High throughput screening assay systems in microscale fluidic devices

• US 6,150,180 A
• Filed: 07/26/1999
• Issued: 11/21/2000
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Caliper Holdings Incorporated
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Parce, John Wallace, Kopf-Sill, Anne R., Bousse, Luc J.
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): PHAM, MINH QUAN K
• Application Number:
  US09/360,782
• Time in Patent Office: 484 Days
• Field of Search: 435/6, 435/4, 435/7.2, 435/7.21, 435/259, 435/291, 435/287.1, 435/287.2, 435/287.9, 435/288.4, 435/288.5, 435/288.7, 435/810, 435/970, 436/164, 436/518, 436/524, 436/527, 436/531, 436/533, 436/534, 436/805, 436/806, 436/807, 436/809, 436/514, 422/55, 422/56, 422/57, 422/58
• US Class Current: 506/7
• 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 2200/0605 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 2200/0689 Sealing
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• 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 2300/0877 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 3/5025 for parallel transport of multiple samples
• 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: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• 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 33/5044 : involving specific cell types
• 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 33/5094 : for blood cell populations red blood cells G01N33/80
• 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 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

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 microfluidic device that comprises;

a substrate having a plurality of discrete reaction channels disposed therein, each reaction channel comprising a detection window;

a plurality of sources of a first component of a biochemical system disposed in the substrate, each source of first component being fluidly connected to a different one of the plurality of discrete reaction channels; and

a plurality of sources of a second component of a biochemical system disposed in the substrate, each of the sources of second component being fluidly connected to a separate one of the plurality of discrete reaction channels;

transporting the first and second components of the biochemical system into the reaction channel;

introducing a different one of the plurality of test compounds into each of the plurality of discrete reaction channels, wherein the test compound contacts the first and second components; and

detecting an effect, if any of each of the different test compounds on the interaction of the first and second components at the detection windows in each of the plurality of discrete reaction channels.

2. The method of claim 1, wherein the first and second components are transported into the plurality of reaction channels electrokinetically.

3. The method of claim 1, wherein the first and second components are pumped into the plurality of discrete reaction channels.

4. The method of claim 1, wherein the interaction of the first and second components produces a fluorescent signal, and the detecting step comprises detecting a change in the fluorescent signal in the presence of the test compound, relative to a level of fluorescent signal in the absence of the test compound.

5. The method of claim 1, wherein the introducing step comprises separately transporting test compounds from each of a plurality of separate sources of test compound into each of the plurality of discrete reaction channels.

6. The method of claim 5, wherein each of the plurality of test compounds is transported from each source of test compound to a separate reaction channel via a separate capillary having a capillary channel disposed therein, each capillary channel being in fluid communication with a different reaction channel.

7. The method of claim 5, wherein the introducing step comprises transporting each of the plurality of test compounds into a separate capillary channel disposed in a capillary tube, each capillary channel being provided in fluid communication with a separate one of the plurality of discrete reaction channels.

8. The method of claim 7, wherein the introducing step further comprises moving each of the plurality of test compounds from the separate capillary channel into the discrete reaction channel fluidly connected thereto.

9. The method of claim 1, wherein the detecting step comprises detecting an amount of a product of the interaction of the first and second components at the detection window.

10. The method of claim 9, wherein the product comprises a fluorescent label, and the detecting step comprises detecting the fluorescent label at the detection widow.

11. The method of claim 1, wherein the detecting step comprises detecting a decrease in an amount of at least one of the first and second components at the detection window.

12. The method of claim 11, wherein the at least one of the first and second components has a fluorescent label associated therewith and the detecting step comprises detecting the fluorescent label.

13. The method of claim 1, wherein the interaction of the first and second components produces a product having a mobility in the reaction channel that is different from at least one of the first and second components in the reaction channel, and wherein the detecting step comprises detecting an increase in product or a decrease in at least one of the first and second components by virtue of the different mobility of the product relative to the mobility of at least one of the first and second components.

14. The method of claim 13, wherein the first component and the product comprise the same detectable label, and wherein the mobility of the first component in the discrete reaction channel is different from that of the product.