US-12623254-B2 - Systems and methods for particle sorting with automated adjustment of operational parameters

US12623254B2US 12623254 B2US12623254 B2US 12623254B2US-12623254-B2

Abstract

Systems and methods for particle sorting are presented including a monitoring system downstream of a particle separator or sorter. The system can utilize the monitoring system to adjust or calibrate operational parameters of the system in real time. When a particle of interest is mis-sorted, the probability is high that the particle of interest has been sorted into a non-targeted sortable unit that was adjacent in sequence to the sortable unit that was expected to include the particle of interest. The monitoring system monitors non-targeted sortable units in the system that were adjacent in sequence to targeted sortable units that are predicted to contain particles of interest. Signals from the monitoring system enable automated adjustment or calibration of operational parameters of the system such as sort delay or purity mask parameters.

Inventors

Gary Durack
William J. Williams, V

Assignees

CYTONOME/ST, LLC

Dates

Publication Date: 20260512
Application Date: 20231020

Claims (20)

1 . A system for sorting particles flowing in a fluid stream, comprising: a particle delivery device for delivering a sequence of two or more sortable units from a fluid stream to an inspection zone; an electromagnetic radiation source for interrogating the two or more sortable units at the inspection zone; a sorter downstream of the electromagnetic radiation source to sort the two or more sortable units based on a characteristic thereof using a sort logic; a monitoring system downstream of the sorter associated with a single output pathway of the system to interrogate non-targeted sortable units that were adjacent to targeted sortable units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units, the single output pathway associated with a flow of the adjacent non-targeted sortable units; and one or more processing units operatively connected to the sorter and the monitoring system, the processing units configured to execute instructions to adjust an operational parameter of the sort logic by: causing the sorter to direct the adjacent non-targeted sortable units to the single output pathway, and to direct the targeted sortable units away from the single output pathway; interrogating, by the monitoring system, the adjacent non-targeted sortable units; and adjusting the operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units by the monitoring system.
2 . The system of claim 1 , wherein at least one adjacent non-targeted sortable unit was upstream in sequence from at least one targeted sortable unit that included one or more particles having the predetermined characteristic of interest in the fluid stream.
3 . The system of claim 1 , wherein at least one adjacent non-targeted sortable unit was downstream in sequence from at least one targeted sortable unit that included one or more particles having the predetermined characteristic of interest in the fluid stream.
4 . The system of claim 1 , wherein the sorter deflects the targeted sortable units that are predicted to include one or more particles having the predetermined characteristic of interest from the fluid stream.
5 . The system of claim 1 , wherein the sorter deflects the adjacent non-targeted sortable units from the fluid stream.
6 . The system of claim 1 , wherein: the single output pathway is a first pathway; to direct the targeted sortable units away from the single output pathway comprises directing the targeted sortable units to a second pathway, separate from the first pathway; and the one or more processing units are further configured to cause the sorter to direct non-adjacent non-targeted sortable units to a third pathway, separate from the first and second pathways.
7 . The system of claim 1 , wherein the targeted sortable units that are predicted to include one or more particles having the predetermined characteristic of interest or the adjacent non-targeted sortable units are fluid droplets.
8 . The system of claim 1 , wherein the targeted sortable units that are predicted to include one or more particles having the predetermined characteristic of interest or the adjacent non-targeted sortable units are sortable fluid segments of the fluid stream flowing in a microfluidic channel.
9 . The system of claim 1 , wherein the monitoring system interrogates the adjacent non-targeted sortable units using the electromagnetic radiation source.
10 . The system of claim 1 , wherein the processing unit is configured to execute instructions to sweep the sort delay parameter to determine crossing sort delay values where an intensity value received from the monitoring system crosses a threshold intensity value.
11 . The system of claim 1 , wherein the monitoring system includes a second electromagnetic radiation source to interrogate the adjacent non-targeted sortable units.
12 . The system of claim 1 , wherein adjusting the operational parameter includes adjusting a sort delay.
13 . The system of claim 1 , wherein adjusting the operational parameter includes adjusting a parameter of a purity mask.
14 . A method for calibration of particle sorting in a fluid stream, comprising: delivering a sequence of two or more sortable units from a fluid stream to an inspection zone using a particle delivery device; interrogating the two or more sortable units using an electromagnetic radiation source at the inspection zone; monitoring non-targeted sortable units that are located adjacent in sequence to targeted sortable units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units using a monitoring system; sorting, using a sorter downstream of the electromagnetic radiation source, the adjacent non-targeted sortable units to a single output pathway monitored by the monitoring system using a sort logic, the single output pathway associated with a flow of the adjacent non-targeted sortable units; directing the targeted sortable units away from the single output pathway; interrogating, by the monitoring system, the adjacent non-targeted sortable units; and adjusting an operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units by the monitoring system.
