Devices and methods for pharmacokinetic-based cell culture system

Abstract

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

1 . A method for producing a biological product comprising: 
 providing a culture device that contains a culture medium, and a cell that generates a biological product wherein the culture device maintains the cell within 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, and wherein the first microscale chamber comprises a first inlet and a first outlet for flow of the culture medium.    
     
     
         2 . The method of  claim 1 , wherein the cell is a host cell genetically engineered to produce an exogenous gene product.  
     
     
         3 . The method of  claim 1 , wherein the biological product is a growth factor, regulatory factor, peptide hormone, or antibody.  
     
     
         4 . The method of  claim 1 , further comprising isolating the biological product from the culture medium using a standard isolation technique.  
     
     
         5 . The method of  claim 4 , wherein the isolation technique is HPLC, column chromatography, or electrophoresis.  
     
     
         6 . A culture device comprising: 
 a biological material that generates a biological product;    a fluid; and    at least one microscale feature that is configured to maintain the 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.    
     
     
         7 . The device of  claim 6  wherein the biological product selected from at least one of the group consisting of a growth factor, a regulatory factor, a peptide a hormone, and an antibody.  
     
     
         8 . The device of  claim 6  further comprising an isolator that isolates the biological product from the fluid.  
     
     
         9 . The method of  claim 8  wherein the isolation technique is selected from at least one of the group consisting of HPLC, column chromatography, and electrophoresis.  
     
     
         10 . The device of  claim 6  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.  
     
     
         11 . The device of  claim 10  wherein the mathematical model is a physiologically-based pharmacokinetic (“PBPK”) model.  
     
     
         12 . The device of  claim 6  further comprising at least a second microscale feature dimensioned to maintain 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.  
     
     
         13 . The device of  claim 6  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.  
     
     
         14 . The device of  claim 6  wherein the biological material is circulating, immobilized, or adherent.  
     
     
         15 . The device of  claim 6  further comprising an array of devices wherein the devices operate separately from and in parallel with one another.  
     
     
         16 . The device of  claim 6  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 device, circulatory transit time, and liquid distribution.  
     
     
         17 . The device of  claim 6  wherein a portion of the microscale feature is coated to facilitate attachment, segregation or immobilization of the biological material with at least one selected from the group consisting of a protein, collagen, poly-lysine, and MATRIGEL, a hydrogel, a scaffold, a matrix, a construct consisting of multiple layers of collagen separated by biological material, and 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.  
     
     
         18 . The device of  claim 6  further comprising: 
 a housing that encloses at least the microscale feature, the fluid and the biological material;    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.    
     
     
         19 . The device of  claim 6  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.    
     
     
         20 . A method for producing a biological product comprising providing a culture device with a biological material that generates a biological product and a culture medium with a first microscale feature that is configured to maintain the biological product 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.  
     
     
         21 . A device for producing a biological product comprising means for providing a culture device with a biological material that generates a biological product and a culture medium wherein the means maintains the biological material within a first 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 obtained in vivo.  
     
     
         22 . A culture device comprising: 
 a biological material that generates a biological product;    a fluid; and    a microscale chamber for maintaining the biological material comprising a geometry simulating parts of a living body, wherein the microscale chamber is configured to substantially mimic at least one measurable condition in vivo.