DEVICES AND METHODS FOR MANIPULATING COMPONENTS IN A FLUID SAMPLE

• US 20140120570A1
• Filed: 10/23/2013
• Published: 05/01/2014
• Est. Priority Date: 10/26/2012
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Yu, Liping, Warner, Brian David, Trotter, Joseph T.
• Granted Patent: US 8,956,536 B2
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• 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: B03C 1/02 acting directly on the substance being separated
• 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: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 1/4077 by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 15/02 Investigating particle size or size distribution by measuring osmotic pressure G01N7/10; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1425 using an analyser being characterised by its control arrangement
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2001/4038 electric methods, e.g. electromigration, electrophoresis, ionisation
• CPC Class Codes: G01N 2001/4094 : using ultrasound
• CPC Class Codes: G01N 2015/016 : White blood cells
• CPC Class Codes: G01N 2015/0288 : Sorting the particles
• CPC Class Codes: G01N 2015/1006 : for cytology
• CPC Class Codes: G01N 2015/142 : Acoustic or ultrasonic focussing
• CPC Class Codes: G01N 33/54326 : Magnetic particles

Abstract

Devices for sorting components (e.g., cells) contained in a liquid sample are provided. In certain aspects, the devices include a magnetic separation device and an acoustic concentrator device fluidically coupled to magnetic separation device. Aspects of the invention further include methods for sorting cells in a liquid sample, and systems, and kits for practicing the subject methods.

Claims

1. A fluidic device for manipulating components in a liquid sample, the device comprising:

a magnetic separator; and

an acoustic concentrator fluidically coupled to the magnetic separator.

2. The device according to claim 1, wherein the acoustic concentrator is fluidically coupled to an output of the magnetic separator.

3. The device according to claim 1, wherein the liquid sample has a viscosity of about 0.2 cP to about 1.5 cP.

4. The device according to claim 1, wherein the liquid sample comprises cells.

5. The device according to claim 1, wherein the device has an output flow rate of about 30 to 100 μ

L/min.

6. The device according to claim 1, wherein the magnetic separator comprises a permanent magnet.

7. The device according to claim 1, wherein the magnetic separator comprises a magnetic field guide.

8. The device according to claim 1, wherein the acoustic concentrator comprises a flow channel comprising an inlet and an outlet, the inlet and outlet defining a fluid flow path therebetween;

and

a vibration generator positioned adjacent to the fluid flow path and configured to produce an acoustic field in the fluid flow path.

9. The device according to claim 8, wherein the vibration generator is a piezoelectric transducer.

10. The device according to claim 9, wherein the vibration generator comprises lead zirconate titanate.

11. The device according to claim 1, comprising a processor configured to apply a magnetic field using the magnetic separator.

12. The device according to claim 1, comprising a processor configured to control the acoustic concentrator.

13. A flow cytometric system comprising:

a flow cytometric sample fluidic subsystem, the flow cytometric sample fluidic subsystem comprising;

a magnetic separator; and

an acoustic concentrator fluidically coupled to the magnetic separator; and

a flow cytometer fluidically coupled to the output of the flow cytometric sample fluidic subsystem.

14. A method of sorting a liquid sample, the method comprising:

separating magnetically labeled moieties from non-magnetically labeled moieties in the sample, thereby creating a first sorted sample; and

acoustically concentrating the first sorted sample to produce a second sorted sample.

15. The method according to claim 14, comprising collecting the second sorted sample.

16. The method according to claim 14, comprising analyzing the second sorted sample.

17. The method according to claim 16, wherein analyzing the second sorted sample comprises flow cytometric analysis.

18. The method according to claim 14, wherein the second sorted sample has an entrainment factor of about 0.0 to 1.0.

19. The method according to claim 14, further comprising labeling moieties in the liquid sample with a magnetic label.

20. The method according to claim 14, wherein the method is controlled by a processor.

21. The method according to claim 14, wherein the processor controls the method under a closed-loop feedback mechanism.

22. The method according to claim 14, wherein the liquid sample comprises a biological sample.

23. The method according to claim 14, wherein the liquid sample is obtained from a human.

24. A kit comprising:

a wash solution for washing a magnetic separator; and

a magnetic label for labeling moieties in a liquid sample.