Devices and methods for pharmacokinetic-based cell culture systems

Abstract

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

1 . A microscale culture device, comprising: 
 a first microscale chamber dimensioned to maintain biological material under conditions that provide a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable 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 measurable parameter in vitro that is comparable to a value of at least one measurable 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 pump that is configured to pump a fluid through the first and second microscale chambers; and    a processor coupled to the device.    
   
   
       2 . The device of  claim 1  wherein the processor is configured to control the device.  
   
   
       3 . The device of  claim 2  wherein controlling the device comprises providing a value of at least one measurable parameter in the device.  
   
   
       4 . The device of  claim 2  wherein the processor is configured to control at least the pump.  
   
   
       5 . The device of  claim 2  wherein the processor is configured to process data obtainable from the device.  
   
   
       6 . The device of  claim 5  wherein processing the data comprises at least one of the group consisting of deriving the data, storing the data, analyzing the data, transmitting the data and presenting the data.  
   
   
       7 . The device of  claim 5  further comprising a sensor configured to obtain data from the device.  
   
   
       8 . The device of  claim 2  wherein controlling the device comprises regulating fluid flow rate.  
   
   
       9 . The device of  claim 8  wherein regulating fluid flow rate maintains at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.  
   
   
       10 . The device of  claim 1  wherein the measurable parameter comprises a pharmacokinetic parameter.  
   
   
       11 . The device of  claim 1  wherein the processor is comprised of components selected from at least one of the group consisting of a computer, a microprocessor, a general memory, a non-volatile storage element, an input/output interface, and a computer software.  
   
   
       12 . A device comprising: 
 at least one microscale feature dimensioned to maintain biological material under conditions that provide a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter found in vivo;    a pump that is configured to pump a fluid through the microscale feature; and    a processor coupled to the device.    
   
   
       13 . The device of  claim 12  wherein the processor is configured to control the device.  
   
   
       14 . The device of  claim 13  wherein controlling the device comprises providing a value of at least one measurable parameter in the device.  
   
   
       15 . The device of  claim 12  wherein the processor is configured to control at least the pump.  
   
   
       16 . The device of  claim 12  wherein the processor is configured to process data obtainable from the device.  
   
   
       17 . The device of  claim 15  wherein processing the data comprises at least one of the group consisting of deriving the data, storing the data, analyzing the data, transmitting the data and presenting the data.  
   
   
       18 . The device of  claim 12  further comprising a sensor configured to obtain data from the device.  
   
   
       19 . The device of  claim 12  wherein the processor is configured to regulate a temperature of the fluid.  
   
   
       20 . The device of  claim 12  wherein the processor is configured to regulate fluid flow rate.  
   
   
       21 . The device of  claim 20  wherein regulating fluid flow rate maintains at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.  
   
   
       22 . The device of  claim 20  wherein the characteristics of fluid flow are based on a mathematical model.  
   
   
       23 . The device of  claim 22  wherein the mathematical model is a physiologically based pharmacokinetic (“PBPK”) model.  
   
   
       24 . The device of  claim 12  wherein the measurable parameter comprises a pharmacokinetic parameter.  
   
   
       25 . The device of  claim 12  wherein the processor is configured to detect biological or toxicological reactions in the device, and upon detection, change one or more of the measurable parameters.  
   
   
       26 . The device of  claim 12  wherein the value of at least one measurable parameter in vitro is within 25% to the value of at least one measurable parameter found in vivo.  
   
   
       27 . The device of  claim 12  wherein the processor is comprised of components selected from at least one of the group consisting of a computer, a microprocessor, a general memory, a non-volatile storage element, an input/output interface, and a computer software.  
   
   
       28 . The device of  claim 12  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.  
   
   
       29 . The device of  claim 12  further comprising a biological material.  
   
   
       30 . The device of  claim 29  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, a cell, 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.  
   
   
       31 . The device of  claim 12  wherein the microscale feature contains circulating, immobilized, or adherent biological material.  
   
