High throughput screening assay systems in microscale fluidic devices

• US 7,041,509 B2
• Filed: 04/02/2002
• Issued: 05/09/2006
• Est. Priority Date: 06/28/1996
• Status: Expired due to Fees

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Parce, J. Wallace, Kopf-Sill, Anne R., Bousse, Luc J.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US10/115,275
• Publication Number:
  US 20020168688A1
• Time in Patent Office: 1,498 Days
• Field of Search: 422 55- 58, 435/6, 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, 436/514, 436/805, 436/806, 436/807, 436/809
• US Class Current: 436/514
• 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 for separating a subject material from a fluidic sample, comprising:

providing a microfluidic device having at least one reaction channel and at least one separation channel, said reaction channel having a first and a second incubation zone, and further the device having a transverse channel having a first end and a second end whereby the transverse channel intersects the reaction channel at the first end and the separation channel at the second end;

flowing a low ionic strength buffer in the reaction channel and a high ionic strength buffer in the separation channel;

introducing at least a first test compound into the reaction channel;

introducing a first component of a biochemical system into the reaction channel whereby the at least first test compound and the first component of the biochemical system flow through the first incubation zone of the reaction channel to form a reaction mixture;

introducing a second component of the biochemical system into said reaction channel whereby the second component and the first reaction mixture flow through the second incubation zone to form a second reaction mixture;

transporting the second reaction mixture through the transverse channel into the separation channel; and

separating the subject material from said second reaction mixture within the separation channel on the basis of differential flow rates or using size exclusion matrices.

2. The method of claim 1, wherein said first component of a biochemical system comprises at least one member of an antibody/antigen binding pair and said second component of the biochemical system comprises the other member of the antibody/antigen binding pair, wherein said antibody is specifically immunoreactive with said antigen.

3. The method of claim 1, wherein said first component of a biochemical system comprises an antibody and said second component of the biochemical system comprises an antigen specifically reactive with said antibody.

4. The method of claim 1, wherein said first component of a biochemical system comprises at least one member of a receptor/ligand binding pair.

5. The method of claim 4 wherein the subject material comprises a receptor/ligand complex and further said method comprising detection of the separation of the complex.

6. The method of claim 5, wherein the separating step comprises separation of the complex based on differential electrophoretic mobility of the complex and the ligand.

7. The method of claim 1, wherein said first component of a biochemical system comprises a receptor and said second component comprises a ligand specifically reactive with said receptor.

8. The method of claim 1, wherein said first component of a biochemical system comprises an enzyme.

9. The method of claim 8, wherein said second component of a biochemical system comprises a substrate for said enzyme.

10. The method of claim 1 further comprising:

detecting the subject material.

11. The method of claim 1, wherein the first and second components of the biochemical system are continuously introduced into the reaction channel.

12. The method of claim 1, wherein introducing the at least one test compound comprises periodically introducing a plurality of different test compounds into the reaction channel.

13. The method of claim 12, wherein each of the plurality of different test compounds are physically isolated from each other of said plurality of different test compounds.

14. A method of separating a sample material into at least two component species, comprising:

flowing said sample material in at least a first channel, said at least first channel comprising a first ionic strength buffer, said sample material confined in a discrete fluid region by low ionic strength spacer fluid regions;

transporting said sample material into a second channel via a transverse channel; and

separating said sample material into the at least two component species by flowing a second ionic strength buffer into said second channel whereby said sample material is no longer confined by the low ionic strength spacer fluid regions, wherein the separating of said sample material is caused by a differential electrophoretic mobility of said at least two component species within said second channel.

15. The method of claim 14, wherein said first ionic strength buffer has a lower ionic strength than said second ionic strength buffer.

16. The method of claim 14, wherein said separating step comprises removal of the low ionic strength spacer fluid regions.

17. The method of claim 14 further comprising detecting the at least two component species.

18. The method of claim 14, wherein said sample material and said first and second ionic strength buffers are flowed electroosmotically.

19. The method of claim 14, wherein an electrokinetic fluid direction system is used for flowing said sample material and said first and second ionic strength buffers into the first and second channels.

20. The method of claim 14, wherein at least one of the first, second, and transverse channels has at least one cross-sectional dimension in the range from about 0.1 μ

m to about 500 μ

m.