Magnetic separation of rare cells

• US 9,217,131 B2
• Filed: 01/20/2011
• Issued: 12/22/2015
• Est. Priority Date: 01/21/2010
• Status: Active Grant

• Current Assignee: BioCEP Ltd.
• Original Assignee: BioCEP Ltd.
• Inventors: Lamish, Aharon, Klein, Ofer
• Primary Examiner(s): KWAK, DEAN P
• Application Number:
  US13/574,557
• Publication Number:
  US 20120295302A1
• Time in Patent Office: 1,797 Days
• Field of Search: 422/73
• US Class Current: 1/1
• CPC Class Codes: B03C 1/0335 using coils
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/26 for use in medical or biological applications
• CPC Class Codes: C12M 47/02 Separating microorganisms from the culture medium; Concentration of biomass separating microorganisms from their culture media C12N1/02
• CPC Class Codes: C12N 1/02 Separating microorganisms from their culture media
• CPC Class Codes: C12Q 1/24 Methods of sampling, or inoculating or spreading a sample; Methods of physically isolating an intact microorganisms

Abstract

A magnetic separation system configured to separate with high qualitative and quantitative yield magnetized cells from cell mixtures, comprising at least one electromagnet structured to generate a magnetic field flux about a plurality of separation and sufficient to attract a majority of the magnetized cells in the mixture, and a pump to drive the cell mixture at a controlled flow rate through a tube disposed within the thereby separating a majority of the magnetized cells from the mixture. The system is particularly useful to retrieve rare cells from a fluid mixture of cells having low abundance of the rare cells relative to the rest of the cells while sustaining viability of the cells.

Claims

1. A magnetic separation system comprising:

a sample container;

a first pump disposed downstream from said sample container;

a carrier container;

a second pump disposed downstream from said carrier container;

a mixture container disposed downstream from said first and second pumps;

a plurality of electromagnets;

a tube extending from said mixture container, passing about said plurality of electromagnets, and terminating at a plurality of collection vessels;

a third pump associated with said tube;

a processor or a computer; and

a computer-readable medium having stored thereon one or more programs that, when executed by said processor or said computer;

operate said first and second pumps to separately feed, into said mixture container, a sample fluid from said sample container and a carrier fluid from said carrier container, wherein the sample fluid comprises magnetized cells and non-magnetized cells, operate said plurality of electromagnets to generate magnetic flux, and at the same time operate said third pump to cause a mixture of the sample fluid and the carrier fluid to flow inside said tube about said plurality of electromagnets, such that;

(i) a majority of the magnetized cells are attracted to a wall of said tube, about said plurality of electromagnets, and

(ii) a majority of the non-magnetized cells are drained to a first collection vessel of said plurality of collection vessels,

operate said plurality of electromagnets to terminate the magnetic flux, and at the same time operate said second and third pumps to feed a washing fluid from said carrier container, through said mixture container and into said tube, such that attracted magnetized cells are dislodged from the wall of said tube and are washed, with the washing fluid, to a second collection vessel of said plurality of collections vessels.

2. The system according to claim 1, wherein the one or more programs, when executed by said processor or said computer, cause the system to sustain the viability of the cells by generating the magnetic flux while avoiding heat dissipation detrimental to the vitality of the cells.

3. The system according to claim 1, wherein the tube is disposed generally horizontally about the plurality of electromagnets.

4. The system according to claim 1, wherein the plurality of electromagnets is arranged about a generally horizontal plane for disposing the tube generally horizontally about the plurality of electromagnets.

5. The system according to claim 1, wherein the tube is disposed generally vertically about the plurality of electromagnets.

6. The system according to claim 1, wherein the plurality of electromagnets is arranged about a generally vertical plane for disposing the tube generally horizontally about the plurality of electromagnets.

7. The system according to claim 1, wherein an electromagnet is configured to generate a magnetic flux about two zones.

8. The system according to claim 1, wherein the tube is disposed about the plurality of electromagnets in a successive manner, such that each successive electromagnet of the plurality of electromagnets attracts onto the wall of the tube a majority of the magnetized cells remaining in the flowing mixture following attraction by a preceding electromagnet of the plurality of electromagnets.

9. The system according to claim 1, further comprising at least one mechanism configured to promote the dislodging of attracted magnetized cells from the wall of said tube,

wherein the one or more programs, when executed by said processor or said computer, further operate said at least one mechanism to promote the dislodging of attracted magnetized cells from the wall of said tube.

10. The system according to claim 9, wherein the one or more programs, when executed by said processor or said computer, further operate said at least one mechanism to degauss the plurality of electromagnets.

11. The system according to claim 9, wherein the mechanism comprises an configured to flow an air bubble in the washing fluid inside the tube, and

wherein the one or more programs, when executed by said processor or said computer, operate said and said third pump to cause the air bubble to flow in the washing fluid inside the tube.

12. The system according to claim 9, wherein the mechanism comprises an to vibrate the tube,

and wherein the one or more programs, when executed by said processor or said computer, operate said to vibrate the tube.