Rheologically biomimetic fluid surrogate

Patent metadata

Field	Value
Publication number	US-11788044-B2
Application number	US-202016820530-A
Country	US
Kind code	B2
Filing date	Mar 16, 2020
Priority date	Sep 21, 2017
Publication date	Oct 17, 2023
Grant date	Oct 17, 2023

Abstract

The present invention contemplates compositions, devices and methods of simulating biological fluids in a fluidic device, including but not limited to a microfluidic chip. In one embodiment, fluid comprising a colloid under flow in a microfluidic chip has a fluid density or viscosity similar to a bodily fluid, e.g. blood, lymph, lung fluid, or the like. In one embodiment, a fluid is provided as a Theologically biomimetic blood surrogate or substitute for simulating physiological shear stress and cell dynamics in fluidic device, including but not limited to immune cells.

First claim

The invention claimed is:

1. A method, comprising:
a) providing i) a microfluidic device comprising a body comprising a microchannel therein, said microchannel comprising (1) a membrane disposed within at least a portion of the microchannel and configured to separate the microchannel into first and second microchannels, and (2) endothelial cells in a layer on said membrane in said first microchannel; and ii) a fluid, said fluid comprising a colloid density-modifying reagent and one or more immune cell types; and b) flowing said fluid into said first microchannel to produce a shear rate and an increased number of said immune cells that are adhered to said endothelial cells on said membrane in said microchannel in the presence of the colloid density-modifying reagent compared to in the absence of the colloid density-modifying reagent in said first microchannel.

2. The method of claim 1 , wherein said flowing produces an interaction by said one or more immune cell types with said endothelial cells in said first microchannel without the use of gravity.

3. The method of claim 1 , wherein the membrane is coated with at least one attachment molecule that supports adhesion of a plurality of living cells.

4. The method of claim 1 , wherein the membrane is a porous membrane.

5. The method of claim 1 , wherein the membrane is at least partially flexible.

6. The method of claim 1 , wherein the endothelial cells are on the bottom of the membrane.

7. The method of claim 6 , wherein epithelial cells are on the top of the membrane.

8. The method of claim 1 , wherein said colloid is a silica-based colloid.

9. The method of claim 1 , wherein the method further comprises, prior to step b), exposing said endothelial cells to an inflammatory cytokine.

10. The method of claim 1 , wherein said endothelial cells are from a healthy human patient.

11. The method of claim 1 , wherein said endothelial cells are from a human patient with symptoms of an inflammatory or autoimmune disorder.

Assignees

• Emulate Inc

Inventors

• Varone Antonio
• Kasendra Magdalena
• Lucchesi Carolina
• Kerns S Jordan
• Barrile Riccardo
• Barthakur Sonalee

Classifications

• C12M23/16 Primary

  Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title

• B01L3/502715

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• B01L3/502761 Primary

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• C12M23/26

  flexible (flexible containers for laboratory use B01L3/505) · CPC title

• C12M25/02

  Membranes; Filters (filters or filtration in general B01D24/00-B01D41/00) · CPC title