# US 2012/0083425 A1 · High-Throughput Platform Comprising Microtissues Perfused With Living Microvessels

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- Number: US 2012/0083425 A1
- Document ID: US20120083425A1
- Status: Published application
- Kind: A1
- Application number: 13/253,820
- Filed: 2011-10-05
- Published: 2012-04-05
- Earliest claimed: 2010-10-05
- Assignees: The Regents of the University of California
- Inventors: Steven C. George; Christopher C.W. Hughes; Abraham P. Lee; Monica Moya; Yu-Hsiang Hsu
- Web page: https://patentgrep.com/patent/US20120083425A1

## CPC

- G01N 33/5082: {Supracellular entities, e.g. tissue, organisms}
- C12N 5/0062: {General methods for three-dimensional culture}
- C12N 5/0691: {Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5011: {for testing antineoplastic activity}
- C12N 2533/30: Synthetic polymers
- C12N 2535/00: Supports or coatings for cell culture characterised by topography
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided is a process for creating a 3D metabolically active microtissue perfused with living microvessels which have a direct fluidic connection with neighboring microfluidic channels. The process comprises preparing a template comprising a plurality of channels, and creating a network within said channels, said network comprising microfluidic channels, metabolically active living microvessels, and microtissues. The microvessels can sprout from said microvessels and/or form within the microtissue in response to a stimulus applied from said microfluidic channels or stimulus derived from the said tissues. In another embodiment, a device is provided comprising a supportive structure, one or more microfluidic channels, one or more microtissue compartments, and one or more microvessels, whereby the microvessels connect said microfludic channels and microtissue and perfuse the microtissue to deliver fluid from the microfluidic channels to the microtissues.

## Claims

### Claim 1

A process for creating a 3D metabolically active network of living microvessels, comprising
preparing a template comprising a plurality of microfluidic and microtissue channels, and providing a stimulus to said microfluidic channels, whereby the stimulus creates a 3D metabolically active network of living microvessels.

### Claim 2 (depends on 1)

The process of claim 1, wherein the microvessels connect the microfluidic and microtissue channels and deliver fluid between said channels.

### Claim 3 (depends on 1)

The process of claim 1, wherein the microvessels are formed within the microtissue.

### Claim 4 (depends on 1)

The process of claim 1, wherein the microvessels provide nutrition and remove waste from the microtissue.

### Claim 5 (depends on 1)

The process of claim 1, wherein the microvessels are not microfabricated.

### Claim 6 (depends on 1)

The process of claim 1, wherein the stimulus is provided by cells within the microfluidic channels themselves, or by cells within said microtissues.

### Claim 7 (depends on 1)

The process of claim 1, wherein the stimulus is selected from a group consisting of oxygen concentration, carbon dioxide concentration, concentration of growth factors and other nutrients, flow rate of fluid, pressure, cellular concentration, temperature, dimensions of channels and connecting ports, and composition of the extracellular matrix.

### Claim 8 (depends on 1)

The process of claim 1, wherein the microfluidic and microtissue channels comprise normal or diseased/abnormal cells.

### Claim 9 (depends on 8)

The process of claim 8, wherein the said cells are selected from a group consisting of stem, endothelial, stromal, epithelial, neuronal, connective, myocardial, hepato, renal, tumor heart, liver, pancreas, muscle, brain, and kidney cells.

### Claim 10 (depends on 8)

The process of claim 8, wherein the cells are human cells.

### Claim 11 (depends on 8)

The process of claim 8, wherein the diseased cell is a cancer cell.

### Claim 12 (depends on 8)

The process of claim 8, wherein the cells are obtained from a specific human individual.

### Claim 13 (depends on 1)

The process of claim 1, wherein the microfludic channels comprise endothelial cells, and said endothelial cells migrate into the microtissue to form said microvessels.

### Claim 14 (depends on 1)

The process of claim 1, wherein the microtissue chamber comprises endothelial and/or stromal cells chamber and the microvessels are derived from said endothelial cells.

### Claim 15

An article comprising
a supportive structure, one or more microfluidic channels, one or more microtissue compartments, and one or more microvessels, wherein the microvessels connect said microfludic channels and microtissue and perfuse said microtissue, thereby allowing delivery of fluid or nutrients from the microfluidic channels to the microtissues.

### Claim 16 (depends on 15)

The article of claim 15, wherein the microvessels are metabolically active or living.

### Claim 17 (depends on 15)

The article of claim 15, wherein the microfluidic channels, microtissues or the combination thereof, is seeded with cells obtained from an individual.

### Claim 18

A method of identifying a candidate drug or treatment regime comprising
adding a test compound/drug into a microfluidic channel within a microfluidic device, wherein the microfluidic device comprises one or more microfluidic channels, one or more microtissue compartments, and one or more microvessels,
and monitoring for beneficial changes, appropriate for the drug type being identified, in either the microvessels, or microtissue, or a combination thereof; or the compound's kinetics.

### Claim 19 (depends on 18)

The method of claim 18, wherein the compound is selected from a group consisting of cancer drug, cell proliferation drug, and wound healing/repair drug.

### Claim 20 (depends on 18)

The method of claim 18, wherein the microfluidic channels, microtissue or the combination thereof, is seeded with cells obtained from an individual