Separation and concentration of particles

Abstract

Described are devices, methods, and kits for controlled incremental filtration (CIF), as well as methods of designing CIF devices. For example, a method for CIF may modulate a concentration of particles of a desired size in a fluid. The fluid including the particles may be flowed along a flow path through a central channel to contact a plurality of gaps that fluidically couple the central channel to at least one adjacent side channel network. Flow resistance may be decreased along at least a portion of the flow path effective to modulate the concentration of particles. The method may include selecting the plurality of gaps to be larger than the particles. The method may include causing a consistent flow fraction f gap in the central channel to traverse each gap in the plurality of gaps and flow through the at least one side channel network along the flow path.

1 . A controlled incremental filtration (CIF) device, comprising:
 a. a fluid exchange module in a first substrate, the fluid exchange module comprising a corresponding first microfluidic channel and a first array of island structures in the first microfluidic channel, the first array of island structures being arranged in one or more rows that extend along a longitudinal direction of the first microfluidic channel, each island structure in a row being spaced apart from an adjacent island structure in the row to form an opening,   b. wherein the first array of island structures in the fluid exchange module is configured and arranged to shift portions of fluid through the opening between adjacent island structures within a row; and   a particle concentration module, the particle concentration module comprising a corresponding second microfluidic channel and a second array of island structures, each island structure in the second array of island structures being spaced apart from an adjacent island structure in the second array of island structures to form an opening,   c. wherein the second array of island structures in each particle concentration module is configured and arranged to shift portions of fluid through the openings between adjacent island structures in the second array of island structures toward a first side of the second array of island structures, and to focus particles contained within the product fluid along one or more streamlines on a second opposite side of the second array of island structures.   
     
     
         2 . A controlled incremental filtration (CIF) device configured for modulating a concentration of particles of desired size in a fluid in microfluidic flow, comprising:
 a substrate comprising at least one CIF module, the substrate comprising:   a first channel, the first channel extending along a flow path between a first channel flow input and a first channel flow output;   a plurality of micro-features adjacent to the first channel, the plurality of micro-features defining a plurality of gaps, the plurality of micro-features separating the first channel from at least one second channel network, the plurality of gaps configured to fluidically couple the first channel to the at least one second channel network, the at least one second channel network extending along the first channel to at least one second channel output, the at least one second channel network comprising:
 a filtration channel portion comprising: a second channel adjacent to the first channel, at least a portion of the plurality of micro-features, and at least a portion of the plurality of gaps;
 the second channel being characterized by a flow cross-section that increases along the flow path such that the plurality of gaps in the filtration channel portion are characterized by one or more of: a consistent flow fraction f gap  and a plurality of different gap volumetric flow rates; 
 
 the filtration channel portion being characterized by a decreasing flow resistance along at least a portion of the flow path effective to modulate a concentration of particles of a desired size in a fluid in microfluidic flow through said device. 
   
     
     
         3 . The CIF device of  claim 2 , the plurality of gaps in each of the CIF modules being characterized by an average gap cross-sectional area parallel to the flow path, the average gap cross-sectional area being sized compared to the particles of desired size effective to one or more of:
 mitigate or eliminate fouling of the plurality of gaps by the particles; and   mitigate or eliminate steric exclusion of the particles by the plurality of gaps.   
     
     
         4 . The CIF device of  claim 2 , comprising one or more of the following:
 the first channel in each of the CIF modules being fluidically coupled to an input source through the first channel flow input;   the at least one second channel network being fluidically coupled to the input source through the plurality of gaps to the first channel;   the first channel in each of the CIF modules being fluidically coupled to a retentate output reservoir; and   the at least one second channel network in each of the CIF modules being fluidically coupled to a filtrate output reservoir.   
     
     
         5 . The CIF device of  claim 2 , the flow path in each of the CIF modules comprising one or more turns in the substrate. 
     
     
         6 . The CIF device of  claim 2 , the second channel network being characterized by a ratio of a cross-sectional area of the at least one second channel to a cross-sectional area of the first channel, the cross-sectional areas, being perpendicular to the flow path, the ratio increasing along at least a portion of the flow path. 
     
     
         7 . The CIF device of  claim 2 , wherein each of the CIF modules is characterized along the filtration channel portion by a flow cross-sectional area of the first channel perpendicular to the flow path, the flow cross-sectional area of the first channel being constant, increasing, or decreasing along the flow path, or
 each of the CIF modules is characterized along the second filtration channel portion by a flow cross-sectional area of the at least one second channel perpendicular to the flow path, the flow cross-sectional area of the at least one second channel being constant, increasing, or decreasing along the flow path.   
     
     
         8 . The CIF device of  claim 2 , each of the CIF modules being configured, upon conducting the microfluidic flow using a mixture of 1% w/w 4 μm polystyrene microbeads in water at a temperature of 25° C. and a flow pressure of 2 PSI, to concentrate the particles of the desired size in the microfluidic flow from a starting particle concentration at the concentration channel flow input to a final concentration at the first channel flow output by a concentration factor of at least 1.5:1. 
     
     
         9 . The CIF device of  claim 2 , each of the CIF modules being configured to be capable of conducting the microfluidic flow as one or more of: a gravitationally-directed flow, a vacuum directed flow, an electroosmotic directed flow, an electrokinetic directed flow, and a mechanically pumped flow. 
     
     
         10 . The CIF device of  claim 2 , the substrate comprising two or more of the CIF modules, the two or more of the CIF modules being fluidically coupled in series or fluidically coupled in parallel. 
     
     
         11 . The CIF device of  claim 2 , the substrate comprising two or more of the CIF modules, the two or more of the CIF modules being fluidically independent. 
     
     
         12 . The CIF device of  claim 2 , further comprising at least one additional separation device, the at least one separation device fluidically coupled to one or more of: the first channel flow input, the first channel flow output, and the at least one second channel output. 
     
     
         13 . The CIF device of  claim 12 , the at least one additional separation device comprising one or more of: a filter, a centrifuge, an electrophoresis device, a chromatography column, a fluid evaporator, a sedimentation device, a deterministic lateral displacement device, a plasma skimmer, a margination device, a magnetic separator, an ultrasound focusing device, and a density gradient separator. 
     
     
         14 . A controlled incremental filtration (CIF) device configured for modulating a concentration of particles of desired size in a fluid in microfluidic flow, comprising:
 a substrate comprising at least one CIF module, the substrate comprising:   a first channel, the first channel extending along a flow path between a first channel flow input and a first channel flow output;   a plurality of micro-features adjacent to the first channel, the plurality of micro-features defining a plurality of gaps, the plurality of micro-features separating the first channel from at least one second channel network, the plurality of gaps configured to fluidically couple the first channel to the second channel network, the second channel network extending along the first channel to a second channel output, the second channel network comprising:
 a filtration channel portion: a plurality of second channel curves adjacent to the first channel, at least a portion of the plurality of micro-features, and at least a portion of the plurality of gaps;
 the plurality of second channel curves being characterized by a plurality of lengths that decrease along the flow path, each said second channel curve fluidically coupling at least one gap of the plurality of gaps in the filtration channel portion to one or more of: an adjacent gap in the plurality of gaps and an adjacent curve in the plurality of curves; and 
 
 the filtration channel being characterized by a decreasing flow resistance along at least a portion of the flow path effective to modulate a concentration of particles of a desired size in a fluid in microfluidic flow through said device.