Systems and methods for the capture and separation of microparticles

Abstract

Systems and methods are provided for capturing and/or isolating target microparticles. In one aspect, a method for capturing target microparticles is disclosed. The method includes: forming a fluid including the target microparticles, non-target microparticles, and magnetic beads, the magnetic beads having a stronger affinity with the target microparticles than with the non-target microparticles; flowing the fluid through a multidirectional microchannel; and applying a magnetic field to the fluid while the fluid is flowing through at least a portion of the microchannel to effect capture of at least a portion of the target microparticles onto the magnetic beads. Such a method can further includes passing the fluid having exited from the microchannel through a separator while subjecting the fluid to a second magnetic field so as to isolate the target microparticles. In addition, devices and systems are disclosed for capturing and/or isolating target microparticles based on magnetic manipulation.

What is claimed is: 
     
         1 . A method for capturing target microparticles, comprising:
 forming a fluid including the target microparticles, non-target microparticles, and magnetic beads, the magnetic beads having a stronger affinity with the target microparticles than with the non-target microparticles;   flowing the fluid through a multidirectional microchannel; and   applying a magnetic field to the fluid while the fluid is flowing through at least a portion of the microchannel to effect capture of at least a portion of the target microparticles onto the magnetic beads.   
     
     
         2 . The method of  claim 1 , wherein the flowing further comprises flowing the fluid though a substantially planer microchannel. 
     
     
         3 . The method of  claim 1 , wherein the flowing further comprises flowing the fluid through a microchannel having a width between 100 μm and 200 μm. 
     
     
         4 . The method of  claim 1 , wherein the flowing further comprises flowing the fluid through a serpentine shaped microchannel having a plurality of straight segments. 
     
     
         5 . The method of  claim 4 , further comprising positioning the microchannel such that each of the plurality of straight segments is substantially perpendicular to the magnetic field. 
     
     
         6 . The method of  claim 1 , wherein applying the magnetic field further comprises placing a permanent magnet near the microchannel. 
     
     
         7 . The method of  claim 6 , wherein the flowing further comprises flowing the fluid through a microchannel having a width which increases as the multidirectional microchannel extends away from the permanent magnet. 
     
     
         8 . The method of  claim 1 , wherein the target particles are selected from the group consisting of bacteria, viruses, micelles, polypeptides, nucleic acids, biological cells, and particles coated with a ligand, polypeptide or nucleic acid. 
     
     
         9 . The method of  claim 1 , wherein the target particles comprise cancerous leukocytes. 
     
     
         10 . The method of  claim 1 , wherein the magnetic beads comprise a functional group selected from the group consisting of a nucleic acid aptamer, a peptide, a small molecule ligand, and an antibody. 
     
     
         11 . The method of  claim 1 , wherein the magnetic beads comprise at least one antibody. 
     
     
         12 . The method of  claim 1 , wherein the target microparticles comprise microparticles having an average size of 5 μm to 20 μm. 
     
     
         13 . A method for isolating target microparticles, comprising:
 forming a fluid including the target microparticles, non-target microparticles, and magnetic beads, the magnetic beads having a stronger affinity with the target microparticles than with the non-target microparticles,   flowing the fluid through a multidirectional microchannel;   applying a first magnetic field to the fluid while the fluid is flowing through at least a portion of the microchannel to effect capture of at least a portion of the target microparticles onto the magnetic beads; and   passing the fluid having exited from the microchannel through a separator while subjecting the fluid to a second magnetic field so as to isolate the target microparticles.   
     
     
         14 . The method of  claim 13 , wherein the flowing further comprises flowing the fluid through a serpentine shaped microchannel having a plurality of straight segments. 
     
     
         15 . The method of  claim 13 , wherein the first magnetic field and the second magnetic field are produced by a same magnet. 
     
     
         16 . A device for capturing target microparticles from a fluid comprising the target microparticles, non-target microparticles, and magnetic beads having a stronger affinity with the target microparticles than with the non-target microparticles, comprising:
 a multidirectional microchannel adapted to permit the fluid to flow through, and   one or more magnets positioned such that a magnetic field is applied to the fluid while the fluid is flowing through at least a portion of the microchannel, to thereby effect capture of at least a portion of the target microparticles onto the magnetic beads.   
     
     
         17 . The device of  claim 16 , further comprising:
 a first inlet, coupled to the microchannel, for introducing the target microparticles and non-target microparticles into the microchannel, and   a second inlet, coupled to the microchannel, for introducing a suspension including the magnetic beads into the microchannel.   
     
     
         18 . The device of  claim 16 , further comprising a separator portion, fluidically coupled with the microchannel and configured to isolate the target microparticles from the fluid. 
     
     
         19 . The device of  claim 18 , wherein the separator portion further comprises a buffer inlet for introducing a buffer to the fluid so as to isolate the target particles. 
     
     
         20 . The device of  claim 18 , further comprising a target microparticle collection outlet, coupled to the separator portion, for collecting magnetic beads-bound target microparticles. 
     
     
         21 . The device of  claim 18 , wherein the separator portion is formed on the same substrate as the microchannel.