DEVICES AND METHODS FOR PHARMACOKINETIC-BASED CELL CULTURE SYSTEM
First Claim
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1. A pharmacokinetic-based microscale culture device, comprising:
- a first microscale chamber containing a first type of cell under conditions where the first type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, 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 under conditions where the second type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for 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 chambers.
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Abstract
Devices, in vitro cell cultures, systems, and methods are provided for microscale cell culture analogous (CCA) device.
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Citations
178 Claims
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1. A pharmacokinetic-based microscale culture device, comprising:
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a first microscale chamber containing a first type of cell under conditions where the first type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, 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 under conditions where the second type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for 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 chambers. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 107, 108, 109, 110, 111)
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35. A pharmacokinetic-based culture system of cells grown in a microscale culture device, comprising:
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a first chamber comprising a first cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in vivo;
a second chamber of different geometry than the first chamber comprising a second cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in vivo;
wherein the first and second chambers are interconnected by fluidic channels; and
an inlet and outlet for recirculation of culture medium. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)
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73. A pharmacokinetic-based microscale culture device, comprising:
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a first microscale chamber containing a cell culture comprising a first type of cell under physiological conditions where the cell culture provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell culture in vivo, wherein the first chamber comprises a first inlet and a first outlet for flow of culture medium; and
a sensor for obtaining signals from the cell culture. - View Dependent Claims (74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106)
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112. A microscale culture device, comprising:
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a first microscale chamber having a geometry simulating a first in vivo interaction with culture medium, wherein the first chamber comprises a first inlet and a first outlet for flow of the culture medium;
a second microscale chamber having a geometry simulating a second in vivo interaction with the culture medium, wherein the second chamber comprises a second inlet and a second outlet for flow of the culture medium; and
a microfluidic channel interconnecting the first and second chambers. - View Dependent Claims (113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124)
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125. A microscale culture device comprising:
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a plurality of chambers connected by fluidic passages, each chamber having a geometry simulating parts of a living body; and
a pump, for circulating culture medium through the chambers to simulate the effects of compounds on the living body. - View Dependent Claims (126, 127, 128, 129, 130, 131, 132, 133, 134)
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135. A microscale culture device, comprising:
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a lung simulating chamber;
a pump;
at least two of a liver simulating chamber, a slowly perfused simulating chamber, a rapidly perfused simulating chamber and a fat simulating chamber coupled in parallel; and
a plurality of microfluidic channels serially coupling the lung simulating chamber, the pump, and the at least two chambers.
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136. A method of forming a microscale culture device, the method comprising:
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forming a first microscale chamber having a geometry simulating a first in vivo interaction with culture medium, wherein the first chamber comprises a first inlet and a first outlet for flow of the culture medium;
forming a second microscale chamber having a geometry simulating a second in vitro interaction with the culture medium, wherein the second chamber comprises a second inlet and a second outlet for flow of the culture medium; and
forming a microfluidic channel interconnecting the first and second chambers. - View Dependent Claims (137, 138, 139)
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140. An array of microscale culture devices comprising:
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a housing for enclosing the devices, each device comprising;
a first microscale chamber having a geometry simulating a first in vivo interaction with culture medium, wherein the first chamber comprises a first inlet and a first outlet for flow of the culture medium; and
channels coupled to the inlets and outlets of the chamber. - View Dependent Claims (141, 142, 143, 144)
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145. A system comprising:
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a first microscale culture device having a plurality of microscale chambers with geometries that simulate a plurality of in vivo interactions with a culture medium, wherein each chamber includes an inlet and an outlet for flow of the culture medium, and a microfluidic channel interconnecting the chambers; and
a control instrument coupled to the first microscale culture device, the control instrument having a computer to acquire data from, and control pharmacokinetic parameters of, the first microscale culture device. - View Dependent Claims (146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158)
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159. A computerized method for dynamically controlling a microscale culture device, the computerized method comprising:
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analyzing data from a plurality of sensors to measure physiological events in a plurality of chambers of the microscale culture device;
regulating fluid flow rates of a culture medium in the chambers of the microscale culture device;
detecting biological or toxicological reactions in the chambers of the microscale culture device; and
upon detection, changing one or more pharmacokinetic parameters of the microscale culture device. - View Dependent Claims (160, 161, 162, 163, 164, 165)
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166. A computer-readable medium having computer-executable instructions stored thereon to perform a method, the method comprising:
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analyzing data from a plurality of sensors to measure physiological events in a plurality of chambers of the microscale culture device;
regulating fluid flow rates of a culture medium in the chambers of the microscale culture device;
detecting biological or toxicological reactions in the chambers of the microscale culture device; and
upon detection, changing one or more pharmacokinetic parameters of the microscale culture device. - View Dependent Claims (167, 168, 169, 170, 171)
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172. A computer comprising:
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a microprocessor, a general memory;
a non-volatile storage element;
an input/output interface that includes an interface to a microscale culture device having one or more sensors; and
computer software executable on the microprocessor to analyze data from the sensors to measure physiological events in a plurality of chambers of the microscale culture device, regulate fluid flow rates of a culture medium in the chambers of the microscale culture device, detect biological or toxicological reactions in the chambers of the microscale culture device, and upon detection, change one or more pharmacokinetic parameters of the microscale culture device. - View Dependent Claims (173, 174, 175, 176, 177, 178)
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Specification