Method and system for microfluidic particle orientation and/or sorting

• US 10,393,644 B2
• Filed: 09/07/2017
• Issued: 08/27/2019
• Est. Priority Date: 07/27/2012
• Status: Expired due to Fees

• Current Assignee: Engender Technologies Limited (CRV Holding BV)
• Original Assignee: Engender Technologies Limited (CRV Holding BV)
• Inventors: Simpson, Miriam Cather, Rohde, Charles Alan
• Primary Examiner(s): Matthews, Terrell H
• Application Number:
  US15/697,770
• Publication Number:
  US 20170370822A1
• Time in Patent Office: 719 Days
• Field of Search: 209552
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 15/01 specially adapted for biological cells, e.g. blood cells investigating sedimentation of particle suspensions in blood G01N15/05
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1425 using an analyser being characterised by its control arrangement
• CPC Class Codes: G01N 15/1427 with the synchronisation of components, a time gate for operation of components, or suppression of particle coincidences
• CPC Class Codes: G01N 15/1456 without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/0288 Sorting the particles
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53

Abstract

A system for orienting particles in a microfluidic system includes one or more radiation pressure sources arranged to expose particles to radiation pressure to cause the particles to adopt a particular orientation in the fluid. A system for sorting particles in a microfluidic system includes a detection stage arranged to detect at least one difference or discriminate between particles in the fluid flow past the detection stage, and one or more radiation pressure sources past which the particles move sequentially and a controller arranged to switch radiation energy to cause a change in direction of movement of selected particles in the fluid flow to sort the particles. The particles may be biological particles such as spermatozoa. The radiation pressure may be optical pressure and may be from one or more waveguides which may extend across a channel of the microfluidic system.

Claims

1. A microfluidic system for sexing sperm comprising:

at least one channel configured for flowing a fluid flow between at least one input source and at least two outputs;

an orientation stage arranged downstream from the at least one input source, and comprising at least one optical waveguide configured to expose sperm contained in the flow to radiation pressure for causing at least a majority of the sperm to adopt a particular orientation in the flow;

a detection stage arranged downstream from the orientation stage and comprising an optical detector configured to discriminate between X and Y sperm in the flow; and

a switching stage comprising a plurality of optical waveguides arranged and configured to expose sperm in the flow to radiation pressure for causing a change in direction of movement of selected X or selected Y sperm in the flow so as to sort the selected X or selected Y sperm into one of the at least two outputs based on input from the detection stage.

2. The microfluidic system of claim 1, wherein the optical waveguides are connected to a laser or lasers.

3. The microfluidic system of claim 1, wherein the waveguides extend across the channel or abut the channel of the microfluidic system.

4. The microfluidic system of claim 1, further comprising a controller, wherein the controller is arranged to activate the radiation pressure from the optical waveguides.

5. The microfluidic system of claim 4, wherein the radiation pressure deflects sperm from a flow on one side, across a flow boundary or boundaries, and into a flow towards a selected output.

6. The microfluidic system of claim 1, wherein the optical detector is arranged to discriminate sperm by a fluorescence-based detection technique.

7. The microfluidic system of claim 1, further comprising a focusing stage, arranged before the orientation stage, in fluid communication with the at least one input source, the focusing stage comprising an apparatus configured to provide at least one of a hydrodynamic pressure force and a radiation pressure force, to focus the sperm to a particular location within the fluid.

8. The microfluidic system of claim 3, wherein the plurality of optical waveguides abut the channel from above, below or along the side walls of the channel.

9. The microfluidic system of claim 1, further comprising a cooling stage capable of cooling the fluid and the sperm within the fluid.

10. The microfluidic system of claim 1, wherein the at least one channel has a width of about 10 μ

m to about 500 μ

m.

11. The microfluidic system of claim 1, wherein the at least one channel has a depth of about 5 μ

m to about 500 μ

m.

13. The microfluidic system of claim 1, wherein the plurality of optical waveguides for the switching stage are sequentially arranged.

12. A method of sexting sperm in a microfluidic system, comprising,

forcing sperm to adopt a particular orientation in fluid flow within at least one channel of the microfluidic system by contacting the sperm with a radiation force produced by at least one optical waveguide;

following orientation, discriminating between X and Y sperm in the fluid flow; and

causing a change in the direction of movement of selected X or selected Y sperm in the fluid flow to sort the selected X or selected Y sperm into one of at least two output sources,

wherein the change in direction is caused by contacting the selected X or selected Y sperm with a radiation force produced by a plurality of optical waveguides.