# US 2019/0169557 A1 · Perfusion manifold assembly

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- Number: US 2019/0169557 A1
- Document ID: US20190169557A1
- Status: Published application
- Kind: A1
- Application number: 16/226,229
- Filed: 2018-12-19
- Published: 2019-06-06
- Earliest claimed: 2015-08-26
- Assignees: Emulate, Inc.
- Applicants: EMULATE, Inc.
- Inventors: Daniel Levner; Josiah Daniel Sliz; Christopher David Hinojosa; Guy Robert Thompson, II; Petrus Wilhelmus Martinus van Ruijven; Matthew Daniel Solomon; Christian Alexander Potzner; Patrick Sean Tuohy; Joshua Gomes; Norman Wen; Jacob Freake; Doug Sabin
- Web page: https://patentgrep.com/patent/US20190169557A1

## CPC

- C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)}
- A01N 1/122: Preservation or perfusion media
- A01N 1/143: for organ perfusion
- B01L 3/502707: {characterised by the manufacture of the container or its components}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 9/527: {for microfluidic devices, e.g. used for lab-on-a-chip}
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 23/38: {Caps; Covers; Plugs; Pouring means}
- C12M 23/40: {Manifolds; Distribution pieces (fluid transfer means B01L3/563)}
- C12M 23/42: {Integrated assemblies, e.g. cassettes or cartridges}
- C12M 29/10: {Perfusion}
- C12M 33/12: {by pressure}
- C12M 35/04: {Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli}
- C12M 41/40: {of pressure}
- C12M 41/48: {Automatic or computerized control (automatic analysis G01N35/00)}
- C12N 5/0602: {Vertebrate cells}
- B01L 2200/025: Align devices or objects to ensure defined positions relative to each other
- B01L 2200/027: for microfluidic devices
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2300/0681: Filter
- B01L 2300/0887: Laminated structure
- B01L 2300/123: Flexible; Elastomeric
- B01L 2300/14: Means for pressure control
- B01L 2300/161: Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
- B01L 2300/165: Specific details about hydrophobic, oleophobic surfaces
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/06: Valves, specific forms thereof
- C12N 2521/00: Culture process characterised by the use of hydrostatic pressure, flow or shear forces
- 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}
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A perfusion manifold assembly is described that allows for perfusion of a microfluidic device, such as an organ on a chip microfluidic device comprising cells that mimic cells in an organ in the body, that is detachably linked with said assembly so that fluid enters ports of the microfluidic device from a fluid reservoir, optionally without tubing, at a controllable flow rate. Drop-to-drop connection schemes are described for putting a microfluidic device in fluidic communication with a fluid source or another microfluidic device, including but not limited to, putting a microfluidic device in fluidic communication with the perfusion manifold assembly.

## Claims

### Claim at position 1

1-13. (canceled)

### Claim 14

A system, comprising:
a) a perfusion manifold assembly, comprising i) one or more fluid reservoirs, ii) a fluidic backplane positioned under, and in fluidic communication with, said fluid reservoirs, said fluidic backplane comprising fluid channels that terminate at fluid outlet ports, and iii) a skirt having a guide mechanism; and
b) a microfluidic device positioned in a carrier, said carrier detachably engaging said guide mechanism of said skirt, said microfluidic device comprising i) microchannels in fluidic communication with said perfusion manifold assembly via ii) one or more inlet ports on a iii) mating surface, wherein said one or more fluid inlet ports of said microfluidic device are positioned against said one or more fluid outlet ports of said skirt of said perfusion manifold assembly under conditions such that fluid flows from said fluid reservoirs of said perfusion manifold assembly through said one or more fluid outlet ports into said one or more fluid inlet ports of said microfluidic device.

### Claim 15 (depends on 14)

The system of claim 14, wherein said microfluidic device comprises living cells perfused with fluid from said fluid reservoirs.

### Claim 16 (depends on 14)

The system of claim 14, wherein said microfluidic device comprises at least two different cell types that function together in a manner that mimic one or more functions of cells in an organ in the body.

### Claim 17 (depends on 16)

The system of claim 16, wherein the microfluidic device comprises a membrane having top and bottom surfaces, said top surface comprising a first cell type, said bottom surface comprises a second cell type.

### Claim 18 (depends on 17)

The system of claim 17, wherein said first cell type is epithelial cells and said second cell type is endothelial cells.

### Claim 19 (depends on 17)

The system of claim 17, wherein said membrane is porous.

### Claim 20 (depends on 14)

The system of claim 14, wherein said fluidic backplane comprises a fluid resistor.

### Claim 21 (depends on 14)

The system of claim 14, wherein said guide mechanism comprises one or more side tracks.

### Claim 22 (depends on 21)

The system of claim 21, wherein the carrier comprises one or more outer edges, said outer edges detachably engaging said one or more side tracks of said skirt.

### Claim 23 (depends on 14)

The system of claim 14, wherein said carrier further comprises a locking mechanism for restricting movement of the carrier when said one or more fluid inlet ports of said microfluidic device are positioned against said one or more fluid outlet ports of said perfusion manifold assembly.

### Claim at position 12

24-44. (canceled)

### Claim 45

A system, comprising:
a) a perfusion manifold assembly, comprising i) one or more fluid reservoirs, ii) a fluidic backplane positioned under, and in fluidic communication with, said fluid reservoirs, said fluidic backplane comprising fluid channels that terminate at fluid outlet ports, and iii) a guide mechanism; and
b) a microfluidic device positioned in a carrier, said carrier detachably engaging said guide mechanism, said microfluidic device comprising i) microchannels in fluidic communication with said perfusion manifold assembly via ii) one or more inlet ports on a iii) mating surface, wherein said one or more fluid inlet ports of said microfluidic device are positioned against said one or more fluid outlet ports of said skirt of said perfusion manifold assembly under conditions such that fluid flows from said fluid reservoirs of said perfusion manifold assembly through said one or more fluid outlet ports into said one or more fluid inlet ports of said microfluidic device.

### Claim 46 (depends on 45)

The system of claim 45, wherein said microfluidic device comprises living cells perfused with fluid from said fluid reservoirs.

### Claim 47 (depends on 45)

The system of claim 45, wherein said microfluidic device comprises at least two different cell types that function together in a manner that mimic one or more functions of cells in an organ in the body.

### Claim 48 (depends on 47)

The system of claim 47, wherein the microfluidic device comprises a membrane having top and bottom surfaces, said top surface comprising a first cell type, said bottom surface comprises a second cell type.

### Claim 49 (depends on 48)

The system of claim 48, wherein said first cell type is epithelial cells and said second cell type is endothelial cells.

### Claim 50 (depends on 48)

The system of claim 48, wherein said membrane is porous.

### Claim 51 (depends on 45)

The system of claim 45, wherein said fluidic backplane comprises a fluid resistor.

### Claim 52 (depends on 45)

The system of claim 45, wherein said guide mechanism comprises one or more side tracks.

### Claim 53 (depends on 52)

The system of claim 52, wherein the carrier comprises one or more outer edges, said outer edges detachably engaging said one or more side tracks of said guide mechanism.

### Claim 54 (depends on 45)

The system of claim 45, wherein said carrier further comprises a locking mechanism for restricting movement of the carrier when said one or more fluid inlet ports of said microfluidic device are positioned against said one or more fluid outlet ports of said perfusion manifold assembly.