Integrated active flux microfluidic devices and methods

(54) INTEGRATED ACTIVE FLUX

MICROFLUIDIC DEVICES AND METHODS

(75) Inventors: Stephen R. Quake, San Marino, CA (US); Hou-Pu Chou, Foster City, CA (US)

(73) Assignee: California Institute of Technology,

Pasadena, CA (US)

( * ) Notice: Subject to any disclaimer, the term ol this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.

(21) Appl. No.: 09/875,438

(22) Filed: Jun. 5, 2001

(65) Prior Publication Data

US 2002/0037499 Al Mar. 28, 2002

(63) (60)

(51)

Related U.S. Application Data

Continuation-in-part of application No. 09/724,548, filed on Nov. 28, 2000.

Provisional application No. 60/249,360, filed on Nov. 16, 2000, provisional application No. 60/211,309, filed on Jun. 13, 2000, and provisional application No. 60/209,243, filed on Jun. 5, 2000.

Int. CI.7 C12Q 1/68; C12P 19/34;

C12M 1/34; C07H 21/02; C07H 21/04

(52) U.S. CI 435/6; 435/7.1; 435/91.1;

435/91.2; 435/287.2; 536/22.1; 536/23.1; 536/24.3; 536/24.31; 536/24.32; 536/24.33

(58) Field of Search 435/6, 7.1, 91.1,

435/91.2, 287.2; 536/22.1, 23.1, 24.3-24.33

(56) References Cited

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(List continued on next page.)

Primary Examiner—Jeffrey Siew

(74) Attorney, Agent, or Firm—Darby & Darby

The invention relates to a microlabricated device for the rapid detection ol DNA, proteins or other molecules associated with a particular disease. The devices and methods ol the invention can be used for the simultaneous diagnosis ol multiple diseases by detecting molecules (e.g. amounts ol molecules), such as polynucleotides (e.g., DNA) or proteins (e.g., antibodies), by measuring the signal ol a detectable reporter associated with hybridized polynucleotides or antigen/antibody complex. In the microlabricated device according to the invention, detection ol the presence ol molecules (i.e., polynucleotides, proteins, or antigen/ antibody complexes) are correlated to a hybridization signal from an optically-detectable (e.g. fluorescent) reporter associated with the bound molecules. These hybridization signals can be detected by any suitable means, for example optical, and can be stored for example in a computer as a representation ol the presence ol a particular gene. Hybridization probes can be immobilized on a substrate that forms part ol or is exposed to a channel or channels ol the device that form a closed loop, for circulation ol sample to actively contact complementary probes. Universal chips according to the invention can be labricated not only with DNA but also with other molecules such as RNA, proteins, peptide nucleic acid (PNA) and polyamide molecules.

21 Claims, 22 Drawing Sheets

OTHER PUBLICATIONS

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* cited by examiner