Systems of sample processing having a macro-micro interface

• US 8,431,390 B2
• Filed: 11/02/2011
• Issued: 04/30/2013
• 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 Ioan
• Primary Examiner(s): Nguyen, Dave
• Assistant Examiner(s): BHAT, NARAYAN KAMESHWAR
• Application Number:
  US13/287,398
• Publication Number:
  US 20120088249A1
• Time in Patent Office: 545 Days
• Field of Search: 204/451, 422/68.1, 435/91.2, 435/173.9, 435/283.1, 435/6.11, 435/287.2, 435/288.6, 435/302.1, 536/25.4
• US Class Current: 435/287.2
• 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 nucleic acid sample processing and analysis system, comprising:

(a) an integrated set of modules comprising;

(i) a capturing and concentrating off-chip macroscale module comprising;

(1) a reservoir dimensioned to receive a liquid having an initial sample volume of a milliliter to a liter,

(2) magnetic beads contained in the macroscale module configured for capturing and concentrating a nucleic acid analyte from said initial sample volume; and

(ii) a bioprocessor module comprising;

(1) a microfluidic chip comprising a microfluidic channel in fluidic communication with the macroscale module and configured to receive the magnetic beads from said macroscale module, and

(2) a reaction chamber in fluid communication with the microfluidic channel, wherein the reaction chamber is configured to receive the nucleic acid analyte and for performing a nucleic acid amplification reaction on the nucleic acid analyte to produce a processed sample;

(b) a pressure source configured for moving the magnetic beads from the macroscale module into the microfluidic channel, wherein the magnetic beads with captured nucleic acid analyte move into the microfluidic chip in a reduced sample volume as compared to the initial sample volume;

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

(d) a magnet configured to immobilize the magnetic beads with the captured nucleic acid analyte in the macroscale module and to release the magnetic beads with the captured nucleic acid analyte into said reduced sample volume; and

(e) a computer comprising software programmed to fully automate processes performed by the off-chip macroscale module, the bioprocessor module, the pressure source, and the analysis module.

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 chip.

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

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 macroscale module.

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

8. The system of claim 1 wherein the nucleic acid analyte is DNA.

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

10. The system of claim 9 wherein the PCR reagents perform PCR on variable number tandem repeats (VNTR).

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

12. The system of claim 1 wherein the microfluidic chip is disposable.

13. The system of claim 1 wherein the microfluidic chip is sized to be hand-held.

14. The system of claim 1 wherein the nucleic acid analyte is RNA.

15. The system of claim 1 further comprising a cell lysis buffer.