Microfluidic size-exclusion devices, systems, and methods

• US 7,214,348 B2
• Filed: 01/03/2003
• Issued: 05/08/2007
• Est. Priority Date: 07/26/2002
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Fawcett, Adrian, Shigeura, John, Bryning, Zbigniew T., Desmond, Sean M., Lim, Gary, Bordenkircher, Gary, Freudenthal, Jacob K.
• Primary Examiner(s): SINES, BRIAN J
• Application Number:
  US10/336,706
• Publication Number:
  US 20040018116A1
• Time in Patent Office: 1,586 Days
• Field of Search: 422/50, 422/55, 422/68.1, 422/100, 422/101, 422/102, 422/103, 422/104, 436/43, 436/63, 436/174, 436/175, 436/177, 436/178, 436/180
• US Class Current: 422/502
• 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: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• 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 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0633 with moving parts
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• 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: C12Q 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/17 : Nitrogen containing
• CPC Class Codes: Y10T 436/173845 : Amine and quaternary ammonium
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25125 : Digestion or removing interfering materials
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Microfluidic devices, assemblies, and systems are provided, as are methods of manipulating micro-sized samples of fluids. Microfluidic devices having a plurality of specialized processing features are also provided.

Claims

1. A microfluidic device comprising:

a substrate having a first surface, a second surface opposing the first surface, and a thickness;

a first channel formed in the substrate and extending in a first direction, the first channel having a first cross-sectional area defined by at least a first minimum dimension and a first depth, the first depth extending in a direction normal to the first surface and toward the second surface;

a second channel formed in the substrate and extending in a second direction, the second channel having a second cross-sectional area defined by at least a second minimum dimension and a second depth, the second depth extending in a direction normal to the first surface and toward the second surface;

a fluid communication formed in the substrate between the first channel and the second channel and having a third cross-sectional area defined by at least a third minimum dimension, wherein the third cross-sectional area is less than the first cross-sectional area; and

a particulate flow-restricting material disposed in the first channel and comprising flow-restricting particles, wherein at least 10% by weight of the flow-restricting particles comprises flow-restricting particles having a particle diameter that is less than the third minimum dimension.

2. The microfluidic device of claim 1, wherein the first direction and the second direction are aligned with one another at the fluid communication.

3. The microfluidic device of claim 1, wherein at least one of the first channel and the second channel includes a cross-section that has a round shape.

4. The microfluidic device of claim 1, wherein at least 50% by weight of the flow-restricting particles comprises flow-restricting particles having a particle diameter that is less than the third minimum dimension.

5. The microfluidic device of claim 1, wherein at least 95% by weight of the flow-restricting particles comprises flow-restricting particles having a particle diameter that is less than the third minimum dimension.

6. The microfluidic device of claim 1, wherein the flow-restricting particles have particle diameters that are less than the second minimum dimension.

7. The microfluidic device of claim 1, wherein the flow-restricting material includes a gel filtration material disposed in the first channel and, wherein the gel filtration material has an average diametrical cross-sectional area that is less than the third cross-sectional area.

8. The microfluidic device of claim 1, wherein the average diametrical cross-sectional area of the flow-restricting particles is from about 0.1 to about 0.2 times the third cross-sectional area.

9. The microfluidic device of claim 1, comprising a pile-up of flow-restricting particles at the fluid communication.

10. The microfluidic device of claim 1, wherein the flow-restricting material includes:

a first flow-restricting material having particles of a first average diameter packed-together at the fluid communication, and a second flow-restricting material having particles of a second average diameter packed-together in the first channel and adjacent the packed-together first flow-restricting material, and wherein the average diameter of the first flow-restricting material particles is greater than the average diameter of the second flow-restricting material particles, and the second packed-together flow-restricting material is spaced further from the second channel than is the packed-together first flow-restricting material.

11. The microfluidic device of claim 1, further comprising a second material disposed in at least one of the first and second channels and comprising particles that hybridize with nucleic acid sequences.

12. The microfluidic device of claim 1, wherein the fluid communication includes a tapered transition region from the first channel to the second channel.

13. The microfluidic device of claim 12, wherein the tapered transition region has a conical shape.

14. The microfluidic device of claim 1, further comprising a first cover that contacts the first surface of the substrate and covers at least one of the first channel, the second channel, and the fluid communication.