Operatorless particle processing systems and methods

Patent metadata

Field	Value
Publication number	US-9964968-B2
Application number	US-201414210381-A
Country	US
Kind code	B2
Filing date	Mar 13, 2014
Priority date	Mar 14, 2013
Publication date	May 8, 2018
Grant date	May 8, 2018

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.

First claim

What is claimed is:

1. A method for automatically operating a particle processing system in an operatorless fashion during a particle processing operation, the method comprising:
providing a stream of particles from a particle delivery assembly to a particle processing assembly, the particle processing assembly including a particle detection region and a particle processing region;
driving the stream at an input oscillation frequency, amplitude, and phase to form droplets;
generating a first image of the stream during the particle processing operation;
determining, during the particle processing operation, a first value for a physical dimension of the stream from the first image;
determining, during the particle processing operation, a first value of an operational characteristic of the stream based on the first determined value of the physical dimension of the stream, wherein the operational characteristic is selected from one of a drop delay time and a droplet break-off point;
determining if the operational characteristic meets a predetermined criteria; and
automatically adjusting, during the particle processing operation, an operational parameter associated with the particle delivery assembly, wherein the operational parameter is selected from at least one of the input oscillation frequency, amplitude, and phase, in response to determining that the operational characteristic does not meet the predetermined criteria.

2. The method of claim 1 , further comprising:
directing a radiation source from a signal source assembly into the particle processing assembly to interrogate the particles;
receiving a signal at a signal detector assembly from the particle processing assembly; and
collecting the particles from the particle processing assembly in a particle collection assembly.

3. The method of claim 1 , further comprising:
generating a second image of the droplet stream;
determining a second value for the physical dimension of the stream from the second image;
determining, during the particle processing operation, a second value of the operational characteristic of the stream based on the second determined value of the physical dimension of the stream;
determining, during the particle processing operation, a difference between the first value of the operational characteristic and the second value of the operational characteristic; and
setting the predetermined criteria equal to this difference.

4. The method of claim 1 , wherein the particle processing assembly is provided as a microfluidic assembly having at least one microfluidic channel.

5. The method of claim 1 , wherein the step of automatically adjusting includes a remote processor remotely controlling one or more of the operational parameters of the particle delivery assembly.

6. The method of claim 1 , wherein the at least one operational characteristic includes a drop delay, the method further comprising automatically determining the drop delay during the particle processing operation by:
driving the stream of particles at an input oscillation frequency and amplitude to form droplets;
generating at least one image of the droplet stream between the particle detection region and a droplet break-off point;
determining an undulation length of the stream;
calculating a drop delay time for the stream to travel from the particle detection region to the droplet break-off point based on the undulation length of the stream and a distance between the particle detection region and the break-off point; and
providing the calculated drop delay time to a controller of a charging device.

7. The method of claim 6 , further comprising:
determining the distance between the detection region and the break-off point based on a determination of the location of the break-off point during the particle processing operation.

8. The method of claim 6 , further comprising:
comparing the automatically determined drop delay to one of a previously automatically determined drop delay and a predetermined drop delay value; and
providing an input to a controller of a droplet generator to control the input oscillation frequency, amplitude or phase based on the automatically determined drop delay.

9. The method of claim 1 , wherein the at least one operational characteristic includes a droplet break-off point and wherein the first image of the stream encompasses the droplet break-off point, the method further comprising automatically determining the longitudinal position of the droplet break-off point by:
determining a first longitudinal zero-width stream location based on the first image signal where the width of the stream first goes to zero;
generating a second image of the stream that encompasses the droplet break-off point;
determining a second longitudinal zero-width stream location based on the second image signal where the width of the stream first goes to zero;
determining a difference between the first and second longitudinal zero-width stream locations; and
automatically adjusting the input oscillation phase if the difference between the first and second longitudinal zero-width stream locations exceeds a predetermined threshold criteria.

10. The method of claim 9 , further comprising:
determining, based on the first image, where the width of the stream first achieves a local minimum above the first longitudinal zero-width stream location and determining a first local-minimum stream width at that local minimum location;
determining, based on the second image, where the width of the stream first achieves a local minimum above the second longitudinal zero-width stream location and determining a second local-minimum stream width at that local minimum location;
determining a difference between the first and second local-minimum stream widths; and
automatically adjusting the input oscillation amplitude if the difference between the first and second local-minimum stream widths exceeds a predetermined threshold criteria.

11. The method of claim 9 , further comprising:
synchronizing the generation of the first and second images with the input oscillation frequency.

Assignees

• Cytonome St Llc

Inventors

• Sharpe Johnathan Charles
• Sedoglavich Nemanya
• Shapiro Vladimir
• Ehrlich Stuart R
• Perrault Jr Donald Francis
• Morad Blair D

Classifications

• G01N15/1404

  Handling flow, e.g. hydrodynamic focusing · CPC title

• G01N2015/1452

  Adjustment of focus; Alignment · CPC title

• G05D21/02 Primary

  characterised by the use of electric means · CPC title

• G01N2015/1406

  Control of droplet point · CPC title

• G01N2015/1006

  for cytology · CPC title