# US 7,364,905 B2 · Apparatus and method for high throughput analysis of compound-membrane interactions

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- Number: US 7,364,905 B2
- Document ID: US7364905B2
- Status: Granted
- Kind: B2
- Application number: 10/139,766
- Filed: 2002-05-06
- Published: 2003-10-23
- Granted: 2008-04-29
- Earliest claimed: 2001-11-29
- Assignees: TechElan, LLC
- Inventors: Ilya Feygin; Rafail Kushak
- Web page: https://patentgrep.com/patent/US7364905B2

## CPC

- B01J 19/0046: {Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays (synthesis methods per se C40B50/00)}
- C40B 60/12: for screening libraries
- B01J 2219/00286: Reactor vessels with top and bottom openings
- B01J 2219/00423: using filtration, e.g. through porous frits
- B01J 2219/00585: Parallel processes
- B01J 2219/00599: Solution-phase processes
- B01J 2219/00756: Compositions, e.g. coatings, crystals, formulations
- Y10T 436/10: Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

An article and method for high throughput and a high content investigation of compound interactions with live tissue or its substitutes under controlled conditions during compound absorption and related processes. In some variations of the illustrative embodiment, the article is a multi-chamber enclosure having at least two chambers separated by a membrane. Membranes can be prepared from live epithelial tissue or from an artificial material with or without attached cells from cell-line cultures. Each chamber is advantageously connected to a fluidic-control system by tubes that pass through a feed fitting. In addition to coupling the chambers with the fluidic-control system, the feed fitting, which is spring-biased, provides a sealing force to seal the enclosure. In some variations, one or more multi-chamber enclosures are installed in a mother chamber, which provides controlled environmental conditions. Operation of the article includes automatic introduction of compounds, buffers, and gases into the chambers, establishing reaction conditions inside the chambers, and individually sampling from the chambers.

## Claims

### Claim 1

An article comprising:
an enclosure defining a sealable volume that receives fluid, wherein said enclosure has a first aperture and a second aperture;
a membrane. wherein said membrane is disposed in the enclosure, and further wherein said membrane segregates the volume defined by the enclosure into a first chamber and a second chamber;
a first feed fitting, wherein said first feed fitting is received by said first aperture;
a first spring-biasing element, wherein said first spring-biasing element mechanically couples to said first feed fitting;
a second feed fitting, wherein said second feed fitting is received by said second aperture; and
a second spring-biasing element, wherein said second spring-biasing element mechanically couples to said second feed fitting; wherein:
said first spring-biasing element, said first feed fitting, said first aperture, said second aperture, said second feed fitting and said second spring-biasing element are aligned along a first axis.

### Claim 2 (depends on 1)

The article of claim 1 wherein:
said first spring-biasing element exerts a first force;
said second spring-biasing element exerts a second force; and
said first force and said second force collectively place said enclosure in compression.

### Claim 3 (depends on 1)

The article of claim 1 wherein said enclosure comprises a first housing and a second housing, wherein said first and second housing are coupled to one another.

### Claim 4 (depends on 3)

The article of claim 3 wherein:
said first housing has a first end and a second end;
said first housing is relatively larger at said second end and relatively smaller at said first end;
said second housing has a first end and a second end;
said second housing is relatively larger at said second end and relatively smaller at said first end; and
said first housing and said second housing engage one another at said relatively larger second ends.

### Claim 5 (depends on 4)

The article of claim 4 wherein:
said first aperture is disposed at said first end of said first housing; and
said second aperture is disposed at said first end of said second housing.

### Claim 6 (depends on 5)

The article of claim 5 wherein:
said second end of said first housing is substantially open thereby defining a relatively large aperture compared to said first aperture at said first end of said first housing; and
said second end of said second housing is substantially open thereby defining a relatively large aperture compared to said second aperture at said first end of said second housing.

### Claim 7 (depends on 4)

The article of claim 4 wherein each of said first housing and said second housing have a conical shape.

### Claim 8 (depends on 6)

The article of claim 6 wherein:
said membrane is disposed between said first housing and said second housing proximal to said relatively large aperture of each of said first housing and said second housing; and
said first chamber is defined within said first housing and said second chamber is defined within said second housing.

### Claim 9 (depends on 8)

The article of claim 8 wherein said membrane is selected from the group consisting of live tissue, synthetic tissue and synthetic tissue with cells attached.

### Claim 10 (depends on 8)

The article of claim 8 wherein:
said first feed fitting has a first end and a second end;
said first spring-biasing element couples to said first end of said first feed fitting;
said second end of said first feed fitting has a first opening; and
said second end of said first feed fitting is received by said first aperture of said enclosure so that said first opening communicates with said first chamber.

