Radial microfluidic devices and methods of use

• US 10,202,569 B2
• Filed: 07/22/2016
• Issued: 02/12/2019
• Est. Priority Date: 07/24/2015
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Novak, Richard, Conegliano, David, Teixeira, Liliana, Ingber, Donald E.
• Primary Examiner(s): Ware, Deborah K
• Application Number:
  US15/217,714
• Publication Number:
  US 20170022464A1
• Time in Patent Office: 935 Days
• CPC Class Codes: B01L 2200/0694 Creating chemical gradients in a fluid
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025

Abstract

A microfluidic device for simulating a function or response of a tissue is disclosed. The device includes an inlet for receiving a fluid in the device, and an outlet for removing the fluid from the device. The device further includes a fluid channel in fluid communication with the inlet and the outlet for flowing the fluid through the device. The fluid channel defines a chamber well that receives cells associated with the tissue. The device also includes an interface structure between the fluid channel and the chamber well for permitting migration of at least one of cells, particulates, chemicals, molecules, liquids, or gases between the fluid within the fluid channel and the chamber well.

Claims

1. A method of culturing cells, comprising:

1) providing a) microfluidic device comprising i) a chamber, said chamber comprising geometric features and a lumen, said lumen covered by ii) a removable lid and in fluidic communication with iii) one or more fluidic channels, b) material capable of forming a gel, and c) cells;

2) removing said removable lid;

3) introducing said material under conditions such that a gel forms in said lumen, said gel confined by one or more of said geometric features, and

4) introducing said cells to said gel, said cells in contact with fluid from said one or more fluidic channels.

2. The method of claim 1, wherein said gel comprises collagen.

3. The method of claim 1, wherein said chamber comprises a round well.

4. The method of claim 1, wherein said geometric features comprise posts.

5. The method of claim 4, wherein said posts comprise a concentric array of posts.

6. The method of claim 1, wherein said cells are cord blood cells.

7. The method of claim 1, wherein

the gel comprises a first gel confined by at least one of the one or more fluidic channels, said cells comprising first cells within the first gel, the method further comprising:

providing a second gel comprising second cells in the at least one of the one or more fluidic channels; and

detecting migration of said first cells toward said second cells.

8. The method of claim 7, wherein said first cells are cord blood cells.

9. The method of claim 7, wherein said second cells are endothelial cells.

10. The method of claim 9, wherein said endothelial cells are human umbilical vein endothelial cells.

11. The method of claim 7, wherein said geometric features comprise posts.

12. The method of claim 11, wherein said posts comprise a concentric array of posts.