feature; and

a pump that is configured to pump a fluid through the fluidic interface.

47. The method of claim 27 further comprising:

obtaining data with a sensor; and

processing the data acquired by the sensor with a processor.

48. A device comprising:

means for 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

means for adjusting the temperature with a heating element.

49. 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, forming, or providing for a heating element.

50. A method comprising:

means for 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

means for adding, forming, or providing for a heating element.

51. 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 in vivo condition in vivo; and

a heating element configured to control, adjust, or maintain temperature.