Sample analysis instrument

• US 6,656,431 B2
• Filed: 10/28/1999
• Issued: 12/02/2003
• Est. Priority Date: 05/18/1998
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Edwards, Floyd, Holl, Mark R., Klein, Gerald L., Morff, Robert
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Bex, Kathryn
• Application Number:
  US09/428,839
• Publication Number:
  US 20030152487A1
• Time in Patent Office: 1,496 Days
• Field of Search: 422/55, 422/58, 422/61, 422/68.1, 422/100, 422/82.05, 422/82.08, 422/104, 436/43, 436/164, 436/165, 436/172, 356/246, 356/73, 356/39
• US Class Current: 422/68.1
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4331 Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
• CPC Class Codes: B01F 25/4332 Mixers with a strong change of direction in the conduit for homogenizing the flow
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• 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 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 : pinch valves
• 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: 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 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502776 : specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/565 : Seals in general F16L
• CPC Class Codes: G01N 15/14 : Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: Y10T 156/1064 : Partial cutting [e.g., grooving or incising]
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• 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 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides an apparatus and method for storing a particle-containing liquid. The storage apparatus comprises a microfluidic convoluted flow channel having a plurality of particle capture regions. The storage channel is preferably an isotropic spatially periodic channel. Sedimented particles can be resuspended following storage. This invention further provides a microfluidic analysis cartridge having a convoluted storage channel therein. The sample analysis can use optical, electrical, pressure sensitive, or flow sensitive detection. A plurality of analysis channels can be included in a single cartridge. The analysis channels can be joined to reagent inlets for diluents, indicators or lysing agents. A mixing channel can be positioned between the reagent inlet and the analysis region to allow mixing and reaction of the reagent. The cartridge can include additional valves and pumps for flow management. The analysis cartridge can be a self-contained disposable cartridge having an integral waste storage container. This invention further provides a sheath flow assembly. The sheath flow assembly includes a sample channel and first and second sheath fluid channels positioned on either side of and converging with the sample channel. The assembly also includes upper and lower sheath fluid chambers positioned above and below and converging with the sample channel. The flow cartridges of this invention can be formed by molding, machining or etching. In a preferred embodiment they are laminated. This invention further provides a method of fabricating a laminated microfluidic flow device. In the method, flow elements are formed in rigid sheets and abutting surfaces of the sheets are bonded together.

Claims

1. A sample instrument for use with a fluidic cartridge, said cartridge having first and second analysis regions, said instrument comprising:

a cartridge holder for engaging said cartridge;

a flow cytometric measuring apparatus positioned to be optically coupled with said first analysis region, said flow cytometric measuring apparatus comprising a first light source, a first photodetector and a second photodetector; and

an absorption measuring apparatus positioned to be optically coupled with said second analysis region, said absorption measuring apparatus comprising a second light source and a third photodetector.

2. The instrument of claim 1 wherein said first photodetector is positioned to collect scattered light from said first analysis region.

3. The instrument of claim 2 wherein said second photodetector is positioned to collect scattered or fluorescent light from said first analysis region.

4. The instrument of claim 1 wherein said cartridge has cartridge alignment markings thereon and wherein said holder has alignment markings thereon to mate with said cartridge alignment markings.

5. The instrument of claim 1 wherein said cartridge contains a pump interface and wherein said instrument further comprises a pump mechanism positioned to couple with said pump interface.

6. The instrument of claim 5 wherein said pump interface is a syringe pump interface and wherein said pump mechanism is a syringe pump.

7. The instrument of claim 1 wherein said cartridge contains a valve interface and wherein said instrument further comprises a valve mechanism positioned to couple with said valve interface.

8. The instrument of claim 7 wherein said valve interface is a pinch valve interface and wherein said valve mechanism is a pinch valve mechanism.

9. The instrument of claim 1 wherein said cartridge is disposable.

10. The instrument of claim 1 wherein said first light source comprises a laser.

11. The instrument of claim 1 wherein said second light source and said third photodetector are positioned to be on opposite sides of said cartridge.