Integrated heater and magnetic separator

• US 9,618,139 B2
• Filed: 07/23/2008
• Issued: 04/11/2017
• Est. Priority Date: 07/13/2007
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan
• Primary Examiner(s): HURST, JONATHAN M
• Application Number:
  US12/178,586
• Publication Number:
  US 20090134069A1
• Time in Patent Office: 3,184 Days
• Field of Search: 422101, 210222
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2200/148 Specific details about calibrations
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1861 using radiation
• 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 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: B03C 1/06 with magnets moving during operation
• CPC Class Codes: B03C 1/12 with magnets moving during operation; with movable pole pieces
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: F16K 2099/0084 Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0001 Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/003 Valves for single use only
• CPC Class Codes: F16K 99/0032 using phase transition or influencing viscosity
• CPC Class Codes: F16K 99/0044 using thermo-electric means
• CPC Class Codes: F16K 99/0061 : actuated by an expanding gas or liquid volume
• CPC Class Codes: G01N 2035/00881 : network configurations
• 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

An apparatus for providing thermal and magnetic energy to a receptacle containing a reaction mixture and a magnetic retention member. The apparatus can also control heating of a reaction mixture, and bring about a separation of magnetic particles from the reaction mixture. The reaction mixture typically comprises polynucleotides from a biological sample that are being brought into a PCR-ready form.

Claims

1. A system for extraction of nucleic acids comprising an integrated separator and heater and a rack removably received in the system, the system comprising:

a heater assembly, wherein the heater assembly comprises a plurality of independently controllable heater units aligned collinearly along a horizontal first axis, each of which is configured to accept and to heat a single process tube of a plurality of process tubes placed in the heater assembly;

one or more magnets affixed to a supporting member, wherein all of the one or more magnets in the system are disposed on a front side of the plurality of independently controllable heater units and aligned along a second axis parallel to the first axis;

a rack removably received in the system, at least a portion of the rack removably received on a back side of the plurality of independently controllable heater units opposite the one or more magnets on the front side;

a plurality of holders, each holder comprising a single process tube of the plurality of process tubes, the plurality of holders removably received in the rack such that a portion of each process tube is received in a single heater unit of the plurality of independently controllable heater units as the rack is inserted into the system;

a motorized mechanism configured to move the supporting member in such a manner that all of the one or more magnets move uniformly backwards and forwards together in a vertical direction perpendicular to the second axis, and during at least a portion of the motion all of the one or more magnets simultaneously maintain proximity to an exterior side of each of the process tubes in the heater assembly sufficient to move magnetic particles contained in the process tubes against a wall of the process tubes; and

control circuitry to control the motorized mechanism and to control heating of the heater units.

2. The integrated heater and separator of claim 1, wherein both the heating of the plurality of process tubes and the separation of magnetic particles within the process tubes occur when the process tubes are situated in the heater units, and without requiring the process tubes to be removed or repositioned after the heating.

3. The integrated magnetic separator and heater of claim 2, wherein each of the heater units comprises a power resistor.

4. The integrated heater and separator of claim 1, wherein each heater unit comprises a heat block having an internal cavity configured to partially surround a lower portion of one of the plurality of process tubes on at least two sides.

5. The integrated heater and separator of claim 4, wherein each heater unit is comprised of an open face on at least one side and each of the one or more magnets face an open face of the heater unit when the magnet is in close proximity to the process tube.

6. The integrated heater and separator of claim 1, wherein each heater unit comprises a heat block, wherein the heat block is made of a material selected from:

aluminum;

silver;

gold;

copper; and

alloys thereof.

7. The integrated heater and separator of claim 1, configured to heat a 1 ml biological sample in one of the process tubes from room temperature to 65°

C. in less than 3 minutes.

8. The integrated heater and separator of claim 1, wherein the heater assembly further comprises one or more temperature sensors configured to sense and record the respective temperatures of each of the heat blocks.

9. The integrated heater and separator of claim 1, wherein the motorized mechanism comprises a shaft to which the supporting member is attached, and a motor configured to move the supporting member along the shaft.

10. The integrated heater and separator of claim 9, wherein the supporting member is configured to move between a first position, situated away from the plurality of process tubes, and a second position situated in close proximity to the plurality of process tubes, and is further configured to move at an amplitude about the second position where the amplitude is smaller than a distance between the first position and the second position as measured along the shaft.

11. The integrated separator and heater of claim 1, wherein there are 12 heater units.

12. The integrated separator and heater of claim 4, wherein the heat block comprises two sides perpendicular to each other.

13. The integrated separator and heater of claim 4, wherein the heat block surrounds the lower portion of the process tube on two sides.

14. The integrated separator and heater of claim 4, wherein the heat block surrounds the lower portion of the process tube on three sides.

15. The integrated separator and heater of claim 1, wherein each of the process tubes comes within 1 mm to at most only one magnet.

16. A diagnostic apparatus comprising the integrated separator and heater of claim 1.