# US 12,595,450 B2 · Dynamic multi organ plate

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- Number: US 12,595,450 B2
- Document ID: US12595450B2
- Status: Granted
- Kind: B2
- Application number: 17/102,043
- Filed: 2020-11-23
- Published: 2021-03-18
- Granted: 2026-04-07
- Earliest claimed: 2014-03-21
- Assignees: LifeNet Health
- Applicants: LifeNet Health
- Inventors: James McKim
- Web page: https://patentgrep.com/patent/US12595450B2

## CPC

- C12M 23/12: {Well or multiwell plates (C12M25/04 takes precedence)}
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 23/58: {Reaction vessels connected in series or in parallel (combinations of bioreactors with other apparatus, C12M43/00)}
- C12M 29/00: {Means for introduction, extraction or recirculation of materials, e.g. pumps (pumps per se F04B)}
- C12M 29/04: {Filters; Permeable or porous membranes or plates, e.g. dialysis}
- C12N 5/0697: {Artificial constructs associating cells of different lineages, e.g. tissue equivalents (blood vessels C12N5/0691)}
- 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}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are dynamic multi-organ plates comprising two or more wells, wherein the wells are configured for cell or tissue culture growth; at least one transwell tube in fluid communication with the two or more wells; and a pump in fluid communication with the at least one transwell tube.

## Claims

### Claim 1

A fluidic system for analyte transfer without volume exchange between three or more wells containing human tissue in a plate comprising:
a plate comprising three or more wells, wherein the three or more wells comprise a first well and a last well, wherein the wells are in fluid communication with each other and at least three of the three or more wells are configured for growth of human cells in a culture media;
two or more transwell tubes connecting the three or more wells;
tubing inside the wells being in fluid communication with the transwell tubes permitting a fluid to be pumped through the three or more wells, wherein the tubing comprises dialysis membrane allowing passage of an analyte to diffuse across the tubing into or out of the three or more wells without volume exchange, whereby the human cells are exposed to the analyte, wherein the fluidic system is configured to permit fluid flow through a well comprising gastrointestinal tissue and/or cells prior to fluid flow through a well comprising liver tissue and/or cells; and wherein at least one of the wells comprises an outer shell, an insert, and a fluid space disposed therebetween, the outer shell being a solid piece and defining a shape of the well and the insert comprising a semipermeable wall defining an interior of the well, the semipermeable wall configured to allow for diffusion of chemicals, gasses, and fluids between the fluid space and the interior of the well, wherein the fluid space is in fluid communication with the inlet and outlet tubes;
an inlet tube in fluid communication with the tubing inside the first well;
an outlet tube in fluid communication with the tubing inside the last well; and
a pump connected to the inlet tube, wherein the pump pumps the fluid into, through and out of the three or more wells via the inlet tube, the tubing, the transwell tubes, and the outlet tube.

### Claim 2 (depends on 1)

The fluidic system of claim 1, wherein one of the wells comprises kidney tissue and/or cells.

### Claim 3 (depends on 1)

The fluidic system of claim 1, wherein the fluid is blood or a blood simulator.

### Claim 4 (depends on 1)

The fluidic system of claim 1, wherein the culture media in each well is isolated from the culture media of other wells.

### Claim 5 (depends on 1)

The fluidic system of claim 1, wherein test materials and their metabolites move between wells.

### Claim 6 (depends on 1)

The fluidic system of claim 1, wherein the system is configured to allow introduction of exogenous substances, said exogenous substances comprising drugs, proteins, or chemicals.

### Claim 7 (depends on 1)

The fluidic system of claim 1, wherein aliquots of the fluid are taken.

### Claim 8

A fluidic system for analyte transfer without volume exchange between three or more wells containing human tissue in a plate comprising:
a plate comprising three or more wells, wherein the three or more wells comprise a first well and a last well, wherein the wells are in fluid communication with each other and at least three of the three or more wells are configured for growth of human cells in a culture media;
two or more transwell tubes connecting the three or more wells;
tubing inside the wells being in fluid communication with the transwell tubes permitting a fluid to be pumped through the three or more wells, wherein the tubing comprises dialysis membrane allowing passage of an analyte to diffuse across the tubing into or out of the three or more wells without volume exchange, whereby the human cells are exposed to the analyte, wherein the fluidic system is configured to permit fluid flow through a well comprising gastrointestinal tissue and/or cells prior to fluid flow through a well comprising liver tissue and/or cells; and wherein at least one of the wells comprises an outer shell, an insert, and a fluid space disposed therebetween, the outer shell being a solid piece and defining a shape of the well and the insert comprising a semipermeable wall defining an interior of the well, the semipermeable wall configured to allow for diffusion of chemicals, gasses, and fluids between the fluid space and the interior of the well, wherein the fluid space is in fluid communication with the inlet and outlet tubes;
an inlet tube in fluid communication with the tubing inside the first well;
an outlet tube in fluid communication with the tubing inside the last well;
a pump connected to the inlet tube, wherein the pump pumps the fluid into, through and out of the three or more wells via the inlet tube, the tubing, the transwell tubes, and the outlet tube; and
wherein the transwell tubes are arranged between the wells to permit bidirectional fluid flow between the wells.

