DEVICE FOR CAPTURE OF PARTICLES IN A FLOW

• US 20160061811A1
• Filed: 04/11/2014
• Published: 03/03/2016
• Est. Priority Date: 04/11/2013
• Status: Active Grant

• Current Assignee: The Governing Council of the University of Toronto (University of Toronto)
• Original Assignee: The Governing Council of the University of Toronto (University of Toronto)
• Inventors: SARGENT, Edward Hartley, KELLEY, Shana Olwyn, MOHAMADI, Mohamad Reza
• Granted Patent: US 10,073,079 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• 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 1/01 by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/0335 using coils
• CPC Class Codes: B03C 1/034 characterised by the matrix elements
• 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 2201/26 for use in medical applications
• 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 15/01 specially adapted for biological cells, e.g. blood cells investigating sedimentation of particle suspensions in blood G01N15/05
• CPC Class Codes: G01N 15/0606 by collecting particles on a support
• CPC Class Codes: G01N 15/0656 : using electric, e.g. electrostatic methods or magnetic methods by investigating individual particles G01N15/1031, G01N15/12
• CPC Class Codes: G01N 2015/0053 : in liquids, e.g. trouble
• CPC Class Codes: G01N 27/00 : Investigating or analysing materials by the use of electric, electrochemical, or magnetic means G01N3/00 – G01N25/00 take precedence; measurement or testing of electric or magnetic variables or of electric or magnetic properties of materials G01R
• 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 33/57434 : of prostate

Abstract

Devices and methods for capture of target particles in a flow. There is a plurality of flow rate-reducing structures in a flow chamber, each structure including a trapping surface shaped to reduce flow rate in a vicinity of the trapping surface. Reduced flow rate in the vicinity of the trapping surface is non-zero and has a magnitude lower than that of flow rate in other regions of the flow chamber. The reduced flow rate is sufficiently low for an attraction force acting on the target particles to overcome drag force on the target particles, to promote capture of particles in the vicinity of the trapping surface. The device may exhibit different sorting zones for capturing particles that experience different amounts and/or types of attraction force. The device may enable sorting of cells according to their level of display of specific protein surface markers.

Claims

1. A device for capture of target particles in a flow, the device comprising:

a flow chamber in fluid communication with a flow inlet and a flow outlet; and

a plurality of flow rate-reducing structures in the flow chamber, each structure comprising a trapping surface shaped to reduce flow rate in a vicinity of the trapping surface;

wherein reduced flow rate in the vicinity of the trapping surface is non-zero and has a magnitude lower than that of flow rate in other regions of the flow chamber; and

wherein the reduced flow rate is sufficiently low for an attraction force acting on the target particles to overcome drag force on the target particles, to promote capture of particles in the vicinity of the trapping surface.

2. The device of claim 1 wherein the attraction force is a magnetic force.

3. The device of claim 2, further comprising at least one magnet for generating the magnetic force.

4. The device of claim 3, wherein there is a plurality of magnets arranged in pairs of opposing polarity, one half of each pair being arranged in a first array and a remaining half of each pair being arranged in a corresponding second array, the flow chamber being positioned between the first and second arrays.

5. The device of claim 3 wherein the at least one magnet is configured to generate a magnetic field gradient over the flow chamber.

6. The device of claim 1, wherein the trapping surface of at least one flow rate-reducing structure includes at least one concave surface, the concave surface being concave towards a direction of flow from the inlet to the outlet.

7. The device of claim 1, wherein the trapping surface of at least one flow rate-reducing structure is defined by two joined arms defining an angle.

8. The device of claim 1, wherein the flow rate-reducing structures comprise at least one X-shaped structure or cross-shaped structure, wherein the trapping surface is defined by two arms of the X-shaped or cross-shaped structure.

9. The device of claim 1, wherein the structures are regularly spaced in the flow chamber.

10. The device of claim 1, wherein the structures are arranged in a plurality of rows substantially perpendicular to the direction of flow, the rows being staggered with respect to each other.

11. The device of claim 1, wherein a plurality of sorting portions are defined in the flow chamber, each sorting portion including a respective plurality of flow rate-reducing structures, wherein each sorting portion promotes capture of respective different target particles experiencing respective different amounts and/or types of attraction force.

12. The device of claim 11 wherein each sorting portion has a different respective reduced flow rate.

13. The device of claim 12 wherein each sorting portion has a different respective average flow rate.

14. The device of claim 11 wherein the sorting portions are defined as discrete compartments in fluid communication with each other.

15. A method for capturing target particles in a sample, the method comprising:

introducing the sample containing the target particles to the device of claim 1, the target particles being susceptible to a magnetic attraction force;

applying a magnetic field to the flow chamber while flowing the sample through the flow chamber, the magnetic field having a gradient over the flow chamber;

removing the magnetic field; and

eluting the target particles captured in the flow chamber.

16. The method of claim 15, wherein the target particles are labeled with magnetically susceptible nanobeads.

17. The method of claim 15, wherein the device is the device of claim 11, wherein the target particles include particles having different magnetic properties and each sorting portion promotes capture of respective different particles according to respective different amounts of magnetic attraction force experienced by the respective different particles.

18. The method of claim 17, wherein the particles include magnetically labeled cancer cells in a patient sample.

19. The method of claim 17, wherein the target particles are labeled with magnetically susceptible nanobeads, and wherein each sorting portion promotes capture of respective different particles based on the number of magnetically susceptible nanobeads bonded to the respective different particles.

20. A system for detecting target particles in a sample, the system comprising:

the device of claim 1, referred to as a capture device; and

a detection device comprising sensing electrodes;

wherein the sensing electrodes generate an electrical signal in response to contact of the target particles with the sensing electrodes.

21. The system of claim 20 wherein the sensing electrodes comprise a sensing surface including an electrical or electrochemical reporter system targeted towards the target particles.

22. The system of claim 21 wherein the sensing electrodes are nanostructured microelectrodes (NMEs) comprising surface groups complementary to the target particles.

23. The system of claim 22 wherein the surface groups complementary to the target particles include antibodies complementary to one or more target proteins.

24. The system of claim 23 wherein the one or more target proteins include one or more cancer-specific proteins.

25. The system of claim 20 wherein the system is provided as a single integrated chip.

26. The system of claim 20 wherein the capture device and the sensing device are in fluid communication with each other, for facilitating transfer of any target particles captured by the capture device, from the capture device to the detection device.