High throughput screening assay systems in microscale fluidic devices

• US 6,306,659 B1
• Filed: 11/20/1998
• Issued: 10/23/2001
• 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.
• Assistant Examiner(s): PHAM, MINH QUAN K
• Application Number:
  US09/196,535
• Time in Patent Office: 1,068 Days
• Field of Search: 436/47, 436/518, 436/514, 435/4, 435/164, 435/6, 435/810, 435/287.3, 422/55, 422/58, 422/102, 422/63, 422/65
• 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

An apparatus for analyzing a plurality of compounds is used in conjunction with microfluidic devices for performing high throughput screening assays. A conveyor system delivers libraries of compounds to a microfluidic device which 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. An apparatus for analyzing a plurality of test compounds, said apparatus comprising:

(i) a platform configured to receive at least one microfluidic device in a microfluidic device holding region in or on the platform;

(ii) a multiwell plate stacking region for stacking a plurality of multiwell plates;

(iii) a plate conveyor system which, during operation of the apparatus, transports at least one multiwell plate from the multiwell plate stacking region to a position proximal to the microfluidic device holding region of the platform, thereby facilitating contact between the at least one multiwell plate and the at least one microfluidic device during operation of the apparatus; and

,

(iv) a sensor element mounted proximal to said platform for monitoring an output from the microfluidic device when said device is mounted in or on the platform.

2. An apparatus according to claim 1, further comprising:

a microfluidic device mounted in the microfluidic device holding region of the platform said device having a sample input channel fluidly connected to a channel system comprising at least one channel having at least one cross-sectional dimension between about 0.1 μ

m and about 500 μ

m.

3. An apparatus according to claim 1, further comprising:

(v) an armature configured for moving said platform relative to the plate conveyor system, thereby providing for contact between the at least one microfluidic device and the at least one multiwell plate during operation of the apparatus.

4. An apparatus according to claim 1, further comprising:

(vi) a buffer dispensing system proximal to said plate conveyor system for filling said plurality of multiwell plates.

5. An apparatus according to claim 2, further comprising:

(vii) said microfluidic device mounted in the microfluidic device holding region of the platform and an adapter for mounting a plurality of electrodes in reservoirs of said microfluidic device, which reservoirs are fluidly connected to at least one channel.

6. An apparatus according to claim 1, farther comprising:

(viii) a plurality of multiwell plates in the plate stacking region of the apparatus.

7. An apparatus according to claim 6, wherein said multiwell plates contain said plurality of test compounds.

8. An apparatus according to claim 1, wherein said platform is configured to receive a plurality of microfluidic devices.

9. An apparatus according to claim 2, further comprising:

said microfluidic device mounted on said platform wherein said microfluidic device holding region comprises an opening through which a microfluidic channel fluidly connected to said microfluidic substrate contacts a portion of said at least one multiwell plate during operation of the apparatus.

10. An apparatus according to claim 2, wherein said microfluidic device comprises at least one sample input port.

11. An apparatus according to claim 10, wherein said at least one sample input port comprises a pipettor element fluidly coupled to said channel system of said microfluidic device.

12. An apparatus according to claim 1, wherein said conveyor system is a unidirectional conveyor system.

13. An apparatus according to claim 2, wherein said microfluidic device comprises reservoirs in fluid communication with said channel system, said apparatus further comprising an electrokinetic controller comprising a plurality of electrodes which mate with said reservoirs.

14. An apparatus according to claim 11, wherein said sensor element for monitoring said output is a component of an optical detection system.

20. The apparatus of claim 1, wherein the plate conveyor system is mounted under the platform.

15. A system for analyzing a plurality of test compounds, said system comprising:

(i) an apparatus for handling a plurality of multiwell plates and at least one microfluidic substrate, the apparatus comprising a multiwell plate movement mechanism for moving said multiwell plates into proximity with said at least one microfluidic substrate, wherein the apparatus moves at least one of the multiwell plates into contact with the at least one microfluidic substrate during operation of the system, wherein said at least one microfluidic substrate comprises a channel system with a channel cross sectional dimension between about 0.1 μ

m and about 500 μ

m, wherein a signal produced by one or more of said test compounds is monitored by a detector mounted proximal to said microfluidic substrate; and

,

(ii) a computer to record said signal, said computer comprising;

software for controlling fluid flow and direction within said at least one microfluidic, substrate thereby controlling flow of said plurality of test compounds, wherein the computer and the detector are operably connected.

16. A system according to claim 15, said system further comprising:

an adapter module, said adapter module providing an interface between said computer and said apparatus.

17. A system according to claim 16, wherein said adapter module connects said computer and said apparatus by at least one of:

electrical leads connected to the reservoir based electrodes, a power input, an output from a detection system or a data relay.

18. A system according to claim 15, further comprising:

an environmental control system, said environmental control system providing optimum temperature for said system.

19. A system according to claim 15, further comprising:

an optical detection system coupled to said channel system of said microfluidic substrate.