Miniaturized genetic analysis systems and methods

• US 6,168,948 B1
• Filed: 01/12/1998
• Issued: 01/02/2001
• Est. Priority Date: 06/29/1995
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Rava, Richard P., Lipshutz, Robert J., Fodor, Stephen P. A., Anderson, Rolfe C.
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US09/005,985
• Time in Patent Office: 1,086 Days
• Field of Search: 435/6, 435/7.1, 435/7.92, 435/287.1, 435/287.2, 435/287.9, 435/288.6, 436/518, 436/523, 436/527, 436/528, 436/530, 436/89, 436/90, 436/94, 422/68.1, 422/100, 422/101, 422/102, 536/25.4, 536/75.41, 210/656, 210/198.2
• US Class Current: 435/287.2
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01F 33/25 Mixers with loose mixing elements, e.g. loose balls in a receptacle
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• 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 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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 3/50273 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: 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 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: Y10S 366/03 Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow

Abstract

The present invention provides a miniaturized integrated nucleic acid diagnostic device and system which includes a nucleic acid extraction zone including nucleic acid binding sites.

Claims

1. A nucleic acid extraction device, comprising:

a body having at least one chamber with at least one inlet channel;

a porous flow-through deformable plug disposed within the chamber, the deformable plug having nucleic acid binding properties; and

a flexible diaphragm for compressing said plug thereby removing trapped liquids.

2. The nucleic acid extraction device of claim 1, wherein

the flexible diaphragm is disposed between a pneumatic port and the deformable plug, the device further comprising a pressure system for displacing the flexible diaphragm to draw a sample through the inlet channel into the chamber.

3. A nucleic acid extraction device, comprising:

a body having at least one chamber with at least one inlet channel, wherein the chamber comprises a textured interior wall surface having nucleic acid binding properties;

a porous flow-through plug disposed within the chamber, the plug having nucleic acid binding properties, and

a piezoelectric crystal adapted to acoustically agitate a nucleic acid sample, and wherein the piezoelectric crystal is mounted to the chamber opposite the textured interior wall surface of the chamber.

4. A biological sample refinement device, comprising:

a body having at least one microchamber with at least one inlet channel;

a structure disposed within the microchamber, the structure having binding sites thereon; and

a fluid distribution system for delivering a biological sample into the microchamber such that at least a portion of the sample contacts the binding sites, the fluid distribution system being adapted to deliver an adjustable volume of metered elution buffer into the microchamber.

5. The device of claim 4, wherein the structure comprises a substantially planar wall with a plurality of beads attached thereto.

6. The device of claim 4, wherein,

the binding sites comprise agents selected from the group consisting of acids, bases, silanes, polylysine, tethered antibodies, nucleic acids and Poly-T DNA.