Magnetic cell isolation techniques

Patent metadata

Field	Value
Publication number	US-10696961-B2
Application number	US-201715829615-A
Country	US
Kind code	B2
Filing date	Dec 1, 2017
Priority date	Dec 1, 2017
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

Provided are techniques that may include a disposable magnetic cell isolation holder having one or more passages that accommodate a magnetic retention material to facilitate magnetic cell isolation without adjustment of magnetic field parameters between isolation procedures using different magnetic particle sizes. When the magnetic cell isolation holder is coupled to a magnetic field generator, a first passage corresponding to a smaller particle size is positioned in a magnetic field where the magnetic field characteristics are different relative to a second passage, of a second holder or in the same holder, for use with another bead size.

First claim

The invention claimed is:

1. A system, comprising:
a magnetic field generator configured to generate a magnetic field;
a first holder configured to be removably coupled to the magnetic field generator, the first holder comprising a first passage configured to be positioned within the magnetic field at a first location when the first holder is coupled to the magnetic field generator; and
a second holder configured to be removably coupled to the magnetic field generator, the second holder comprising a second passage configured to be positioned within the magnetic field at a second location when the second holder is coupled to the magnetic field generator,
wherein:
the first passage experiences a first magnetic field strength and a first magnetic field gradient, within the magnetic field at the first location; and
the second passage experiences a second magnetic field strength and a second magnetic field gradient, within the magnetic at the second location, and wherein the second magnetic field strength is different than the first magnetic field strength or the second magnetic field gradient is different than the first magnetic field gradient, or a combination thereof.

2. The system of claim 1 , wherein the magnetic field generator is coupled to a frame, the frame conducting magnetic flux and forming a receiving area configured to receive the first holder or the second holder.

3. The system of claim 2 , wherein the receiving area is sized to receive only one of the first holder or the second holder at a given time.

4. The system of claim 2 , wherein the receiving area is configured to receive only a portion of the first holder or the second holder.

5. The system of claim 4 , wherein the portion comprises the first passage of the first holder or the second passage of the second holder.

6. The system of claim 2 , wherein the frame comprises a retractable portion that reduces the magnetic flux generated by the magnetic field generator from going beyond the receiving area while the first holder is uncoupled to the magnetic field generator.

7. The system of claim 6 , wherein the retractable portion comprises a spring that compresses to allow the first holder to enter the receiving area of the frame.

8. The system of claim 1 , wherein, when the first holder is not coupled to the magnetic field generator, the first passage does not experience the first magnetic field strength.

9. The system of claim 2 , wherein the first holder comprises a first end surface configured to abut a stopping portion of the frame when the first holder is coupled to the magnetic field generator.

10. The system of claim 9 , wherein the second holder comprises a second end surface configured to abut the stopping portion of the frame when the second holder is coupled to the magnetic field generator, and wherein a first distance between the first end surface and the first passage is different than a second distance between the second end surface and the second passage.

11. The system of claim 1 , wherein a first passage and the second passage are different sizes.

12. The system of claim 1 , wherein the first holder is configured to be fluidically coupled to a first source of a first size bead, and wherein the second holder is configured to be fluidically coupled to a second source of a second size bead.

13. The system of claim 12 , wherein a diameter of the first size bead is less than 1 μm and a diameter of the second size bead greater than 2 μm.

14. The system of claim 12 , wherein the first size bead is bound to a target cell within a first cell mixture and the second size bead is bound to a target cell within a second cell mixture.

15. The system of claim 1 , wherein the first passage or the second passage comprises a magnetic intensifier.

16. A system, comprising:
a first kit comprising:
a plurality of first size beads; and
a first holder comprising a first passage configured to receive the plurality of first size beads, the first passage positioned within the first holder such that, when the first holder is removably coupled to a magnetic field generator generating a magnetic field, the first holder is positioned within the magnetic field at a first location; and
a second kit comprising:
a plurality of second size beads; and
a second holder comprising a second passage configured to receive the plurality of second size beads, the second passage positioned within the second holder such that, when the second holder is removably coupled to the magnetic field generator generating the magnetic field, the second holder is positioned within the magnetic field at a second location different than the first location;
wherein:
the first passage experiences a first magnetic field strength and a first magnetic field gradient within the magnetic field at the first location; and
the second passage experiences a second magnetic field strength and a second magnetic field gradient within the magnetic field at the second location, and wherein the second magnetic field strength is different than the first magnetic field strength or the second magnetic field gradient is different than the first magnetic field gradient, or a combination thereof.

17. A method for isolating target cells, comprising:
positioning a first holder having a first passage within a receiving area of a frame coupled to a magnetic field generator;
generating a first magnetic field in the receiving area by the magnetic field generator when the first holder is coupled to the magnetic field generator to cause the first passage to experience a first magnetic field strength, a first magnetic field gradient, or both;
positioning a second holder having a second passage within the receiving area, wherein the first passage and the second passage are positioned at different locations within the receiving area; and
generating a second magnetic field in the receiving area by the magnetic field generator when the second holder is coupled to the magnetic field generator to cause the second passage to experience a second magnetic field strength, a second magnetic field gradient, or both.

18. The method of claim 17 , wherein the first magnetic field and the second magnetic field are generated from the magnetic field generated by the magnetic field generator.

19. The method of claim 17 , wherein, when the first holder is positioned within the receiving area of the frame, the second holder is not positioned within the receiving area of the frame, and when the second holder is positioned within the receiving area of the frame, the first holder is not positioned within the receiving area of the frame.

20. The method of claim 17 , further comprising:
incubating a first cell mixture with a first size bead and a second cell mixture with a second size bead such that a target cell in the first cell mixture is labelled with the first size bead and a target cell in the second cell mixture is labelled with the second size bead; and
passing the first cell mixture through the first passage and the second cell mixture through the second passage.

Assignees

• Gen Electric
• Global Life Sciences Solutions Usa Llc

Inventors

• Zhang Xiaohua
• Mine Susumu
• Bai Ye
• Smith Reginald
• Xu Minfeng
• Griffin Weston
• Conway Kenneth

Classifications

• B03C1/288 Primary

  disposed at the outer circumference of a recipient · CPC title

• B03C1/01

  by addition of magnetic adjuvants · CPC title

• C12M33/00

  Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus (chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00) · CPC title

• C12M45/02

  by mechanical forces; Stirring; Trituration; Comminuting (crushing, pulverizing, disintegrating in general B02C) · CPC title

• C12M47/04

  Cell isolation or sorting (purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04) · CPC title