Electrokinetic pumping

• US 5,985,119 A
• Filed: 05/10/1996
• Issued: 11/16/1999
• Est. Priority Date: 11/10/1994
• Status: Expired due to Term

• Current Assignee: Sarnoff Corporation (SRI International, Inc.)
• Original Assignee: Sarnoff Corporation (SRI International, Inc.)
• Inventors: Levine, Aaron W., Chiang, William, Zanzucchi, Peter John, Moroney, Richard Morgan III, Cherukuri, Satyam Choudary, McBride, Sterling Edward, Burton, Charlotte Anna
• Primary Examiner(s): Warden, Robert
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US08/645,966
• Time in Patent Office: 1,285 Days
• Field of Search: 204/450, 204/600, 422/129, 422/131, 422/149, 422/188
• US Class Current: 204/450
• CPC Class Codes: B01F 25/41 Mixers of the fractal type
• CPC Class Codes: B01F 33/3032 using magneto-hydrodynamic [MHD] phenomena to mix or move the fluids
• CPC Class Codes: B01F 35/7182 with means for feeding the material with a fractal or tree-type distribution in a surface
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00358 electrode driven
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00488 by rotation of the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 : the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 : The surface being organic
• CPC Class Codes: B01J 2219/00612 : the surface being inorganic
• CPC Class Codes: B01J 2219/00626 : Covalent
• CPC Class Codes: B01J 2219/00635 : by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/0068 : Means for controlling the apparatus of the process
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00698 : Measurement and control of process parameters
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00783 : Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00835 : Comprising catalytically active material
• CPC Class Codes: B01J 2219/00853 : Employing electrode arrangements
• CPC Class Codes: B01J 2219/00873 : Heat exchange
• CPC Class Codes: B01J 2219/00891 : Feeding or evacuation
• CPC Class Codes: B01J 2219/00952 : Sensing operations
• CPC Class Codes: B01J 2219/00961 : Temperature
• CPC Class Codes: B01J 2219/00995 : Mathematical modeling
• CPC Class Codes: B01J 4/02 : for feeding measured , i.e. prescribed quantities of reagents
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2300/0874 : Three dimensional network
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/084 : Passive control of flow resistance
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: C07C 17/25 : by splitting-off hydrogen halides from halogenated hydrocarbons
• CPC Class Codes: C07C 17/263 : by condensation reactions
• CPC Class Codes: C07C 45/46 : Friedel-Crafts reactions
• CPC Class Codes: C07C 45/68 : by increase in the number of carbon atoms
• CPC Class Codes: C07C 45/69 : by addition to carbon-to-carbon double or triple bonds
• CPC Class Codes: C07C 45/72 : by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: F04B 17/00 : Pumps characterised by combination with, or adaptation to, specific driving engines or motors
• CPC Class Codes: F04B 19/006 : Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: H02N 11/006 : Motors

Abstract

The invention provides methods of performing a synthetic process in a liquid distribution system having reaction cells, by pumping at least one reagent into a reaction cell.

Claims

1. A method of performing a chemical process in a liquid distribution apparatus that includes a substrate formed of two or more layers having reagent sources, reaction cells, channels of capillary dimensions, and electrode-based pumps, wherein at least a first said reagent source contains a first reagent, the channels provide fluid communication through the thickness of at least one substrate layer from said reagent sources to said reaction cells, and said electrode-based pumps comprise electrodes that contact the channels, the method comprising:

(a) applying a voltage across the electrodes of a first said pump that contacts a channel in order to move said first reagent into a reaction cell; and

(b) contacting the first reagent with a second reagent that is in said reaction cell as part of said chemical process.

2. The method of claim 1, wherein the chemical process is a catabolic or anabolic reaction.

3. The method of claim 1, wherein the chemical process is a an oxidation or reduction.

4. The method of claim 3, wherein the chemical process is an oxidation and the first reagent is an m-chloroperbenzoic acid hydrogen peroxide, or KMnO₄.

5. The method of claim 3, wherein the chemical process is a reduction and the reagents are selected from the group consisting of LiAlH₄ and lithium borohydride.

6. The method of claim 1, wherein the process is an amide formation, a Mitsunobu reaction, a Suzuki coupling, a Stille coupling, an alkylation of an amine, an acylation of an amine, an alkylation of a ketone, a reductive amination, a sulfonamide formation, a DNA synthesis, a cycloaddition, a Mannich reaction, a Diels Alder reaction, a Wittig reaction, a Heck reaction, an elimination of a leaving group or a condensation reaction.

