Sheath flow devices and methods

Abstract

The invention relates generally to fluid processing and, in particular aspects, processing fluids for detection, selection, trapping and/or sorting of particulate moieties. Sheath flow devices described allow isolation of target species from fluid samples while avoiding non-specific binding of unwanted species to the surfaces of the separation device. Biological fluid processing, detection, sorting or selection of cells, proteins, and nucleic acids is described. The invention finds particular use in diagnostic settings, analyzing a patient's medical condition, monitoring and/or adjusting a therapeutic regimen and producing cell based products.

1 . A method of separating a target species from a fluid sample in a sheath flow device, comprising:
 (a) establishing a laminar sheath of buffer flow along a planar surface of the sheath flow device;   (b) establishing a laminar flow of the fluid sample adjacent to the laminar sheath of buffer flow; and   (c) deflecting the target species from the laminar flow of the fluid sample and into the laminar sheath of buffer flow;   wherein the laminar sheath of buffer flow and the laminar flow of the fluid sample are adjacent.   
     
     
         2 . The method of  claim 1 , further comprising establishing a second laminar sheath of buffer flow, adjacent to the laminar flow of the fluid sample, wherein (b) comprises establishing the laminar flow of the fluid sample between the first and second laminar buffer flows. 
     
     
         3 . The method of  claim 2 , wherein establishing the first and second laminar sheaths of buffer flow and the laminar flow of the fluid sample are sufficient to maintain separate flow planes substantially free of turbulent flow. 
     
     
         4 . The method of  claim 3 , wherein deflecting the target species from the laminar flow of the fluid sample and into the laminar sheath of buffer flow comprises using at least one of a magnetic force, an acoustic force, an electrophoretic force and an optical force. 
     
     
         5 . The method of  claim 4 , wherein the target species comprises at least one of a cell, a bacterium, a virus, a protein and a nucleic acid. 
     
     
         6 . The method of  claim 5 , wherein the targets species is isolated in a trapping station over which the laminar sheath of buffer flow passes. 
     
     
         7 . The method of  claim 6 , wherein the trapping station employs magnetic force in order to trap the targets species selectively labeled with magnetic particles. 
     
     
         8 . The method of  claim 7 , wherein the target species is a circulating tumor cell and the fluid sample is whole blood. 
     
     
         9 . A method of analyzing a patient the method comprising:
 (a) receiving a sample comprising tumor cells from a patient;   (b) separating said tumor cells from the sample by a separation method comprising:
 (i) labeling the sample with magnetic particles having a specific affinity for said tumor cells, thereby producing a labeled sample, 
 (ii) passing the labeled sample through a fluidic device comprising a sorting region having a magnetic field gradient effective to deflect and/or trap the magnetic particles from the labeled sample and thereby separate the tumor cells from the sample, wherein the sample flows in a sheath of buffer solution to reduce nonspecific binding of the sample to the fluidic device; and 
   (c) characterizing the tumor cells separated from the sample in (b).   
     
     
         10 . The method of  claim 9 , wherein the characterizing in (c) provides information for diagnosing a condition, screening for a clinical trial, assessing the effectiveness of a therapeutic treatment, and measuring the effectiveness of surgery. 
     
     
         11 . The method of  claim 9 , wherein the sample is a fluid sample taken from the patient. 
     
     
         12 . The method of  claim 9 , wherein the sample is not taken from a biopsy of the patient. 
     
     
         13 . The method of  claim 9 , wherein the sample is a blood sample. 
     
     
         14 . The method of  claim 13 , wherein the tumor cells are circulating tumor cells from a non-haematologic cancer. 
     
     
         15 . The method of  claim 9 , wherein the characterizing is a count of said tumor cells. 
     
     
         16 . The method of  claim 9 , wherein the characterizing is a molecular characterization of said tumor cells. 
     
     
         17 . The method of  claim 16 , wherein said molecular characterization is a genetic mutation in said tumor cells. 
     
     
         18 . A method of monitoring and, if appropriate, adjusting a patient's treatment regimen, the method comprising:
 (a) receiving a sample comprising tumor cells from a patient undergoing a first treatment regimen;   (b) separating said tumor cells from the sample by a separation method comprising:
 (i) labeling the sample with magnetic particles having a specific affinity for said tumor cells, thereby producing a labeled sample, 
 (ii) passing the labeled sample through a fluidic device comprising a sorting region having a magnetic field gradient effective to deflect and/or trap the magnetic particles from the labeled sample and thereby separate the tumor cells from the sample, wherein the sample flows in a sheath of buffer solution to reduce nonspecific binding of the sample to the fluidic device; and 
   (c) characterizing the tumor cells separated from the sample in (b) to suggest a future treatment for the patient.   
     
     
         19 . The method of  claim 18 , wherein the first treatment regimen is a chemotherapy regimen. 
     
     
         20 . The method of  claim 19 , wherein the future treatment is a different chemotherapy regimen. 
     
     
         21 . The method of  claim 18 , wherein suggesting the future treatment for the patient comprises predicting a future effectiveness of the first treatment regimen. 
     
     
         22 . The method of  claim 18 , wherein suggesting a future treatment for the patient comprises identifying a second treatment regimen that is different than the first treatment regimen and accounts for a characteristic of the tumor cells not previously observed for the patient. 
     
     
         23 . The method of  claim 22 , further comprising:
 (d) receiving a sample comprising tumor cells from the patient after the patient has undergone the second treatment regimen; and   (e) thereafter performing (b) and (c) on the sample and tumor cells received in (d).   
     
     
         24 . A method of providing cell based products, the method comprising:
 (a) receiving a sample comprising target cells;   (b) separating said target cells from the sample by a separation method comprising:
 (i) labeling the target cells with magnetic particles having a specific affinity for said target cells, thereby producing a population of labeled cells in the sample, 
 (ii) passing the sample through a fluidic device comprising a sorting region having a magnetic field gradient effective to deflect and/or trap at least a portion of the population of labeled cells from the sample and thereby separate the target cells from the sample, wherein the sample flows in a sheath of buffer solution to reduce nonspecific binding of the sample to the fluidic device; and 
   (c) deriving a cell based product from the target cells separated from the sample in (b).   
     
     
         25 . The method of  claim 24 , further comprising treating the target cells separated from the sample in (b) to produce the cell based product. 
     
     
         26 . The method of  claim 25 , wherein the target cells are stem cells and treating the target cells comprising treating the stem cells to become an effective therapeutic agent. 
     
     
         27 . The method of  claim 26 , wherein treating the stem cells to become an effective therapeutic agent comprises differentiating the stem cells to produce a more specific cell type. 
     
     
         28 . The method of  claim 24 , wherein the sample is a fluid sample taken from a patient. 
     
     
         29 . The method of  claim 28 , wherein the fluid sample is a blood sample. 
     
     
         30 . The method of  claim 24 , further comprising characterizing the target cells separated from the sample in (b). 
     
     
         31 . The method of  claim 30 , wherein the characterizing is a count of said target cells. 
     
     
         32 . The method of  claim 30 , wherein the characterizing is a molecular characterization of said target cells. 
     
     
         33 . The method of  claim 32 , wherein said molecular characterization is a genetic sequence of said target cells. 
     
     
         34 . The method of any of  claims 9 ,  18 , and  24 , wherein the sorting region has a substantially rectangular interior space for bounding the sample flow and the sheath of buffer solution, wherein the interior space has first and second lateral dimensions transverse to the sample flow, wherein the second lateral dimension is at least about 2 times larger than the first lateral dimension such that nonspecific binding is reduced along the larger of the first and second lateral dimensions.