OPERATORLESS PARTICLE PROCESSING SYSTEMS AND METHODS

• US 20180356846A1
• Filed: 05/07/2018
• Published: 12/13/2018
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Inventors: Sharpe, Johnathan Charles, Sedoglavich, Nemanya, Shapiro, Vladimir, Ehrlich, Stuart R., Perrault, JR., Donald Francis, Morad, Blair D.
• Granted Patent: US 10,871,790 B2
• Time in Patent Office: Days
• 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 15/1484 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 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1406 Control of droplet point
• CPC Class Codes: G01N 2015/1452 Adjustment of focus; Alignment
• CPC Class Codes: G05D 21/02 characterised by the use of electric means

Abstract

The present disclosure provides improved particle processing (e.g., cytometry and/or cell purification) systems and methods that can operate in an autonomous fashion. More particularly, the present disclosure provides for assemblies, systems and methods for analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting and/or enriching) particles (e.g., cells, microscopic particles, etc.) where human intervention is not required and/or is minimized. The systems, assemblies and methods of the present disclosure advantageously improve run performance of particle processing systems (e.g., cell purification systems, cytometers) by significantly reducing and/or substantially eliminating the burden of operation for human intervention by automating numerous functions, features and/or steps of the disclosed systems and methods.

Claims

1. A method for automatically aligning a microfluidic chip for a particle processing system, the method comprising:

receiving a microfluidic chip into a chip receptacle;

illuminating the microfluidic chip with a radiation source;

detecting extinction signals;

coarsely scanning the chip in a first-direction, a second-direction, or both the first and second-direction to generate extinction signals;

determining a coarse slant angle based on a dimension determined from the coarse scanning and a known dimension of the microfluidic chip;

rotating the microfluidic chip by the negative of the coarse slant angle;

finely scanning the chip in a first-direction, a second-direction, or both the first- and second-direction to generate extinction signals;

determining a fine slant angle based on a dimension determined from the fine scanning and a known dimension of the microfluidic chip; and

rotating the microfluidic chip by the negative of the fine slant angle.

2. The method of claim 1, wherein the microfluidic chip is removably received into the chip receptacle.

3. The method of claim 1, wherein the microfluidic chip includes a pair of relatively widely separated fiducials and the step of coarsely scanning includes scanning at least one of the fiducials.

4. The method of claim 1, wherein a coarse scanning step increment ranges from approximately 50 microns to 200 microns.

5. The method of claim 1, wherein a fine scanning step increment ranges from approximately 5 microns to 50 microns.

6. The method of claim 1, wherein the step of coarsely scanning includes moving the microfluidic chip relative to a radiation source.

7. The method of claim 1, wherein the step of coarsely scanning includes scanning the microfluidic chip across a plurality of microfluidic channels.

8. The method of claim 1, wherein the microfluidic chip includes a plurality of pinholes associated one or more microfluidic channels and the step of coarsely scanning includes scanning the pinholes associated with the one or more microfluidic channels.

9. The method of claim 1, further comprising:

determining a first-direction coarse misalignment distance based on the coarse scanning; and

translating the microfluidic chip by the negative of the first-direction coarse misalignment position.

10. The method of claim 9, further comprising:

determining a first-direction fine misalignment distance based on the fine scanning; and

translating the microfluidic chip by the negative of the first-direction fine misalignment position.

11. A method for automatically aligning a particle processing system, the method comprising:

flowing a fluid stream through the particle processing system;

illuminating the fluid stream with the radiation source;

detecting at least one of an extinction signal, a scatter signal, and a fluorescence signal;

in a first alignment step, aligning the center of the fluid stream with the radiation source and at least one of the extinction, scatter, and fluorescence detector assemblies by automatically moving the fluid stream to maximize at least one of the extinction signal, scatter signal, and fluorescence signal; and

in a second alignment step, aligning the extinction, scatter, and fluorescence detector assemblies with a particle being interrogated by the radiation source, by automatically moving one or more signal collection optical components and/or the extinction, scatter, and fluorescence detector assemblies to collectively optimize the signals received by all of the detector assemblies.

12. The method of claim 11, further comprising:

nominally aligning a radiation source with an extinction detector assembly, a scatter detector assembly, and a fluorescence detector assembly when the radiation source and detector assemblies are mounted to the particle processing system.

13. The method of claim 11, wherein automatically moving the fluid stream consists of translating the fluid stream in three directions.

14. A method for automatically aligning a particle processing system, the method comprising:

comparing one or more operational parameters to one or more first alignment procedure threshold criteria;

automatically running a first alignment procedure if the first alignment procedure threshold criteria are met;

comparing one or more operational parameters to one or more second alignment procedure threshold criteria; and

automatically running a second alignment procedure if the second alignment procedure threshold criteria are met.