Microfluidic system and methods of use

• US 6,900,021 B1
• Filed: 05/18/1998
• Issued: 05/31/2005
• Est. Priority Date: 05/16/1997
• Status: Expired due to Fees

• Current Assignee: Alberta Research Council, University of Alberta
• Original Assignee: University of Alberta
• Inventors: Andersson, Per, Smith, Richard, Salimi-Moosavi, Hossein, Szarka, Roderick, Li, Paul C. H., Harrison, Daniel Jed
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/080,546
• Time in Patent Office: 2,570 Days
• Field of Search: 137/806, 436/52, 436/63, 436/518, 436/164, 436/514, 422/81, 422/101, 422/68.1, 422/73, 424/278.1, 435/32, 435/309.1, 435/286.1, 435/288, 435/7.24, 435/7.21, 435/288.2, 435/288.5, 280/461
• US Class Current: 435/7.21
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: B81B 1/00 Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream

Abstract

This invention relates to a novel microfluidic device and methods of using this device to conduct in vitro studies on the reaction and effects of various compounds on cells. More particularly, it relates to a method for using stop flow in a microfluidic system to study the effect of compounds on individual cells. It also provides a method for observing the effects of candidate compounds on leukocyte rolling.

Claims

1. A method of observing the effect of one or more candidate compounds on cells in a microfluidic device comprising:

(a) providing a microfluidic device comprising a main flow path, an outlet, at least two inlet flow paths and a detection zone, wherein at least one inlet flow path intersects and merges with the main flow path at the detection zone;

(b) applying at least one cell which is capable of flowing in the microfluidic device to a first of the at least two inlet flow paths and a candidate compound to a second of the at least two inlet flow paths;

(c) inducing flow of the at least one cell and the candidate compound toward the detection zone without mixing;

(d) stopping the flow of the at least one cell and the candidate compound when the at least one cell and the candidate compound are in the detection zone;

(e) allowing the at least one cell to mix with the candidate compound in the detection zone; and

(f) observing the effect of the candidate compound on the at least one cell in the detection zone at the time at least one cell mixes with the candidate compound in the detection zone.

2. The method of claim 1 wherein the candidate compound being studied is an inhibitor, and the cells are lymphocytes.

3. The method of claim 1 wherein the flow paths are coated with a substance selected from the group consisting of proteins, glycoproteins, phospholipids, hydrophilic polymers and hydrophobic polymers.

4. The method of claim 3 wherein the flow path is coated with protein.

5. The method of claim 3 wherein the flow is induced by an electric force.

6. The method of claim 4 wherein the flow is induced by positive or negative fluid pressure.

7. A method of observing the effect of a candidate compound on a cell, the method comprising:

delivering a cell to a first flow path in a microfluidic device;

delivering a candidate compound to a second flow path in a microfluidic device;

inducing flow of the cell and the candidate compound toward a detection zone in the microfluidic device;

stopping the flow of the cell and the candidate compound at a detection zone in the microfluidic device;

mixing the cell and the candidate compound at the detection zone; and

observing an effect of the candidate compound on the cell in the detection zone at the moment the cell mixes with the candidate compound.