MICROFLUIDIC DEVICES

• US 20120088249A1
• Filed: 11/02/2011
• Published: 04/12/2012
• Est. Priority Date: 09/15/2004
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Jovanovich, Stevan Bogdan, Blaga, Iuliu I.
• Granted Patent: US 8,431,390 B2
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• 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 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0806 Standardised forms, e.g. compact disc [CD] format
• 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 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1844 : using fans
• CPC Class Codes: B01L 2400/0409 : centrifugal forces
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0638 : membrane valves, flap valves
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/086 : using baffles or other fixed flow obstructions
• 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 3/502761 : 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: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: G01N 1/34 : Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 27/44721 : by optical means
• 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 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C

Abstract

Methods and devices for the interfacing of microchips to various types of modules are disclosed. The technology disclosed can be used as sample preparation and analysis systems for various applications, such as DNA sequencing and genotyping, proteomics, pathogen detection, diagnostics and biodefense.

Claims

1. A system, comprising:

(a) a macroscale module that receives a liquid solution sample volume comprising a target analyte and that comprises beads for capturing and concentrating the target analyte;

(b) a bioprocessor module comprising;

(i) a microfluidic device comprising a microfluidic channel in fluidic communication with the macroscale module and configured to receive the beads, and

(ii) a reaction chamber for performing a reaction on the target analyte to produce a processed sample;

(c) a pressure source for moving the beads from the macroscale chamber into the microfluidic channel, wherein moving the beads with captured analyte into the microfluidic device effects a downscaling of the sample volume; and

(d) an analysis module fluidically connected to said reaction chamber and configured to perform an analysis on the processed sample.

2. The system of claim 1 wherein the pressure source comprises a pump.

3. The system of claim 2 wherein the pump comprises a pneumatic diaphragm pump located on the microfluidic device.

4. The system of claim 1 wherein the analyte is concentrated at least 1000-fold from the sample volume.

5. The system of claim 1 configured to process a plurality of samples.

6. The system of claim 1 wherein the system is configured to lyse cells in the liquid solution sample volume.

7. The system of claim 1 wherein the beads bind DNA.

8. The system of claim 7 wherein the beads are magnetic beads.

10. The system of claim 1 wherein the target analyte is DNA.

11. The system of claim 1 wherein the system further comprises PCR reagents.

12. The system of claim 11 wherein the PCR reagents perform PCR on variable number tandem repeats (VNTR).

13. The system of claim 1 wherein the analysis module is configured to perform capillary electrophoresis.

14. The system of claim 1 wherein:

(i) the target analyte is DNA;

(ii) the beads are magnetic beads that bind DNA;

(iii) the reaction chamber comprises PCR reagents; and

(iv) analysis module is configured to perform capillary electrophoresis.

9. The system of claim 9 further comprising a magnet positioned to immobilize the beads.

15. A method comprising:

(a) in a macroscale module, capturing a target analyte from a liquid solution sample volume with beads;

(b) removing the liquid solution from the beads with captured target analyte;

(c) moving the beads with captured target analyte with a pressure source from the macroscale module into a microfluidic channel on a microfluidic device in fluid communication therewith, wherein moving the beads with captured analyte into the microfluidic device effects a downscaling of the sample volume;

(d) moving the beads with captured target analyte from the microfluidic channel into a reaction chamber in fluid communication therewith;

(e) performing a reaction a reaction on the analyte in the reaction chamber to produce a processed sample;

(f) moving the reaction product from the reaction chamber into an analysis module in fluidic communication therewith; and

(g) performing an analysis on the processed sample.

16. The method of claim 15 wherein the pressure source comprises a pump.

17. The method of claim 15 wherein the pump comprises a pneumatic diaphragm pump located on the microfluidic device.

18. The method of claim 15 wherein the analyte is concentrated at least 1000-fold from the sample volume.

19. The method of claim 15 wherein to process a plurality of samples.

20. The method of claim 15 wherein the method is configured to lyse cells in the liquid solution sample volume.

21. The method of claim 15 wherein the beads bind DNA.

22. The method of claim 15 wherein the beads are magnetic beads.

23. The method of claim 22 comprising immobiling the beads in the macrofluidic module with a magnet.

24. The method of claim 15 wherein the target analyte is DNA.

25. The method of claim 15 wherein the target analyte is DNA and the reaction comprises performing PCR on the DNA.

26. The method of claim 25 wherein PCR is performed on variable number tandem repeats (VNTR).

27. The method of claim 15 comprising performing capillary electrophoresis on the processed sample in the analysis module.

28. The method of claim 15 wherein:

(i) the target analyte is DNA;

(ii) the beads are magnetic beads that bind DNA;

(iii) the reaction comprises performing PCR; and

(iv) the analysis comprises performing capillary electrophoresis.