# US 8,785,178 B2 · Perifusion device > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,785,178 B2 - Document ID: US8785178B2 - Status: Granted - Kind: B2 - Application number: 11/653,193 - Filed: 2007-01-12 - Published: 2008-07-17 - Granted: 2014-07-22 - Earliest claimed: 2007-01-12 - Assignees: Biorep Technologies, Inc.; University of Miami - Applicants: Ramon E. Poo; Camillo Ricordi; Felipe Echeverri; Over Cabrera; Per-Olof Berggren - Inventors: Ramon E. Poo; Camillo Ricordi; Felipe Echeverri; Over Cabrera; Per-Olof Berggren - Web page: https://patentgrep.com/patent/US8785178B2 ## CPC - C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)} - C12M 23/12: {Well or multiwell plates (C12M25/04 takes precedence)} - C12M 29/10: {Perfusion} - C12M 33/10: {by centrifugation (centrifuges in general B04B); Cyclones (cyclones in general B04C)} - C12M 35/04: {Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli} - C12M 41/00: {Means for regulation, monitoring, measurement or control, e.g. flow regulation (controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N)} - C12M 41/14: {Incubators; Climatic chambers (per se B01L1/00)} - C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability} - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract A perifusion device includes at least one sample container for cells, the sample container having an inlet and an outlet. The container receives test liquid through the inlet and discharges the liquid through the outlet. A receptacle housing has a plurality of receptacles for receiving fluid from the outlet of the sample container. A drive is connected to the receptacle housing for moving the receptacle housing such that liquid samples are collected sequentially from the outlet of the sample containers. A computer can be provided to control movement of the receptacle housing at predetermined times, and to record data identifying liquid samples in the receptacles. The test liquid includes at least one stimuli for the cells, which can be the presence, absence, or concentration of a compound in the liquid, or a physical property of the liquid such as temperature. The liquid collected in the receptacles is analyzed to determine the response of the cells to the stimuli. ## Claims ### Claim 1 A perifusion device, comprising: a plurality of sample containers; the sample containers having a liquid inlet and a liquid outlet, the containers receiving liquid through the inlet and discharging liquid through the outlet; a plurality of liquid sources for supplying a plurality of liquids to said sample containers; a plurality of manifolds disposed between the liquid sources and the sample containers, each manifold having a plurality of manifold inlets and at least one manifold outlet, each liquid source being in fluid connection to at least one manifold inlet, each manifold outlet being in fluid communication with a plurality of manifold inlets, each manifold outlet being in fluid connection with a liquid inlet of a sample container; a plurality of valves, said valves controlling liquid flow from the liquid sources through the manifold inlets; at least one pump for pumping liquid from the manifold outlets to respective sample containers; a receptacle housing having a plurality of receptacles for receiving fluid from the liquid outlets of the sample containers, said plurality of receptacles being positioned in said receptacle housing such that different receptacles receive samples from different liquid outlets of each of said sample containers; a drive connected to the receptacle housing for moving said receptacle housing such that samples from the outlet are collected in said plurality of receptacles; and, a programmable controller that is programmed to operate the driver to move the receptacles at predetermined times, to operate the valves, and to record the position of the valves and the receptacles as a function of time so as to correlate the liquids that are supplied to each sample container from the plurality of liquid sources with the liquid samples that are received by the receptacles from the sample containers. ### Claim 2 (depends on 1) The perifusion device of claim 1, wherein said receptacles are arranged in rows and columns. ### Claim 3 (depends on 2) The perifusion device of claim 2, wherein said liquid outlets of said sample containers are aligned in a row, said rows of receptacles being aligned with said row of liquid outlets to receive samples from said sample containers, and whereby movement of said receptacle housing by said drive will cause successive receptacles in said columns to receive successive samples from said sample containers. ### Claim 4 (depends on 3) The perifusion device of claim 3, wherein said receptacles are wells. ### Claim 5 (depends on 1) The perifusion device of claim 1, wherein said sample containers are columns. ### Claim 6 (depends on 1) The perifusion device of claim 1, wherein said sample containers are packed with substrate. ### Claim 7 (depends on 6) The perifusion device of claim 6, wherein said substrate comprises at least one selected from the group consisting of beads and gel. ### Claim 8 (depends on 1) The perifusion device of claim 1, wherein said pump controls the volumetric flow rate through said container. ### Claim 9 (depends on 1) The perifusion device of claim 1, wherein said pump is a peristaltic pump. ### Claim 10 (depends on 1) The perifusion device of claim 1, further comprising at least one sensor for sensing a characteristic of the fluid. ### Claim 11 (depends on 1) The perifusion device of claim 1, comprising at least one sensor upstream of the sample and at least one sensor downstream of the sample. ### Claim 12 (depends on 1) The perifusion device of claim 1, wherein at least one of said liquid sources comprises a cell stimulus compound, said compound being at least one selected from the group consisting of carbohydrate, lipid, and peptide. ### Claim 13 (depends on 1) The perifusion device of claim 1, wherein at least one of said liquid sources comprises a cell stimulus compound, said cell stimulus compound comprising a drug which stimulates cell behavior in some detectable way. ### Claim 14 (depends on 1) The perifusion device of claim 1, wherein said receptacle housing is a tray. ### Claim 15 (depends on 14) The perifusion device of claim 14, wherein said tray comprises a plurality of receptacles. ### Claim 16 (depends on 1) The perifusion device of claim 1, further comprising at least one analytical device for detecting at least one analyte in said liquid. ### Claim 17 (depends on 1) The perifusion device of claim 1, further comprising at least one temperature controller for controlling the temperature of said liquid flowing through said sample container. ### Claim 18 (depends on 1) The perifusion device of claim 1, wherein said plurality of valves control flow of different test liquids to different ones of said manifold inlets that are in fluid communication with the same manifold outlet, said manifold outlets directing flow to one of said sample containers. ### Claim 19 (depends on 1) The perifusion device of claim 1, wherein said sample container comprises a main body portion and a collar, said main body portion dimensioned to fit within a microcentrifuge tube, said collar dimensioned to abut an end of the microcentrifuge tube.