Separation and concentration of particles

Patent metadata

Field	Value
Publication number	US-9789235-B2
Application number	US-201514601205-A
Country	US
Kind code	B2
Filing date	Jan 20, 2015
Priority date	Jan 20, 2014
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

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.

First claim

The invention claimed is:

1. 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 defining in each CIF module:
a central channel, the central channel extending along a flow path between a central channel flow input and a central channel flow output;
a plurality of micro-features adjacent to the central channel, the plurality of micro-features defining a plurality of gaps, the plurality of micro-features separating the central channel from at least one side channel network, the plurality of gaps configured to fluidically couple the central channel to the at least one side channel network, the at least one side channel network extending along the central channel to at least one side channel output, the at least one side channel network comprising one or more of:
a first side channel network portion comprising: a plurality of side channel curves adjacent to the central channel, at least a portion of the plurality of micro-features, and at least a portion of the plurality of gaps;
the plurality of side channel curves being characterized by a plurality of lengths that decrease along the flow path, each side channel curve fluidically coupling at least one gap of the plurality of gaps in the first side channel network portion to one or more of: an adjacent gap in the plurality of gaps and an adjacent curve in the plurality of curves; and

a second side channel network portion comprising: a side channel adjacent to the central channel, at least a portion of the plurality of micro-features, and at least a portion of the plurality of gaps;
the side channel being characterized by a flow cross-section that increases along the flow path such that the plurality of gaps in the second side channel network portion are characterized by one or more of: a consistent flow fraction f gap and a plurality of different gap volumetric flow rates;

the at least one side channel network 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.

2. The CIF device of claim 1 , comprising two of the side channel networks, the two side channel networks being adjacent to the central channel and the two side channel networks being separated by the central channel.

3. The CIF device of claim 1 , the plurality of gaps in each of the CIF module 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 1 , comprising one or more of the following:
the central channel in each of the CIF modules being fluidically coupled to an input source through the central channel flow input;
the at least one side channel network being fluidically coupled to the input source through the plurality of gaps to the central channel;
the central channel in each of the CIF modules being fluidically coupled to a retentate output reservoir; and
the at least one side channel network in each of the CIF modules being fluidically coupled to a filtrate output reservoir.

5. The CIF device of claim 1 , the flow path in each of the CIF modules comprising one or more turns in the substrate.

6. The CIF device of claim 1 , the second side channel network portion being characterized by a ratio of a cross-sectional area of the at least one side channel to a cross-sectional area of the central 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 1 , wherein each of the CIF modules is characterized along the second side channel network portion by a flow cross-sectional area of the central channel perpendicular to the flow path, the flow cross-sectional area of the central channel being constant, increasing, or decreasing along the flow path, or
each of the CIF modules is characterized along the second side channel network portion by a flow cross-sectional area of the at least one side channel perpendicular to the flow path, the flow cross-sectional area of the at least one side channel being constant, increasing, or decreasing along the flow path.

8. The CIF device of claim 1 , 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 central channel flow input to a final concentration at the central channel flow output by a concentration factor of at least 1.5:1.

9. The CIF device of claim 1 , 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 1 , 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 1 , 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 1 , further comprising at least one additional separation device, the at least one separation device fluidically coupled to one or more of: the central channel flow input, the central channel flow output, and the at least one side 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 method for making the CIF device of claim 1 , comprising:
i) preparing an initial design for the CIF device;
ii) selecting a desired flow fraction f gap for the CIF device;
iii) determining a plurality of adjusted dimensions along the flow path;
iv) adapting said initial design to incorporate the plurality of the adjusted dimensions effective to provide a decreasing flow resistance along at least a portion of the flow path effective to modulate the concentration of particles of the desired size in the fluid, thereby providing a complete design for the CIF device; and
v) fabricating the CIF device according to said complete design.

15. The method of claim 14 , the adjusted dimensions along the flow path comprising one or more of:
in a first side network portion, a decreasing length of each of a plurality of side channel curves, the plurality of side channel curves being adjacent to the central channel in the first side channel network portion; and
in a second side network portion, an increasing ratio of a cross-sectional area of at least one side channel to a cross-sectional area of the central channel, the at least one side channel being adjacent to the central channel in the second side networ

Assignees

• Halcyon Biomedical Incorporated
• The Administrators Of The Tulane Educational Fund

Inventors

• Gifford Sean C
• Shevkoplyas Sergey S

Classifications

• A61M1/3695 Primary

  with sedimentation by gravity · CPC title

• B01D61/14

  Ultrafiltration; Microfiltration · CPC title

• B01D21/006

  with co-current flow direction of liquid and solid particles · CPC title

• A61M1/0272 Primary

  Apparatus for treatment of blood or blood constituents prior to or for conservation, e.g. freezing, drying or centrifuging · CPC title

• B01L3/502753

  characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation · CPC title