7. The method of claim 6, wherein the chemical process is amide formation and the reagents are selected from the group consisting of dehydration reagents, 2,3-dichloro-5,6-dicyano-1,4-benzoquinonone, protected amino acids, and N-methyl morpholine.

8. The method of claim 7, wherein the dehydration reagent is selected from o-benzotriazol-1-yl-N,N,N'"'"',N'"'"'-tetramethyluroniumhexafluorophosphate, 1-hydroxybenzotriazole hydrate, dicyclohexylcarbodiimide, and diisopropyl carbodiimide.

9. The method of claim 6, wherein the chemical process is a Mitsunobu reaction and the first reagent is a phenol, an alcohol, a diethylazodicarboxylate, a triphenylphosphine, or a N-methyl morpholine.

10. The method of claim 6, wherein the chemical process is Suzuki coupling and the first reagent is a halide, a palladium (0) catalyst, an aryl boronic acid, a triethyl amine, or a dimethyl formamide.

11. The method of claim 6, wherein the chemical process is Stille coupling and the reagents are selected from the group consisting of halide, palladium (0) catalyst, aryl stannate, N-methyl pyrrolidone and triphenyl arsine.

12. The method of claim 6, wherein the chemical process is alkylation or acylation of an amine and the reagents are selected from the group consisting of, tosylate compounds, halide compounds, amine compounds, N-methyl pyrrolidone, and phosgene.

13. The method of claim 6, wherein the chemical process is alkylation of a ketone and the reagents are selected from the group consisting of amine, ketone, lithium diiosopropyl amine, tetrahydrofuran, and alkyl iodide.

14. The method of claim 6, wherein the chemical process is reductive amination and the reagents are selected from the group consisting of amine, aldehyde, sodium cyanoborohydride, sodium triacetyoxyborohydride, borohydrate pyridine, and methylene chloride.

15. The method of claim 6, wherein the chemical process is sulfonamide formation and the reagents are selected from the group consisting of amines, sulfonyl chloride, and dimethylformamide.

16. The method of claim 6, wherein the chemical process is nucleic acid synthesis and the reagents are selected from the group consisting of oligonucleotides and phosphates.

17. The method of claim 6, wherein the chemical process is cycloaddition and the reagents are selected from the group consisting of peracids, substituted alkenes, diazo compounds, azide, nitrites, azomethine ylide, nitrones, and carbonyl oxides.

18. The method of claim 6, wherein the chemical process is a Mannich reaction and the reagents are selected from the group consisting of aldehydes, ketones, amine salts, amides, acids, and bases.

19. The method of claim 6, wherein the chemical process is a Diels Alder reaction and the reagents are selected from the group consisting of substituted alkenes and dienes.

20. The method of claim 6, wherein the chemical process is a Wittig reaction and the reagents are selected from the group consisting of triphenylphosphines and substituted alkenes.

21. The method of claim 6, wherein the chemical process is a Heck reaction and the reagents are selected from the group consisting of a palladium (0) catalyst, substituted alkenes, substituted halides, and triethylamines.

22. The method of claim 6, wherein the chemical process is elimination of a leaving group and the reagents are selected from the group consisting of alkyl and halides and bases.

23. The method of claim 1, wherein the chemical process is employed to synthesize a compound selected from the group consisting of a polymeric organic compound, an oligonucleotide, a peptide.

24. The method of claim 1, wherein the reagent is selected from the group consisting of carboxylic acids, carbodiimides, sulfonamides, amines, alcohols, pyridines, azodicarboxylates, carbazoles, azobenzenes, amino N-oxides, 1,4-benzoquinone and ammonium perruthenate.

25. The method of claim 1, wherein the second reagent is coupled to a solid support in the reaction cell.

26. The method of claim 25, wherein the solid support is one or more polymer beads.

27. The method of claim 1, wherein the apparatus further comprises a second reagent source containing a second reagent, and the method comprises applying a voltage across two said electrodes of a second pump to selectively move the second liquid into the reaction cell of step (a).

28. The method of claim 1 wherein the apparatus further comprises capillary barriers interposed in the channels to prevent liquid flow into the reaction cells in the absence of activating an associated electrode-based pump and wherein the voltage applied to two said electrodes of the first pump is effective to move the first reagent past a capillary barrier.