Implementation of microfluidic components, including molecular fractionation devices, in a microfluidic system

• US 7,514,000 B2
• Filed: 06/30/2006
• Issued: 04/07/2009
• Est. Priority Date: 09/09/2002
• Status: Expired due to Term

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome Inc.
• Inventors: Trikha, Jaishree, Deshpande, Manish, Gilbert, John R.
• Primary Examiner(s): Menon; Krishnan S
• Application Number:
  US11/479,125
• Publication Number:
  US 20070075010A1
• Time in Patent Office: 1,012 Days
• Field of Search: None
• US Class Current: 210/635
• CPC Class Codes: B01D 2313/13 Specific connectors
• CPC Class Codes: B01D 2313/40 Adsorbents within the flow path
• CPC Class Codes: B01D 2325/028 Microfluidic pore structures
• CPC Class Codes: B01D 2325/12 Adsorbents being present on the surface of the membranes or in the pores
• CPC Class Codes: B01D 63/087 Single membrane modules
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B01D 67/0034 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 67/0062 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/047 Additional chamber, reservoir
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0666 Solenoid valves
• CPC Class Codes: B01L 3/06 : Crystallising dishes
• 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 3/50273 : 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 3/502753 : 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: C02F 2209/36 : Biological material, e.g. enzymes or ATP
• CPC Class Codes: C30B 29/58 : Macromolecular compounds
• CPC Class Codes: C30B 7/00 : Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44773 : Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: Y10S 977/786 : Fluidic host/matrix containing nanomaterials
• CPC Class Codes: Y10T 156/10 : Methods of surface bonding and/or assembly therefor

Abstract

A system and method for integrating microfluidic components in a microfluidic system enables the microfluidic system to perform a selected microfluidic function. A capping module includes a microfluidic element for performing a microfluidic function. The capping module is stacked on a microfluidic substrate having microfluidic plumbing to incorporate the microfluidic function into the system. The microfluidic element may comprise a matrix having an affinity for selected molecules in a sample. The matrix binds, reacts with and/or retains the selected molecules without affecting other molecules in the sample.

Claims

1. A method for protein expression profiling, comprising the steps of:

coupling a plurality of molecular fractionation devices to a substrate having a plurality of microchannels formed therein, wherein each molecular fractionation device includes a matrix disposed in a chamber of the molecular fractionation device, a first outlet connector port, and, a first inlet connector port placing the matrix in communication with an exterior surface of the molecular fractionation device, and wherein the first outlet connector port of each molecular fractionation device aligns with a communication port of a microchannel in the substrate when the molecular fractionation device is coupled thereto;

coupling the plurality of molecular fractionation devices to each other, wherein the plurality of molecular fractionation devices are coupled by coupling a second outlet connector port of one molecular fractionation device to a second inlet connector port of another molecular fractionation device;

closing each of the first outlet connector ports;

fractionating a protein into a plurality of fractions using the plurality of molecular fractionation devices;

opening each of the first outlet connector ports;

closing each of the second outlet connector ports; and

eluting each of said plurality of fractions from each of the plurality of molecular fractionation devices by passing a release solution through each respective one of the first outlet connector port into the coupled microchannel in the substrate as bands of different affinities.

2. The method of claim 1, further comprising the step of dialyzing the eluted bands using a semipermeable membrane.

3. The method of claim 2, further comprising the step of injecting one of said eluted bands into a capillary electrophoresis column.

4. The method of claim 3, further comprising the step of electrophoretically separating said band into a plurality of sub-bands.

5. The method of claim 4, further comprising the step of ejecting one of said sub-bands from the electrophoresis column to a plate.

6. The method of claim 5, wherein the sub-band is ejected to one of a multiwell plate and a MALDI spotting plate.