High throughput screening assay systems in microscale fluidic devices

• US 6,399,389 B1
• Filed: 07/07/2000
• Issued: 06/04/2002
• 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): Chin, Christopher L.
• Application Number:
  US09/612,587
• Time in Patent Office: 697 Days
• Field of Search: 422/63, 422/65, 422/66, 422/81, 422/81.01, 422/81.02, 422/82.05, 422/100, 422/101, 422/104, 436/43, 436/44, 436/149, 436/174, 436/150, 436/47, 204/457
• US Class Current: 436/47
• 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

A method for screening a plurality of compounds is used in conjunction with microfluidic devices for performing high throughput screening assays. A conveyor system is used to transport and dispense libraries of compounds into one or more sample port of a microfluidic device. The microfluidic device accesses the compounds in order to screen large numbers of different compounds for their effects on a variety of chemical and biochemical systems.

Claims

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

providing a body structure comprising at least one microchannel, a pipettor extending from said body structure, wherein said pipettor is in fluid communication with said at least one microchannel;

flowing at least one component of a biochemical system through said at least one microchannel;

periodically introducing a test compound to contact said component of said biochemical system by transferring said test compound through the pipettor into said at least one microchannel; and

detecting an effect of said test compound on said at least one component of said biochemical system.

2. The method of claim 1, wherein the periodically introducing step comprises drawing said test compound from a multiwell plate and into said pipettor.

3. The method of claim 1, wherein said component of said biochemical system produces a detectable signal representative of a function of said biochemical system.

4. The method of claim 1, wherein said body structure comprises at least two intersecting microchannels.

5. The method of claim 1, wherein said biochemical system comprises a receptor/ligand binding pair, wherein at least one of said receptor or ligand has a detectable signal associated therewith.

6. The method of claim 5, wherein said receptor and said ligand flow along said first channel at different rates.

7. The method of claim 1, wherein said biochemical system comprises a receptor/ligand binding pair, wherein binding of said receptor to said ligand produces a detectable signal.

8. The method of claim 1, wherein said biochemical system comprises cells, and said detecting step comprises determining an effect of said test compound on said cells.

9. The method of claim 8, wherein said cells are capable of producing a detectable signal corresponding to a cellular function, and said detecting step comprises detecting an effect of said test compound on said cells.

10. The method of claim 1, wherein said biochemical system comprises an enzyme and a substrate for said enzyme, wherein action of said enzyme on said substrate produces a detectable signal.

11. The method of claim 1, wherein said pipettor is an electropipettor.

12. The method of claim 11, wherein transferring a test compound into and through said electropipettor comprises electroosmotically drawing and moving said test compound into and through said electropipettor.

13. The method of claim 1, wherein said transferring a test compound into and through said pipettor comprises sampling a spacer compound before and after sampling of said test compound.