Liquid to liquid biological particle fractionation and concentration

Abstract

The present disclosure provides for devices, systems and methods for fractionation and concentration of particles from a fluid sample. This includes a cartridge containing staged filters having porous surface in series of decreasing pore size for capture of particles from a fluid sample; and a permeate pressure source in fluid communication with the cartridge; wherein the particles are eluted from the porous surfaces and dispensed in a reduced fluid volume.

What is claimed is: 
     
         1 . A device for fractionation and concentration of particles from a fluid sample, the device comprising:
 a cartridge containing staged filters having porous surface in series of decreasing pore size for capture of particles from a fluid sample; and   a permeate pressure source in fluid communication with the cartridge;   wherein the particles are eluted from the porous surfaces and dispensed in a reduced fluid volume.   
     
     
         2 . The device in  claim 1 , further comprising a connecting portion for connection to a concentrating unit. 
     
     
         3 . The device in  claim 1 , wherein the filters are separated by a small interstitial space. 
     
     
         4 . The device in  claim 1 , wherein the membrane filters are separated by a filter support with flow channel connecting the permeate of one filter with the retentate of an adjacent smaller pore filter. 
     
     
         5 . The device in  claim 1 , wherein a sample is introduced into the device perpendicular to a surface of each filter. 
     
     
         6 . The device in  claim 1 , wherein valved fluidic connections connect the interstitial space or flow channels between filters. 
     
     
         7 . The device in  claim 1 , wherein pneumatic, hydraulic, or mechanical valves are integrated into the cartridge device. 
     
     
         8 . The device in  claim 1 , wherein the filters are one or more of a flat membrane filter, a flat ceramic filter, an affinity-based filter, a flat depth filter, an electrostatically charged filter, or a microsieve. 
     
     
         9 . The device in  claim 1 , further comprising an elution buffer distribution manifold including flow control orifice. 
     
     
         10 . The device in  claim 1 , wherein elution is performed tangential to a surface of each filter. 
     
     
         11 . A system for fractionation and concentration of particles from a fluid sample, the system comprising:
 a reservoir holding a fluid sample;   a fractionation and concentration cartridge including two or more staged filters;   a permeate pressure device in fluid communication with the cartridge;   a concentrating unit including an actuating integral valving to move sample through the cartridge; and   a fluid dispenser source for collecting concentrated samples from the cartridge staged filters;   wherein the fluid sample is moved through the concentrating unit, then the concentrated samples are eluted from the filters and dispensed.   
     
     
         12 . The system in  claim 11 , wherein a flow sensor is in fluid communication with the sample flow into the cartridge. 
     
     
         13 . The system in  claim 11 , wherein a flow sensor is in fluid communication with the permeate flow out of the cartridge. 
     
     
         14 . A method for rapid fractionation and concentration of particles from a fluid sample, the method comprising:
 introducing a sample into the sample reservoir;   initiating a fractionation and concentration cycle;   passing the fluid sample through a series of filters;   eluting a plurality of particles of decreasing particle size from each filter stage; and   extracting a concentrated sample from each filter stage.   
     
     
         15 . The method in  claim 14 , wherein the eluting further comprises tangential flushing of a porous surface within the cartridge with an elution fluid. 
     
     
         16 . The method in  claim 15 , wherein the elution fluid is one or more of a liquid elution fluid and a wet foam. 
     
     
         17 . The method in  claim 14 , wherein blinding of the filter is prevented using one or more of high-frequency backpulsing and oscillating tangential flow.