Microfluidic method and system for isolating particles from biological fluid

• US 8,790,916 B2
• Filed: 05/13/2010
• Issued: 07/29/2014
• Est. Priority Date: 05/14/2009
• Status: Expired due to Fees

• Current Assignee: Genestream, Inc.
• Original Assignee: Genestream, Inc.
• Inventors: Achrol, Achal Singh, Sethu, Palaniappan
• Primary Examiner(s): Chin, Chris L
• Assistant Examiner(s): MOERSCHELL, RICHARD P
• Application Number:
  US12/779,746
• Publication Number:
  US 20110020459A1
• Time in Patent Office: 1,538 Days
• Field of Search: None
• US Class Current: 435/287.1
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/043 magnetic forces
• 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: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• 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 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 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• 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

Abstract

The invention relates to a system and method for isolating particles from a biological fluid, including: obtaining a sample of biological fluid from a source (e.g. a patient) in which the sample contains particles of multiple sample particle types; tagging particles in the sample with tagging agents, including mixing the sample with a solution of magnetic tagging agents that selectively bind to particles of at least one of the sample particle types, thereby forming a group of tagged particles in the sample; passing the sample through a magnetic conduit having a magnetic field that interacts with at least some of the tagged particles; sorting the particles of the sample into multiple groups based on the interaction between the tagged particles and the magnetic field; and optionally returning selected portions of the processed fluid back to its source with or without the addition of appropriate therapeutic agents.

Claims

1. A microfluidic system for isolating particles from biological fluid of a patient, comprising:

a sampling module including a cannula coupled to the patient that obtains a sample of biological fluid from the patient, wherein the sample contains particles of multiple sample particle types;

a microfluidic tagging conduit, fluidly coupled to the sampling module at a point-of-care of the patient, having;

a first inlet that receives the sample;

a second inlet that receives a solution comprising a magnetic tagging agent, wherein the magnetic tagging agent selectively binds to and tags particles of at least one particle type of the multiple sample particle types; and

a textured surface that induces turbulent mixing of the particles with the magnetic tagging agent, thus producing a set of tagged particles; and

a microfluidic magnetic conduit, fluidly coupled to the microfluidic tagging conduit and having at least one magnet providing a magnetic field that interacts with the set of tagged particles, such that the particles in the sample are sorted into at least two groups based on an interaction between the set of tagged particles and the magnetic field, wherein the microfluidic magnetic conduit includes a serpentine-shaped sorting region including a first surface configured to immobilize a first portion of the set of tagged sample particles by the magnetic field and allow passage of a set of untagged sample particles, and a second surface configured to immobilize a second portion of the set of tagged sample particles by the magnetic field and allow passage of the set of untagged sample particles, wherein the first surface and the second surface are coupled by a channel not within the magnetic field, that angularly displaces flow passing the first surface toward the second surface.

2. The system of claim 1, wherein the textured surface of the tagging conduit includes herringbone structures.

3. The system of claim 1, wherein the magnetic conduit includes a first outlet through which untagged particles flow to form a first group, and a surface, onto which the magnetic field captures at least a portion of the tagged particles to form a second group.

4. The system of claim 3, wherein the magnetic conduit includes a second surface onto which the magnetic field captures a second portion of the tagged particles to form a third group.

5. The system of claim 4, wherein the second surface is downstream of the first surface in the magnetic conduit.

6. The system of claim 1, wherein the microfluidic magnetic conduit includes a first outlet through which the set of untagged particles flow to form a first group, and a second outlet through which the the set of tagged particles is diverted to form a second group.

7. The system of claim 6, wherein the second outlet is downstream of the first outlet.

8. A microfluidic system for isolating particles from a sample of biological fluid of a patient comprising sample particles of interest, the microfluidic system comprising:

a sampling module comprising a tubing that is configured to couple, at a point-of-care of the patient, to a cannula that obtains the sample of biological fluid from the patient;

a microfluidic tagging conduit, comprising;

a first inlet region configured to fluidically couple to the tubing of the sampling module to receive the sample,

a second inlet region configured to receive a solution of a magnetic tagging agent that selectively binds to and tags sample particles of interest, and configured to merge the magnetic tagging agent into the sample,

a serpentine-shaped mixing region comprising a textured surface configured to induce turbulent mixing of the sample and the magnetic tagging agent, creating an unsorted mixture comprising a set of tagged sample particles and a set of untagged sample particles;

a microfluidic magnetic conduit configured to fluidically couple to the serpentine-shaped mixing region, the microfluidic magnetic conduit comprising a magnetic conduit inlet configured to receive the unsorted mixture, a first magnetic conduit outlet, and a second magnetic conduit outlet; and

a magnet providing a magnetic field at the microfluidic magnetic conduit, wherein the magnetic field is configured to;

allow the set of untagged sample particles to flow through the first magnetic conduit outlet, thereby forming a first group of sample particles and

allow flow of the set of tagged sample particles through the second magnetic conduit outlet based on an interaction between the magnetic field and the set of tagged sample particles, thereby forming a second group of sample particles; and

wherein the microfluidic magnetic conduit includes a serpentine-shaped sorting region including a first surface configured to immobilize a first portion of the set of tagged sample particles by the magnetic field and allow passage of a set of untagged sample particles, and a second surface configured to immobilize a second portion of the set of tagged sample particles by the magnetic field and allow passage of the set of untagged sample particles, wherein the first surface and the second surface are coupled by a channel not within the magnetic field, that angularly displaces flow passing the first surface toward the second surface.

9. The system of claim 8, wherein the tubing of the sampling module is configured to couple to a catheter inserted in the patient at the point-of-care.

10. The system of claim 8 further comprising a perturbing mechanism configured to be coupled to the sampling module.

11. The system of claim 10, wherein the perturbing mechanism comprises a rocker.

12. The system of claim 8, wherein a portion of the second inlet region is configured to divide and flank a portion of the first inlet region.

13. The system of claim 8, wherein the microfluidic magnetic conduit is further configured to couple to a buffer inlet for introducing a buffer stream, wherein the magnetic field is configured to divert flow of the set of tagged sample particles into the buffer solution and through the second magnetic conduit outlet, in a continuous flow separation.

14. The system of claim 8, wherein the microfluidic magnetic conduit further comprises a third magnetic conduit outlet.

15. The system of claim 14, wherein the magnetic field is configured to divert flow of a second set of tagged sample particles through the third magnetic conduit outlet, thereby forming a third group of sample particles.

16. The system of claim 14, wherein the microfluidic magnetic conduit comprises a first branch terminating in the first magnetic conduit outlet, a second branch terminating in the second magnetic conduit outlet, and a third branch terminating in the third magnetic conduit outlet.

17. The system of claim 16, wherein the first, second, and third branches are located at substantially the same longitudinal point along the length of the microfluidic magnetic conduit.

18. The system of claim 8, wherein the magnet is an electromagnet.

19. The system of claim 8, wherein the microfluidic magnetic conduit is further configured to be fluidically coupled to a second magnetic tagging solution inlet, downstream of the second surface, and configured to receive a second solution of magnetic tagging agents that selectively bind to and tag other sample particles of interest.

20. The system of claim 8, further comprising detection apparatus configured to enumerate particles in at least one of the first group of sample particles and the second group of sample particles.

21. The system of claim 20, wherein the detection apparatus measures an electrical parameter that is altered by the presence of at least one particle of the first group of sample particles and the second group of sample particles.