Microfluidic apparatus and method for enriching and analyzing biological cells

• US 20030224436A1
• Filed: 05/16/2003
• Published: 12/04/2003
• Est. Priority Date: 07/30/1996
• Status: Abandoned Application

• Current Assignee: Alan K. Hauser, Alexander P. Sassi, Herbert H. Hooper, Robert J. Nelson, Sharat Singh, Stephen J. Williams
• Original Assignee: Alan K. Hauser, Alexander P. Sassi, Herbert H. Hooper, Robert J. Nelson, Sharat Singh, Stephen J. Williams
• Inventors: Nelson, Robert J., Williams, Stephen J., Hauser, Alan K., Sassi, Alexander P., Singh, Sharat, Hooper, Herbert H.
• Application Number:
  US10/439,951
• Publication Number:
  US 20030224436A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2200/0631 Purification arrangements, e.g. solid phase extraction [SPE]
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• 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 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• 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 3/502753 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 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• 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: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/5002 Partitioning blood components
• CPC Class Codes: G01N 33/569 for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

Integrated microfluidic devices comprising at least an enrichment channel (10) and a main electrophoretic flowpath (12) are provided. In the subject integrated devices, the enrichment channel and the main electrophoretic flowpath are positioned so that waste fluid flows away from said main electrophoretic flowpath through a discharge outlet (6). The subject devices find use in a variety of electrophoretic applications, including clinical assays, high throughput screening for genomics and pharmaceutical applications, point-or-care in vitro diagnostics, molecular genetic analysis and nucleic acid diagnostics, cell separations, and bioresearch generally.

Claims

1. An integrated microfluidic device comprising microchannels formed in a generally planar substrate, said device comprising:

an enrichment microchannel comprising an enrichment channel portion containing an enrichment medium, said enrichment channel portion having a sample inlet, a discharge outlet, an elution inlet, and an enriched fraction fluid outlet;

a main electrophoretic microchannel enclosing a main electrophoretic flowpath, said main electrophoretic microchannel being connected in fluid-conducting relation to said enriched fraction fluid outlet, and said electrophoretic microchannel comprising a detection region; and

means for moving a sample into said enrichment channel portion by way of said sample inlet and out from said enrichment channel portion by way of said discharge outlet, whereby at least a fraction of a component of interest in the sample is retained by said enrichment medium;

means for moving at least a portion of the fraction out from said enrichment channel portion by way of said enriched fraction outlet and into said main electrophoretic microchannel.

2. The device according to claim 1 wherein said means for moving the component of interest out from said enrichment channel portion and into said main electrophoretic microchannel comprises a first electrode located in said enrichment channel at a point upstream from said elution inlet and a second electrode located downstream from said detection region.

3. The device according to claim 1, further comprising a secondary microchannel connected in fluid-conducting relation between said enrichment fraction fluid outlet and said main electrophoretic microchannel.

4. The device according to claim 3 wherein said secondary microchannel encloses a secondary electrophoretic flowpath.

5. The device according to claim 3 wherein said secondary microchannel and said main electrophoretic microchannel intersect to form an injection cross.

6. An integrated microfluidic device comprising microchannels formed in a generally planar substrate, said device comprising:

an enrichment microchannel comprising an enrichment channel portion containing an enrichment medium, said enrichment channel portion having a first inlet and a first fluid outlet;

a main electrophoretic microchannel enclosing a main electrophoretic flowpath, said main electrophoretic microchannel being connected in fluid-conducting relation to said first fluid outlet, and said main electrophoretic microchannel comprising a detection region;

means for moving a sample into said enrichment channel portion by way of said first inlet and out from said enrichment channel portion by way of said first fluid outlet, whereby at least a fraction of a component of interest in the sample is retained by said enrichment medium,

a discharge channel connected in fluid communication with said first fluid outlet at a point upstream from said main electrophoretic flowpath, for discharging a portion of said sample other than said fraction away from said main electrophoretic flowpath; and

means for moving at least a portion of the fraction out from said enrichment channel portion by way of said first fluid outlet and into said main electrophoretic microchannel.

7. The device according to claim 6, further comprising a secondary microchannel connected in fluid conducting relation between said first fluid outlet and said main electrophoretic microchannel.

8. The device according to claim 7 wherein said secondary microchannel and said main electrophoretic microchannel intersect to form an injection cross.

9. An integrated microfluidic device comprising microchannels formed in a generally planar substrate, said device comprising:

an enrichment microchannel comprising an enrichment channel portion containing an enrichment medium, said enrichment channel portion having a first inlet and a first fluid outlet;

a main electrophoretic microchannel enclosing a main electrophoretic flowpath, said main electrophoretic microchannel being connected in fluid-conducting relation to said first fluid outlet, and said main electrophoretic microchannel comprising a detection region;

means for moving a sample into said enrichment channel portion by way of said first inlet and out from said enrichment channel portion by way of said first fluid outlet, whereby at least a fraction of a component of interest in the sample is retained by said enrichment medium;

a discharge channel connected in fluid communication with said first fluid outlet at a point upstream from said main electrophoretic flowpath, for discharging a portion of said sample other than said fraction away from said main electrophoretic flowpath;

means for moving at least a portion of the fraction out from said enrichment channel portion by way of said first fluid outlet and into said main electrophoretic microchannel; and

a plurality of input microchannels connected in fluid relation to said first inlet, said plurality of input microchannels comprising at least a sample input microchannel and an elution input microchannel.