### Claim 11 (depends on 10)

The article of claim 10 further comprising a tube, wherein said tube extends into said first chamber through said first opening of said first feed fitting.

### Claim 12 (depends on 11)

The article of claim 11 further comprising a fluid control system, wherein:
said fluid control system is coupled to said tube;
said fluid control system supplies fluid to and receives fluid from said first chamber;
and said fluid control system is coupled to analytical devices.

### Claim 13 (depends on 1)

The article of claim 1, further comprising a frame, wherein:
said frame has two spaced-apart rails;
said first spring-biasing element is coupled to one of said spaced-apart rails; and
said second spring-biasing element is coupled to the other of said spaced-apart rails.

### Claim 14

An article comprising:
a first housing and a second housing, wherein said first housing and said second housing are coupled to one another, wherein:
said first housing has a first interior volume, a small aperture, and a large aperture;
said second housing has a second interior volume, a small aperture, and a large aperture; and
said first housing and said second housing are coupled proximal to said large apertures;
a first feed fitting, wherein said first feed fitting has an opening and said first feed fitting is received by said small aperture of said first housing;
a first plurality of tubes, wherein said first plurality of tubes pass through said opening in said first feed fitting and extend into said first interior volume of said first housing;
a second feed fitting, wherein said second feed fitting has an opening and said second feed fitting is received by said small aperture of said second housing;
a second plurality of tubes, wherein said second plurality of tubes pass through said opening in said second feed fitting and extend into said second interior volume of said second housing;
a first spring-biasing element that mechanically couples to said first feed fitting; and
a second spring-biasing element that mechanically couples to said second feed fitting.

### Claim 15 (depends on 14)

The article of claim 14 further comprising a membrane, wherein:
said membrane is disposed between said first housing and said second housing;
said membrane and said first housing define a first chamber that comprises said first interior volume;
said membrane and said second housing define a second chamber that comprises said second interior volume; and
said membrane forms a seal between said first chamber and said second chamber.

### Claim 16 (depends on 15)

The article of claim 15 further comprising:
a first vent, wherein said first vent is disposed in said first housing and vents said first chamber;
a second vent, wherein said second vent is disposed in said second housing vents said second chamber.

### Claim 17 (depends on 15)

The article of claim 15 further comprising an electrode, wherein said electrode passes through said opening in said first feed fitting and extends into said first chamber.

### Claim 18 (depends on 15)

The article of claim 15 further comprising a fluid control system, wherein:
said first plurality of tubes and said second plurality of tubes are coupled to said fluid control system;
said fluid control system supplies fluid to at least one of said first and second chambers;
said fluid control system receives fluid from at least one of said first and second chambers; and
said fluid control system is coupled to analysis devices and control devices.

### Claim 19 (depends on 14)

The article of claim 14 further comprising a device for fixing each tube of said first plurality of tubes in a desired location and orientation within said first chamber.

### Claim 20 (depends on 14)

The article of claim 14 further comprising a third housing, wherein:
said third housing has an interior volume; and
said third housing is flanked by and couples to said first housing and said second housing.

### Claim 21 (depends on 20)

The article of claim 20 further comprising a first membrane and a second membrane, wherein:
said first membrane is disposed between said first housing and said third housing;
said first membrane and said first housing define a first chamber that comprises said first interior volume;
said second membrane is disposed between said second housing and said third housing;
said second membrane and said second housing define a second chamber that comprises said second interior volume;
said third housing, said first membrane, and said second membrane define a third chamber that comprises said third interior volume; and wherein:
said first membrane forms a seal between said first chamber and said third chamber; and
said second membrane forms a seal between said second chamber and said third chamber.

### Claim 22 (depends on 15)

The article of claim 15 wherein said first housing, said second housing and said membrane collectively compose a first multi-chamber enclosure, and further comprising:
a second multi-chamber enclosure; and
a frame;
wherein said first multi-chamber enclosure and said second multi-chamber enclosure are mechanically coupled to said frame.

### Claim 23 (depends on 22)

The article of claim 22 wherein:
said frame comprises a first rail and a second rail;
said first spring-biasing element is mechanically coupled to said first rail; and
said second spring-biasing element is mechanically coupled to said second rail.

### Claim 24 (depends on 22)

The article of claim 22 further comprising a mother chamber, wherein said mother chamber receives said frame having said first multi-chamber enclosure and said second multi-chamber enclosure.