MAGNETIC BIOLOGICAL ENTITY SEPARATION DEVICE AND METHOD OF USE

• US 20190270092A1
• Filed: 03/03/2018
• Published: 09/05/2019
• Est. Priority Date: 03/03/2018
• Status: Active Grant

• Current Assignee: Applied Cells Inc.
• Original Assignee: Yuchen Zhou
• Inventors: Zhou, Yuchen
• Granted Patent: US 10,449,553 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: B01D 21/283 Settling tanks provided with vibrators
• CPC Class Codes: B01D 35/06 Filters making use of electricity or magnetism ultrafiltration, microfiltration B01D61/14; electrodialysis, electro-osmosis B01D61/42; devices comprising filters and magnetic separators B03C1/30
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• 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 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0496 Travelling waves, e.g. in combination with electrical or acoustic forces
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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 1/005 : Pretreatment specially adapted for magnetic separation
• CPC Class Codes: B03C 1/01 : by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/0332 : using permanent magnets
• CPC Class Codes: B03C 1/23 : with material carried by oscillating fields; with material carried by travelling fields, e.g. generated by stationary magnetic coils; Eddy-current separators, e.g. sliding ramp
• CPC Class Codes: B03C 1/288 : disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 1/30 : Combinations with other devices, not otherwise provided for
• CPC Class Codes: B03C 2201/18 : Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/20 : Magnetic separation of bulk or dry particles in mixtures
• CPC Class Codes: B03C 2201/26 : for use in medical or biological applications
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: G01N 1/4077 : by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 15/00 : Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials identification of microorganisms C12Q
• 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 2015/1006 : for cytology
• CPC Class Codes: G01N 2015/1486 : Counting the particles
• CPC Class Codes: G01N 2035/00554 : using ultrasound
• CPC Class Codes: G01N 27/745 : for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01N 33/491 : by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: G01N 33/54333 : Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• 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

The current invention relates to the method and apparatus to magnetically separate biological entities with magnetic labels from a fluid sample. The claimed methods separate biological entities with magnetic labels by using a magnetic device. The claimed methods further include processes to dissociate biological entities magnetic conglomerate after magnetic separation.

Claims

1. A device for separating biological entities with magnetic labels from a fluid sample, the device comprising:

a first soft magnetic pole having a first base end contacting a first magnet, and a first tip end smaller than said first base end, thereby concentrating magnetic flux generated by said first magnet to said first tip end;

a second soft magnetic pole having a second base end contacting a second magnet, and a second tip end smaller than said second base end, thereby concentrating magnetic flux generated by said second magnet to said second tip end;

wherein said first and second tip ends being apart and across from each other to form magnetic field in between, whereas a first surface of said first tip end and a second surface of said second tip end converging into a convex;

a channel contacting said first and second surfaces by a third surface that conformally encompasses said convex; and

wherein said biological entities with magnetic labels are separated towards said convex from said fluid sample passing through said channel.

2. The device according to claim 1, wherein said first base end contacts north pole surface of said first magnet and said second base end contacts south pole surface of said second magnet.

3. The device according to claim 2, wherein a soft magnetic shield contacts south pole surface of said first magnet and north pole surface of said second magnet, thereby producing a magnetic flux path within said soft magnetic shield between said first and second magnets.

4. The device according to claim 1, wherein said first magnet is the same magnet as the said second magnet, wherein said first base end contacts north pole surface of said same magnet and said second base end contacts south pole surface of said same magnet.

5. The device according to claim 1, wherein said third surface of said channel maintains being conformal to said convex when said channel is separated from said convex.

6. The device according to claim 5, wherein said channel has a fourth surface opposite to said third surface around said channel, wherein wall of said channel has a first thickness at said fourth surface and a second thickness at said third surface, wherein said first thickness is larger than said second thickness.

7. The device according to claim 1, wherein said channel is a flexible channel whereas said third surface becomes non-conformal to said convex when said channel is separated from said convex.

8. The device according to claim 7, wherein a holder attaches to a fourth surface of said channel by a holder bottom surface, wherein said fourth surface being opposite to said third surface around said channel.

9. The device according to claim 8, wherein said holder forces said channel against said convex to cause said third surface of said channel to become conformal to said convex.

10. The device according to claim 7, wherein said holder bottom surface is substantially conformal to said convex.

11. The device according to claim 7, wherein a spacing between said holder bottom surface and said convex is any one of:

between 0 mm to 1 mm;

between 1 mm to 3 mm;

between two times of the wall thickness of said channel to three times of the wall thickness of the said channel; and

between three times of the wall thickness of said channel to five times of the wall thickness of said channel.

12. The device according to claim 1, wherein said first and second magnets are permanent magnets composed of at least one of:

Fe, Co, Ni, Ir, Mn, Nd, B, Sm, and Al.

13. The device according to claim 1, wherein said biological entities are bound with fluorescent labels.

14. The device according to claim 1, wherein said biological entities are any of:

cells, bacteria, particles, DNA, RNA, and molecules.

15. A method to separate biological entities with magnetic labels from a fluid sample comprising steps of:

passing said fluid sample through a channel positioned in contact with a separation magnet by a first surface of said channel;

said separation magnet separating said biological entities with magnetic labels from said fluid sample to form a magnetic conglomerate on internal surface of said channel opposing said first surface;

detaching said channel from said separation magnet and positioning said channel in contact with a second magnet by a second surface of said channel; and

said second magnet causing dissociation of said magnetic conglomerate.

16. The method according to claim 15, wherein said separation magnet comprises:

a first soft magnetic pole contacting a first magnet and concentrating magnetic flux from said first magnet to a first tip end of said first soft magnetic pole;

a second soft magnetic pole contacting a second magnet and concentrating magnetic flux from said second magnet to a second tip end of said second soft magnetic pole; and

wherein said first and second tip ends being apart and across from each other, with a third surface of said first tip end and a fourth surface of said second tip end converging into a convex; and

wherein said first surface of said channel contacting said third and fourth surface and conformally encompassing said convex.

17. The method according to claim 15, wherein said second surface is opposite to said first surface around said channel

18. A method to separate biological entities with magnetic labels from a fluid sample comprising steps of:

passing said fluid sample through a channel positioned in contact with a separation magnet by a first surface of said channel;

said separation magnet separating said biological entities with magnetic labels from said fluid sample to form a magnetic conglomerate on internal surface of said channel opposing said first surface;

detaching said channel from said separation magnet and positioning said channel in contact with a mechanical excitation means; and

said mechanical excitation means producing turbulence in said fluid sample contained in said channel and causing dissociation of said magnetic conglomerate.

19. The method according to claim 18, wherein said mechanical excitation means includes one of:

a motor producing vibration;

a piezoelectric element producing ultrasound vibration; and

a mechanical structure producing stretch, compression or twisting of said channel.

20. The method according to claim 18, wherein said channel is attached to a channel holder and said mechanical excitation means is in contact with said channel holder.