# US 2018/0024110 A1 · Fluidic device for quantifying the dynamic permeability and hydraulic conductivitiy of living tissue layers

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- Number: US 2018/0024110 A1
- Document ID: US20180024110A1
- Status: Published application
- Kind: A1
- Application number: 15/694,577
- Filed: 2017-09-01
- Published: 2018-01-25
- Earliest claimed: 2015-03-04
- Assignees: President and Fellows of Harvard College
- Applicants: President and Fellows of Harvard College
- Inventors: Daniel Levner; Christopher David Hinojosa; Andries D. van der Meer; Marinke van der Helm; Abhishek Jain; Donald Elliot Ingber; Marjon Zamani
- Web page: https://patentgrep.com/patent/US20180024110A1

## CPC

- G01N 33/4833: {of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735)}
- 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 3/502746: {characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves}
- G01N 15/0826: {and measuring fluid flow rate, i.e. permeation rate or pressure change}
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- B01L 2300/0654: Lenses; Optical fibres
- B01L 2300/0877: Flow chambers
- B01L 2300/0883: Serpentine channels
- B01L 2400/0457: passive flow or gravitation
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/082: Active control of flow resistance, e.g. flow controllers
- B01L 2400/084: Passive control of flow resistance
- B01L 2400/086: using baffles or other fixed flow obstructions
- G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05)
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.

## Claims

### Claim 1

A system for measuring hydraulic conductivity associated with a cell layer, the system comprising:
a microfluidic device having a first microchannel, a second microchannel, and a barrier located at an interface region between the first microchannel and the second microchannel, the barrier including a first side facing toward the first microchannel and a second side facing toward the second microchannel, the first side having the cell layer adhered thereto, the first and second microchannel comprising an input and output;
a working-fluid reservoir having a working fluid that is fluidically coupled to the input of the first microchannel;
a first output line for delivering a first portion of a working fluid from the first microchannel to a first output-fluid reservoir;
a fluid-resistance element coupled to the first output line, the fluid-resistance element having a first fluidic resistance that causes a pressure drop across the fluid-resistance element; and
a second output line for delivering a second portion of the working fluid from the second microchannel to a second output-fluid reservoir,
wherein migration of the second portion of the working fluid from the first microchannel to the second microchannel through the cell layer is indicative of the hydraulic conductivity associated with the cells.

### Claim 2 (depends on 1)

The system of claim 1, wherein the fluid-resistance element can be adjusted or altered.

### Claim 3 (depends on 1)

The system of claim 1, wherein the working-fluid reservoir is positioned above the first microchannel for delivering the fluid to the first microchannel under a force of gravity.

### Claim 4 (depends on 1)

The system of claim 1, wherein working-fluid reservoir is coupled to a pump for delivering the fluid to the first microchannel under a force of pressure.

### Claim 5 (depends on 1)

The system of claim 1, further including an image-gathering device for gathering images of the fluid migrating through the cell layer and the barrier.

### Claim 6

A system for measuring hydraulic conductivity associated with cells, comprising:
a microfluidic device having a first microchannel, a second microchannel, and a barrier located at an interface region between the first microchannel and the second microchannel, the barrier including a first side facing toward the first microchannel and a second side facing toward the second microchannel, at least one of the first side and the second side having a cell layer adhered thereto;
a first fluid path associated with the first microchannel for delivering a fluid to and from the first microchannel; and
a second fluid path associated with the second microchannel for delivering, from the second microchannel, the fluid that has migrated through the barrier and the cell layer;
wherein a flow rate of the fluid that is delivered from the second microchannel is indicative of the hydraulic conductivity associated with the cell layer.

### Claim 7 (depends on 6)

The system of claim 6, wherein the first fluid path comprises a fluid-resistance element downstream from the first microchannel to maintain a substantially constant fluid pressure along the cell layer adhered to the barrier.

### Claim 8 (depends on 7)

The system of claim 7, wherein the fluid-resistance element can be adjusted or altered.

### Claim 9 (depends on 1)

The system of claim 1, further comprising a fluid reservoir fluidically coupled to said first microchannel.

### Claim 10 (depends on 9)

The system of claim 9, wherein the fluid reservoir is positioned above the first microchannel for delivering the fluid to the first microchannel under a force of gravity.

### Claim 11 (depends on 9)

The system of claim 9, wherein fluid reservoir is coupled to a pump for delivering the fluid to the first microchannel under a force of pressure.

### Claim 12 (depends on 6)

The system of claim 6, further including an image-gathering device for gathering images of the fluid migrating through the cell layer and the barrier.
