High throughput screening assay systems in microscale fluidic devices

• US 6,558,960 B1
• Filed: 11/21/2000
• Issued: 05/06/2003
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Caliper Holdings Incorporated
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Parce, J. Wallace, Kopf-Sill, Anne R., Bousse, Luc J.
• Primary Examiner(s): Ponnaluri, Padmashri
• Assistant Examiner(s): TRAN, MY CHAU T
• Application Number:
  US09/718,235
• Time in Patent Office: 896 Days
• Field of Search: 422/55, 422/57, 422/58, 422/82.01, 435/6, 435/7.9, 435/7.1, 435/287.1, 435/176, 435/287.2, 435/288.3, 435/288.4, 435/288.7, 436/519, 436/518, 436/527, 436/531, 436/149, 436/150, 436/151, 436/164, 436/165, 436/172, 204/400, 204/403, 204/409, 204/412
• US Class Current: 436/519
• 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: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01J 2219/00961 Temperature
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• 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 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 : electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/5008 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 : for testing antineoplastic activity
• CPC Class Codes: G01N 33/502 : for testing non-proliferative effects
• CPC Class Codes: G01N 33/5064 : Endothelial cells
• CPC Class Codes: G01N 33/5091 : for testing the pathological state of an organism
• CPC Class Codes: G01N 33/5097 : involving plant cells immunoassays of plant cells G01N33/56961
• CPC Class Codes: G01N 33/5304 : Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/57415 : of breast
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10S 366/02 : Micromixers: segmented laminar flow with boundary mixing orthogonal to the direction of fluid propagation with or without geometry influences from the pathway
• CPC Class Codes: Y10S 435/81 : Packaged device or kit
• CPC Class Codes: Y10S 435/817 : Enzyme or microbe electrode
• CPC Class Codes: Y10S 436/804 : Radioisotope, e.g. radioimmunoassay
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 : Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Claims

1. A method of screening a plurality of test compounds for an effect on a biochemical system, comprising:

providing a first channel and a second channel which intersect;

continuously flowing beads carrying interacting components of the biochemical system into said first channel;

introducing at least a first bead comprising a first test compound into the first channel from the second channel;

controllably releasing said at least first test compound and said interacting components of the biochemical system from said respective beads;

detecting an effect of the first test compound on an interaction between the continuously flowing components of the biochemical system.

2. The method of claim 1, further comprising providing a detection zone in said first or said second channel.

3. The method of claim 1, wherein the interacting components comprise a component of a receptor/ligand binding pair.

4. The method of claim 1, wherein the components are selected from an enzyme, an enzyme substrate, and a biological cell.

5. The method of claim 1, wherein the effect of the first test compound on the biochemical system comprises the production of a fluorescent signal.

6. The method of claim 1, further comprising introducing a plurality of beads into the first channel from the second channel wherein each of said plurality of beads comprises a single test compound.

7. The method of claim 1, wherein the components comprise a biological cell and the method further comprises the step of detecting the effect of the first test compound on the cell.

8. The method of claim 1, wherein the components comprises an enzyme and an enzyme substrate and the method further comprises detecting the formation of a enzyme-substrate product.

9. The method of claim 1, wherein the components comprise a receptor and a ligand and the method further comprises detecting the binding of the ligand to the receptor.

10. The method of claim 1, wherein the step of controllably releasing comprises exposing the beads to a releasing agent.

11. The method of claim 10, wherein the releasing agent is selected from a group consisting of light, acid and base.

12. The method of claim 1, wherein the step of continuously flowing comprises flowing said beads electroosmotically.

13. The method of claim 1, wherein an electrokinetic fluid direction system is used for flowing said beads carrying interacting components of the biochemical system and the plurality of test compounds.

14. The method of claim 1, wherein the components produce a detectable signal representative of a function of the biological system.