Microfluidic devices

• US 7,745,207 B2
• Filed: 02/02/2007
• Issued: 06/29/2010
• Est. Priority Date: 02/03/2006
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Jovanovich, Stevan B., Blaga, Iuliu I.
• Primary Examiner(s): Forman; BJ
• Assistant Examiner(s): BHAT, NARAYAN KAMESHWAR
• Application Number:
  US11/670,866
• Publication Number:
  US 20080014576A1
• Time in Patent Office: 1,243 Days
• Field of Search: 135/283.1, 135/288.5, 422/100
• US Class Current: 435/288.5
• 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: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• 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 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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 3/5025 : for parallel transport of multiple samples
• 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 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: C12N 15/1003 : Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
• CPC Class Codes: C12N 15/1013 : by using magnetic beads
• CPC Class Codes: C12Q 1/24 : Methods of sampling, or inoculating or spreading a sample; Methods of physically isolating an intact microorganisms
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 1/6869 : Methods for sequencing
• CPC Class Codes: C12Q 1/70 : involving virus or bacteriophage immunoassay for viruses G01N33/56983
• CPC Class Codes: G01N 2035/00514 : Stationary mixing elements
• CPC Class Codes: Y10T 436/163333 : Organic [e.g., chemical warfare agents, insecticides, etc.]
• CPC Class Codes: Y10T 436/25875 : Gaseous sample or with change of physical state

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 method of mixing solutions comprising:

a) providing a microfluidic device comprising;

(i) a first microfluidic channel comprising a first pump and a first solution;

(ii) a second microfluidic channel comprising a second, opposing pump and a second solution; and

(iii) a third microfluidic channel,

wherein each pump comprises an inlet valve, a pump valve and an outlet valve, and the first, second and third channels intersect at a common junction that is not a valve; and

b) performing a pumping cycle comprising;

(i) opening the inlet valves and closing the outlet valves;

(ii) opening the pump valves, wherein the first and second solutions are pumped into the pump valves;

(iii) closing the inlet valves and opening the outlet valves; and

(iv) closing the pump valves, wherein the solutions in the pump valves are pumped into the third channel in laminar flow and wherein opening the outlet valves and closing the pump valves results in back and forth movement of the solutions, wherein the solutions are mixed.

2. The method of claim 1 wherein the structure is comprised on a microchip.

3. The method of claim 1 wherein the first channel is connected to a port that holds the first solution and the second channel is connected to a port that holds the second solution.

4. The method of claim 1 wherein the first solution comprises an analyte and the second fluid comprises a reagent.

5. The method of claim 1 further comprising repeating step (b).

6. The method of claim 1 wherein the third channel comprises a serpentine area.

7. The method of any of claims 1-6 wherein the microfluidic device comprises a fluidic layer, a deformable membrane layer and a pneumatic layer, wherein each valve in the device comprises the deformable membrane layer sitting against a valve seat in the fluidic layer to close a fluidic path between microfluidic channels in the fluidic layer, and the pneumatic layer comprises a pneumatic displacement chamber opposite the membrane and connected to a vacuum or pressure source and wherein applying vacuum or pressure to the membrane layer deforms the deformable membrane, thereby opening or closing the valve.

8. The method of claim 7 wherein the pneumatic displacement chamber is connected to a vacuum source and wherein applying vacuum to the membrane layer deforms the deformable membrane, thereby opening the valve.

9. The method of claim 7 wherein the valves comprise vias in the fluidic layer.

10. The method of claim 7 wherein the fluidic layer and the actuation layer comprise glass wafers into which channels are etched.

11. A method of mixing solutions comprising:

a) providing a microfluidic device comprising a router comprising;

(i) a first microfluidic channel comprising a first valve and a first port comprising a first solution;

(ii) a second microfluidic channel comprising a second valve and a second port comprising a gas;

(iii) a third microfluidic channel comprising a third valve and a third port comprising a second solution;

(iv) a fourth microfluidic channel comprising a fourth valve; and

(v) a reaction chamber

wherein the first, second, third and fourth channels connect to a central diaphragm valve and the fourth channel connects with the reaction chamber;

b) pumping the first and second solutions from the first and third ports and air from the second port into the reaction chamber to form boluses separated by air, wherein mixing of the solutions is aided by the back and forth movement of the two solutions into the second channel during multiple pumping steps.

12. The method of claim 11 wherein the microfluidic device is comprised on a microchip.

13. The method of claim 11 wherein the first solution comprises an analyte and the second solution comprises a reagent.

14. The method of claim 11 wherein the gas is air.

15. The method of any of claims 11, 12, 13 and 14 wherein the microfluidic device comprises a fluidic layer, a deformable membrane layer and a pneumatic layer, wherein each valve in the device comprises the deformable membrane layer sitting against a valve seat in the fluidic layer to close a fluidic path between microfluidic channels in the fluidic layer, and the pneumatic layer comprises a pneumatic displacement chamber opposite the membrane and connected to a vacuum or pressure source and wherein applying vacuum or pressure to the membrane layer deforms the deformable membrane, thereby opening or closing the valve.

16. The method of claim 15 wherein the pneumatic displacement chamber is connected to a vacuum source and wherein applying vacuum to the membrane layer deforms the deformable membrane, thereby opening the valve.

17. The method of claim 15 wherein the valves comprise vias in the fluidic layer.

18. The method of claim 15 wherein the fluidic layer and the actuation layer comprise glass wafers into which channels are etched.