# US 10,870,823 B2 · Biomimetic device

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- Number: US 10,870,823 B2
- Document ID: US10870823B2
- Status: Granted
- Kind: B2
- Application number: 14/737,809
- Filed: 2015-06-12
- Published: 2015-12-17
- Granted: 2020-12-22
- Earliest claimed: 2014-06-12
- Assignees: Lehigh University
- Applicants: Lehigh University
- Inventors: Yaling Liu; Antony Thomas
- Web page: https://patentgrep.com/patent/US10870823B2

## CPC

- C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)}
- C12M 23/20: {Material Coatings (immunocoatings C12M25/00)}
- C12M 25/02: {Membranes; Filters (filters or filtration in general B01D24/00-B01D41/00)}
- 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

Described herein are apparatus comprising: a first layer comprising a first microfluidic channel; a second layer comprising a second microfluidic channel; and a membrane for culturing cells; along with methods of making and using same.

## Claims

### Claim 1

An electrode-free apparatus comprising:
a first layer formed of polydimethylsiloxane, the first layer comprising a first microfluidic channel having a first length and a first width, the first width being uniform along the first length of the first microfluidic channel;
a second layer formed of polydimethylsiloxane, the second layer comprising a second microfluidic channel having a second length and a second width, the second width being uniform along the second length of the second microfluidic channel, the second width being at least twice as wide as the first width;
a membrane for culturing cells, the membrane having a length that is at least the same as either the first or second length and a width that is at least the same as either the first or second width, and the membrane having a first major surface and a second major surface; and
wherein the membrane is bonded to each of the first layer and the second layer by a polydimethylsiloxane mortar film having a thickness ranging from about 2 microns to about 3 microns, and wherein the membrane is configured to have a layer of first cells disposed on the first major surface of the membrane facing the first microfluidic channel or a layer of first cells disposed on the second major surface of the membrane facing the second microfluidic channel.

### Claim 2 (depends on 1)

The apparatus according to claim 1, wherein a portion of the membrane for culturing cells is semi-permeable and is positioned between the first layer and the second layer.

### Claim 3 (depends on 1)

The apparatus according to claim 1, wherein the first layer and second layer comprise the same material.

### Claim 4 (depends on 1)

The apparatus according to claim 1, wherein the membrane for culturing cells comprises a material selected from a polycarbonate, a polyester, polyethylene terephthalate, a mixed cellulose ester, PDMS and a combination of two or more thereof.

### Claim 5 (depends on 1)

The apparatus according to claim 1, wherein the membrane for culturing cells is in fluid communication with one or both of the first and second layers.

### Claim 6 (depends on 1)

The apparatus according to claim 1, wherein the first layer and the second layer are in an offset arrangement and the offset arrangement creates a plurality of sections.

### Claim 7 (depends on 1)

The apparatus according to claim 1, wherein the first layer and the second layer are in a parallel arrangement.

### Claim 8 (depends on 1)

The apparatus according to claim 1, wherein the membrane for culturing cells is coupled to the first layer.

### Claim 9 (depends on 1)

The apparatus according to claim 1, wherein the membrane for culturing cells is adapted to culture a plurality of cell lines.

### Claim 10 (depends on 1)

The apparatus according to claim 1, wherein the first cells are endothelial cells or tumor cells.

### Claim 11 (depends on 1)

The apparatus according to claim 1, further comprising a layer of second cells disposed on a surface of the membrane facing the second microfluidic channel.

### Claim 12 (depends on 11)

The apparatus according to claim 11, wherein the first cells are endothelial cells and the second cells are smooth muscle cells or tumor cells.

### Claim 13 (depends on 1)

The apparatus according to claim 1, wherein the first width is 350 microns and the second width is 1,000 microns.

### Claim 14 (depends on 1)

The apparatus according to claim 1, further comprising a treatment agent provided in one of the first and second microfluidic channels.

### Claim 15 (depends on 14)

The apparatus according to claim 14, wherein the treatment agent is tumor necrosis factor-alpha (TNT-a).

### Claim 16 (depends on 1)

The apparatus according to claim 1, further comprising a tracer molecule provided in one of the first and second microfluidic channels.

### Claim 17 (depends on 16)

The apparatus according to claim 16, wherein the tracer molecule is one or a combination of fluorescent FITC sodium salt and FITC-Dextran.

### Claim 18

An electrode-free apparatus comprising:
a first layer comprising a first microfluidic channel forming a first flow direction, the first microfluidic channel having a first height of about 100 microns a first width of about 350 microns as measured perpendicular to the first flow direction;
a second layer comprising a second microfluidic channel forming a second flow direction, the second microfluidic channel having a second height of about 100 microns and a second width of about 1,000 microns as measured perpendicular to the second flow direction;
a membrane for culturing cells, the membrane having a first major surface and a second major surface, the membrane comprising pores extending between the first and second major surfaces, whereby the membrane has an average pore density of about 1.5×107 pores/cm2; and
a layer of first cells disposed on the first major surface of the membrane facing the first microfluidic channel or a layer of first cells disposed on the second major surface of the membrane facing the second microfluidic channel;
wherein the first microfluidic channel overlaps the second microfluidic channel at an intersection point, and at the intersection point the first flow direction is perpendicular to the second flow direction.

### Claim 19

An electrode-free apparatus comprising:
a first layer formed of polydimethylsiloxane, the first layer comprising a first microfluidic channel having a first height of about 100 microns, a first length, and a first width of about 350 microns, the first width being uniform along the first length of the first microfluidic channel;
a second layer formed of polydimethylsiloxane, the second layer comprising a second microfluidic channel having a second height of about 100 microns, a second length, and a second width of about 1,000 microns, the second width being uniform along the second length of the second microfluidic channel, the second width being wider than the first width;
a membrane for culturing cells, the membrane having a length that is at least the same as either the first or second length and a width that is at least the same as either the first or second width, and the membrane having a first major surface and a second major surface, the membrane comprising pores extending between the first and second major surfaces, whereby the membrane has an average pore density of about 1.5×107 pores/cm2; and
wherein the membrane is bonded to each of the first layer and the second layer by a polydimethylsiloxane mortar film having a thickness ranging from about 2 microns to about 3 microns, and wherein the membrane is configured to have a layer of first cells disposed on the first major surface of the membrane facing the first microfluidic channel or a layer of first cells disposed on the second major surface of the membrane facing the second microfluidic channel.