### Claim 9 (depends on 8)

The fluidic system of claim 8, wherein one of the wells comprises kidney tissue and/or cells.

### Claim 10 (depends on 8)

The fluidic system of claim 8, wherein the fluid is blood or a blood simulator.

### Claim 11 (depends on 8)

The fluidic system of claim 8, wherein the culture media in each well is isolated from the culture media of other wells.

### Claim 12 (depends on 8)

The fluidic system of claim 8, wherein test materials and their metabolites move between wells.

### Claim 13 (depends on 8)

The fluidic system of claim 8, wherein the system is configured to allow introduction of exogenous substances, said exogenous substances comprise drugs, proteins, or chemicals.

### Claim 14 (depends on 8)

The fluidic system of claim 8, wherein aliquots of the fluid are taken.

### Claim 15

A fluidic system for analyte transfer without volume exchange between three or more wells containing human tissue in a plate comprising:
a plate comprising three or more wells, wherein the three or more wells comprise a first well and a last well, wherein the wells are in fluid communication with each other and at least three of the three or more wells are configured for growth of human cells in a culture media;
two or more transwell tubes connecting the three or more wells;
tubing inside the wells being in fluid communication with the transwell tubes permitting a fluid to be pumped through the three or more wells, wherein the tubing comprises gaps of dialysis membrane allowing passage of an analyte to diffuse across the gaps of dialysis membrane into or out of the at least one well comprising the gaps of dialysis membrane without volume exchange, whereby the human cells are exposed to the analyte, wherein the fluidic system is configured to permit fluid flow through a well comprising gastrointestinal tissue and/or cells prior to fluid flow through a well comprising liver tissue and/or cells, and wherein one of the wells comprises kidney tissue and/or cells;
an inlet tube in fluid communication with the tubing inside the first well;
an outlet tube in fluid communication with the tubing inside the last well; and
a pump connected to the inlet tube, wherein the pump pumps the fluid into, through and out of the three or more wells via the inlet tube, the tubing, the transwell tubes, and the outlet tube; and
wherein the wells comprising the gastrointestinal tissue and/or cells, the liver tissue and/or cells, and the kidney tissue and/or cells comprise the tubing comprising gaps of dialysis membrane.

### Claim 16

A fluidic system for analyte transfer without volume exchange between three or more wells containing human tissue in a plate comprising:
a plate comprising three or more wells, wherein the three or more wells comprise a first well and a last well, wherein the wells are in fluid communication with each other and at least three of the three or more wells are configured for growth of human cells in a culture media;
two or more transwell tubes connecting the three or more wells;
tubing inside the wells being in fluid communication with the transwell tubes permitting a fluid to be pumped through the three or more wells, wherein the tubing comprises gaps of dialysis membrane allowing passage of an analyte to diffuse across the gaps of dialysis membrane into or out of the at least one well comprising the gaps of dialysis membrane without volume exchange, whereby the human cells are exposed to the analyte, wherein the fluidic system is configured to permit fluid flow through a well comprising gastrointestinal tissue and/or cells prior to fluid flow through a well comprising liver tissue and/or cells, and wherein one of the wells comprises kidney tissue and/or cells;
an inlet tube in fluid communication with the tubing inside the first well;
an outlet tube in fluid communication with the tubing inside the last well; and
a pump connected to the inlet tube, wherein the pump pumps the fluid into, through and out of the three or more wells via the inlet tube, the tubing, the transwell tubes, and the outlet tube;
wherein the wells comprising the gastrointestinal tissue and/or cells, the liver tissue and/or cells, and the kidney tissue and/or cells comprise the tubing comprising gaps of dialysis membrane; and
wherein at least one of the wells comprises an outer shell, an insert, and a fluid space disposed therebetween, the outer shell being a solid piece and defining the shape of the well and the insert comprising a semipermeable wall defining an interior of the well, that allows for diffusion of chemicals, gasses, and fluids between the fluid space and the interior of the well, wherein the fluid space is in fluid communication with the inlet and outlet tubes.
