Integrated heater and magnetic separator

• US 10,139,012 B2
• Filed: 04/07/2017
• Issued: 11/27/2018
• 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:
  US15/482,572
• Publication Number:
  US 20180017184A1
• Time in Patent Office: 599 Days
• 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 method of extracting nucleic acids using a rack and an integrated separator and heater, the integrated separator and heater comprising a plurality of heater units aligned collinearly along a horizontal first axis, the integrated separator and heater further comprising one or more magnets disposed on a first side of the plurality of heater units and aligned along a second axis parallel to the first axis, the method comprising:

inserting a plurality of holders in the rack, each holder comprising a single process tube of a plurality of process tubes;

inserting the rack into the integrated separator and heater such that at least a portion of rack is removably received on a second side of the plurality of heater units opposite the one or more magnets on the first side, wherein a portion of each process tube of the plurality of process tubes is received in a single heater unit of the plurality of heater units when the rack is inserted into the integrated separator and heater;

moving all of the one or more magnets backwards and forwards together in a vertical direction perpendicular to the second axis while maintaining proximity to an exterior side of each of the process tubes received in the integrated separator and heater;

during at least a portion of the motion, moving magnetic particles contained in the process tubes; and

independently controlling each heater unit of the plurality of heater units to apply heat to the plurality of process tubes received in the integrated separator and heater.

2. The method of claim 1, wherein all of the one or more magnets are moved and the plurality of process tubes are heated at the same time.

3. The method of claim 1, wherein each heater unit comprises a cavity configured to partially surround a portion of the process tube received in the cavity.

4. The method of claim 3, wherein the cavity surrounds a lower portion of the process tube on two sides when the rack is inserted into the integrated separator and heater.

5. The method of claim 3, wherein the cavity surrounds a lower portion of the process tube on three sides when the rack is inserted into the integrated separator and heater.

6. The method of claim 3, further comprising sensing a temperature of each cavity.

7. The method of claim 1, wherein the one or more magnets are affixed to a supporting member, and wherein moving all of the one or more magnets comprising moving the supporting member.

8. The method of claim 7, wherein the supporting member is affixed to a shaft, and wherein moving all of the one or more magnets comprises moving the supporting member along the shaft.

9. The method of claim 8, further comprising moving the supporting member 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.

10. The method of claim 9, further comprising moving the supporting member 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 method of claim 1, wherein the integrated separator and heater comprises 12 heater units.

12. The method of claim 1, wherein 12 holders are inserted in the rack.

13. The method of claim 1, wherein applying heat to the plurality of process tubes received in the integrated separator and heater comprises raising the temperature of a 1 ml sample in one of the process tubes from room temperature to about 65°

C. in less than 3 minutes.

14. The method of claim 1, wherein moving the magnetic particles comprising moving the magnetic particles against a wall of the process tubes.

15. The method of claim 1, wherein moving the magnetic particles comprising concentrating the magnetic particles in a portion of the process tubes.

16. The method of claim 1, wherein moving the magnetic particles comprises sliding the magnetic particles toward the bottom of the process tubes.

17. The method of claim 1, wherein the magnetic particles are in suspension in solution in the process tubes, and wherein moving the magnetic particles comprises collecting the suspended magnetic particles into one location inside the process tubes.

18. The method of claim 17, further comprising aspirating the solution from the process tubes after collecting the suspended magnetic particles.