Microplate with an integrated microfluidic system for parallel processing minute volumes of fluids

• US 20030224531A1
• Filed: 05/29/2002
• Published: 12/04/2003
• Est. Priority Date: 05/29/2002
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Yin, Hongfeng, Brennen, Reid A., Killeen, Kevin Patrick
• Application Number:
  US10/157,803
• Publication Number:
  US 20030224531A1
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: G01N 2030/8435 for chemical reaction
• CPC Class Codes: G01N 30/461 with serial coupling of separation columns
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray
• CPC Class Codes: H01J 49/0018 Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
• CPC Class Codes: H01J 49/107 Arrangements for using several ion sources
• CPC Class Codes: H01J 49/165 Electrospray ionisation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A microanalytical device is provided for conducting multiple chemical and/or biochemical reactions and analyzing multiple sample fluids in parallel using minute volumes of reaction or sample fluid. The devices comprises a well plate with an integrated microfluidic system containing processing compartments such as microcavities, microchannels and the like, that are in fluid communication with electrospray emitters. The novel microanalytical device can be used in a variety of chemical and biochemical contexts, including mass spectroscopy, chromatographic, electrophoretic and electrochromatographic separations, screening and diagnostics, and chemical and biochemical synthesis. The devices may be formed from a material that is thermally and chemically stable and resistant to biofouling, significantly reducing electroosmotic flow and unwanted adsorption of solute.

Claims

1. A microanalytical device in which a plurality of chemical and biochemical reactions can be conducted in parallel, comprising a wellplate having integrated microfluidics and electrospray emitters that are each capable of delivering a sample to a mass spectrometer.

2. The microanalytical device of claim 1, wherein the integrated microfluidics are formed by the joining of:

(a) a microfluidic housing having first and second substantially planar opposing surfaces, with a plurality of cavities and microchannels formed in the first substantially planar opposing planar surface, wherein each cavity is in fluid communication with both (i) an upstream microchannel that is in turn in fluid communication with an associated inlet port and (ii) a downstream microchannel that is in fluid communication with an associated outlet port that is in turn in fluid communication with an associated electrospray emitter; and

(b) a cover plate affixed to the first substantially planar surface, said cover plate in combination with the cavities and microchannels defining the plurality of independent, parallel sample processing compartments,

wherein the wellplate may be integrated with the microfluidic housing or the cover plate and each well in the well plate is capable of fluid communication with an inlet port of a sample processing compartment.

3. The microanalytical device of claim 2, wherein the inlet ports are housed in the microfluidic housing and the well plate is integrated with the microfluidic housing.

4. The microanalytical device of claim 2, wherein the inlet ports are housed in the cover plate and the well plate is integrated with the cover plate.

5. The microanalysis device of claim 1, wherein the well plate comprises at least 96 wells.

6. The microanalysis device of claim 1, wherein the electrospray emitters are formed of the same material the substrate.

7. The microanalytical device of claim 1, wherein the device is comprised of a polymeric material.

8. The microanalytical device of claim 7, wherein the polymeric material is selected from the group consisting of polyimides, polycarbonates, polyesters, polyamides, polyethers, polyurethanes, polyfluorocarbons, polystyrenes, poly(acrylonitrile-butadiene-styrene), polymethyl methacrylate, polyolefins, and copolymers thereof.

9. The microanalytical device of claim 8, wherein the polymeric material is polyimide or polyetheretherketone.

10. The microanalytical device of claim 2, wherein the integrated microfluidics are treated to enhance thermal stability and biofouling resistance.

11. The microanalytical device of claim 2, wherein the upstream microchannel in combination with the cover plate forms an upstream microcolumn, and the downstream microchannel in combination with the cover plate forms a downstream microcolumn.

12. The microanalytical device of claim 1, further including motive means to move fluid from each well through the sample processing compartments.

13. The microanalytical device of claim 12, wherein the motive means is not directly housed on the microanalytical device.

14. The microanalytical device of claim 13, wherein the motive means comprises a means for applying a voltage differential.

15. The microanalytical device of claim 12, wherein the motive means comprises a means for applying a pressure differential.

16. The microanalytical device of claim 2, wherein the fluid communication between each well and the inlet port is provided by spiral capillaries.

17. The microanalytical device of claim 2, wherein each cavity is sized to contain approximately 1 nL to approximately 500 μ

L of fluid.

18. The microanalytical device of claim 17, wherein each cavity is sized to contain approximately 100 nL to approximately 10 μ

L of fluid.

19. The microanalytical device of claim 2, wherein each microchannel is approximately 1 μ

m to 200 μ

m in diameter.

20. The microanalytical device of claim 19, wherein each microchannel is approximately 10 82 m to 75 μ

m in diameter.

21. A method for transporting a plurality of liquid samples to a mass spectrometer in parallel using at most 500 μ

l of each liquid sample, the method comprising;

(a) introducing approximately 1 nL to about approximately 500 μ

L of each liquid sample into a separate well located in a microanalytical device according to claim 1,

(b) applying a motive force to the device to move each liquid sample through the microanalytical device; and

(c) introducing each liquid sample into the mass spectrometer via the spray emitters.

22. The method of claim 21, wherein the sample fluids undergo a chemical reaction while in the microanalytical device.