Integrated human organ-on-chip microphysiological systems

• US 9,725,687 B2
• Filed: 12/10/2012
• Issued: 08/08/2017
• Est. Priority Date: 12/09/2011
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Vanderbilt University
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), Vanderbilt University
• Inventors: Goss, Josue A., Cunningham, Robert, Cliffel, David E., McKenzie, Jennifer Robin, Bahinski, Anthony, Block, III, Frank Emmanuel, Wikswo, John P., Samson, Philip C., Parker, Kevin Kit, Hamilton, Geraldine A., Levner, Daniel, Reiserer, Ronald S., McLean, John A., McCawley, Lisa Joy, Markov, Dmitry, Ingber, Donald E., Hinojosa, Christopher David
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US14/362,841
• Publication Number:
  US 20150004077A1
• Time in Patent Office: 1,702 Days
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
• CPC Class Codes: A01N 1/0273 Transport containers A01N1/0268 takes precedence
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: C12M 21/08 : for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 23/16 : Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 23/42 : Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 29/10 : Perfusion
• CPC Class Codes: C12M 35/04 : Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
• CPC Class Codes: C12M 35/08 : Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• CPC Class Codes: 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
• CPC Class Codes: C12M 41/12 : of temperature controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00
• CPC Class Codes: C12M 41/46 : of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: G01N 33/5005 : involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/5082 : Supracellular entities, e.g. tissue, organisms
• CPC Class Codes: G01N 33/5088 : of vertebrates

Abstract

The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

Claims

1. An organ cartridge comprising:

a base substrate including;

a holder and microfluidic connections for at least one organ-chip or one port adapted for the organ-chip disposed thereon; and

at least one fluidic circuit having an inlet and outlet, in connection with the at least one organ chip or the corresponding port,

wherein each of the at least one organ-chip is configured to be removed and separated from the organ cartridge, and the inlet and the outlet of the at least one fluidic circuit are configured to connect to at least one fluid connection external to the organ cartridge.

2. The organ cartridge of claim 1, wherein the organ cartridge fluidically connects to the organ chip, a second organ cartridge, an organ-farm, or an organ-interrogator.

3. The organ cartridge of claim 1, wherein the organ cartridge comprises at least one sensor adapted for monitoring or recording a parameter relating to temperature, metabolic activity, health or culture conditions of cells on the at least one organ chip.

4. The organ cartridge of claim 3, wherein the organ cartridge comprises at least one valve adapted to selectively connect the at least one sensor with at the least one fluidic circuit.

5. The organ cartridge of claim 1, wherein the organ cartridge comprises one or more reservoirs containing sensor washing or calibration fluids.

6. The organ cartridge of claim 1, wherein the organ cartridge comprises at least one microprocessor.

7. The organ cartridge of claim 1, wherein the organ cartridge comprises at least one microprocessor adapted for controlling flow of a fluid through the at least one organ chip.

8. The organ cartridge of claim 1, wherein the organ cartridge comprises at least one microprocessor adapted for controlling the amount of a drug, chemical, or biological challenge agent delivered to the at least one organ chip.

9. The organ cartridge of claim 1, wherein the organ cartridge comprises at least one bubble trap.

10. The organ cartridge of claim 1, wherein the organ cartridge further comprises:

one or more on-board reservoirs containing nutrients; and

at least one on-board waste reservoir adapted to contain effluent from the at least one organ chip.

11. The organ cartridge of claim 1, wherein the inlet and the outlet independently comprise a Luer Lock and wherein the at least one fluidic circuit connects to the organ chip using at least one face-sealing raised surface or an O-ring, the organ cartridge further comprising:

at least one bubble trap in connection with the at least one fluidic circuit and the organ chip disposed on the organ cartridge.

12. The organ cartridge of claim 1, further comprising:

at least one pump in connection with the at least one fluidic circuit;

at least one valve in connection with the at least one fluidic circuit;

at least one micro-clinical analyzer in connection with the at least one fluidic circuit; and

at least one perfusion controller in connection with the at least one fluidic circuit.

13. The organ cartridge of claim 1, wherein the at least one organ chip is configured to mimic at least one physiological function of at least one tissue.