   
       32 . The device of  claim 12  wherein the at least one measurable parameter is selected from at least one of the group consisting of 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, the number of cells in the culture device, circulatory transit time, and liquid distribution.  
   
   
       33 . The device of  claim 12  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 measurable parameter in vitro comparable to a value of at least a second measurable parameter found in vivo.  
   
   
       34 . The device of  claim 12  further comprising a system of elements that facilitate, complement, optimize, elaborate upon, or extend the functionality or utility of the device.  
   
   
       35 . The device of  claim 34  wherein an element of the system may be internal to, integrated with, or external to the device.  
   
   
       36 . The device of  claim 35  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.  
   
   
       37 . The device of  claim 12  further comprising: 
 a housing that encloses at least the microscale feature; and    a fluidic reservoir in communication with the microscale feature.    
   
   
       38 . The device of  claim 12  further comprising a fluidic interface.  
   
   
       39 . The device of  claim 38  wherein the fluidic interface couples the device directly or indirectly to a bioanalytic instrument.  
   
   
       40 . The device of  claim 38  wherein the interface is coupled to and physically integrated with at least one other element of the device.  
   
   
       41 . The device of  claim 38  wherein the interface is coupled to but not physically integrated with at least one other element of the device.  
   
   
       42 . 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 measurable parameter in vitro that is comparable to a value of at least one measurable 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 measurable parameter in vitro that is comparable to a value of at least one measurable 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;    pumping the fluid; and    regulating the pumping of the fluid with a processor.    
   
   
       43 . The method of  claim 42  wherein the processor regulates the pumping of the fluid in a manner that maintains a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.  
   
   
       44 . The method of  claim 42  wherein the measurable parameter comprises a pharmacokinetic parameter  
   
   
       45 . A method comprising: 
 maintaining biological material with at least one microscale feature under conditions that provide a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter found in vivo; and    pumping a fluid in or through the at least one microscale feature; and    regulating the pumping of the fluid in a manner that maintains a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.    
   
   
       46 . The method of  claim 45 , wherein the measurable parameter comprises a pharmacokinetic parameter.  
   
   
       47 . A device comprising: 
 means for maintaining biological material with at least one microscale feature under conditions that provide a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter found in vivo;    means for pumping a fluid in or through the at least one microscale feature; and    means for regulating the pumping of the fluid.    
   
   
       48 . The device of  claim 47  wherein the measurable parameter comprises a pharmacokinetic parameter.  
   
   
       49 . The device of  claim 47  wherein the means for regulating the pumping of the fluid regulates pumping in a manner that maintains at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.  
   
   
       50 . A method comprising: 
 forming a microscale feature that is dimensioned to maintain biological material under conditions that provide a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter found in vivo;    providing a pump that is configured to pump fluid through the microscale chamber; and    providing a processor coupled to at least one of the microscale feature or the pump.    
   
   
       51 . The method of  claim 50  wherein the processor is configured to regulate the pumping of the fluid.  
   
   
       52 . The method of  claim 51  wherein pumping of the fluid comprises pumping in a manner that maintains a value of at least one measurable parameter in vitro that is comparable to a value of at least one measurable parameter obtained in vivo.  
   
   
       53 . The method of  claim 50  wherein the measurable parameter comprises a pharmacokinetic parameter.  
   
   
       54 . A microscale culture device comprising: 
 a microscale feature comprising a biological material and a feature geometry, wherein the microscale feature is configured to substantially mimic in vitro at least one measurable condition in vivo;    a pump that is configured to pump fluid through the microscale chamber; and    a processor coupled to the device.    
   
   
       55 . The device of  claim 54  wherein the processor is configured to control the device.  
   
   
       56 . The device of  claim 55  wherein controlling the device comprises providing at least one measurable in vivo condition to the biological material.  
   
   
       57 . The device of  claim 54  wherein the processor is configured to process data obtainable from the device.  
   
   
       58 . The device of  claim 54  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, a cell, 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.