15 . The method of claim 14 , further comprising: sweeping a sort delay in the sort logic while interrogating the adjacent non-targeted sortable units; and selecting a value for the sort delay for which a detected intensity from the adjacent non-targeted sortable units is minimum.
16 . The method of claim 15 , wherein selecting the value for the sort delay further comprises identifying the minimum detected intensity bracketed by two peak intensity values that are larger than a background intensity value.
17 . The method of claim 14 , wherein adjusting the sort logic includes adjusting a parameter of a purity mask.
18 . A non-transitory computer-readable medium holding computing device-executable instructions for calibrating particle sorting in a fluid stream, the instructions when executed causing at least one computing device to: deliver a sequence of two or more sortable units from a fluid stream to an inspection zone using a particle delivery device operatively connected to the at least one computing device; interrogate the two or more sortable units using an electromagnetic radiation source at the inspection zone; monitor non-targeted sortable units that are located adjacent in sequence to targeted sortable units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units using a monitoring system; sort, using a sorter downstream of the electromagnetic radiation source, the adjacent non-targeted sortable units to a single output pathway monitored by the monitoring system using a sort logic, the single output pathway associated with a flow of the adjacent non-targeted sortable units; direct the targeted sortable units away from the single output pathway; interrogate, by the monitoring system, the adjacent non-targeted sortable units; and adjust an operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units by the monitoring system.
19 . The non-transitory computer-readable medium of claim 18 , further comprising instructions that, when executed, cause the at least one computing device to: sweep a sort delay in the sort logic while interrogating the adjacent non-targeted sortable units; and select a value for the sort delay for which a detected intensity from the adjacent non-targeted sortable units is minimum.
20 . The non-transitory computer-readable medium of claim 19 , wherein the instructions to select the value for the sort delay further comprise instructions to identify the minimum detected intensity bracketed by two peak intensity values that are larger than a background intensity value.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 17/706,432 filed on Mar. 28, 2022, which claims priority to U.S. Provisional Application No. 63/166,635, filed Mar. 26, 2021, and the entire contents of the identified applications are incorporated herein by reference. BACKGROUND Particle sorting systems can separate particles of interest from a general population of particles flowing in a fluid stream. Such systems can operate on a “detect-decide-deflect” principle wherein particles in the stream are detected, a decision is made as to whether the particle is a particle of interest, and the particles of interest are deflected into one or more keep paths. Operational parameters of a sorting system can be adjusted to change statistical outcomes such as particle recovery and purity. SUMMARY A system for sorting particles flowing in a fluid stream is provided. The system includes a particle delivery device for delivering a sequence of two or more sortable units from a fluid stream to an inspection zone. The system also includes an electromagnetic radiation source for interrogating the two or more sortable units at the inspection zone. The system also includes a sorter downstream of the electromagnetic radiation source to sort the two or more sortable units based on a characteristic thereof using a sort logic. The system also includes a monitoring system downstream of the sorter to interrogate non-targeted sortable units that were adjacent to targeted sortable units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units. The system also includes a processing unit operatively connected to the sorter and the monitoring system, the processing unit configured to execute instructions to adjust an operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units. A method for calibration of particle sorting in a fluid stream is provided. The method includes delivering a sequence of two or more sortable units from a fluid stream to an inspection zone using a particle delivery device. The method also includes interrogating the two or more sortable units using an electromagnetic radiation source at the inspection zone. The method also includes sorting, using a sorter downstream of the electromagnetic radiation source, the two or more sortable units based on a characteristic thereof using a sort logic. The method also includes interrogating non-targeted sortable units (containing no detectable particles of interest) that were adjacent to targeted sortable units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units using a monitoring system. The method also includes adjusting an operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units. A non-transitory computer-readable medium is provided that holds computing device-executable instructions for calibrating particle sorting in a fluid stream. When executed, the instructions cause at least one computing device to deliver a sequence of two or more sortable units from a fluid stream to an inspection zone using a particle delivery device operatively connected to the at least one computing device. The instructions further cause the at least one computing device to interrogate the two or more sortable units using an electromagnetic radiation source at the inspection zone. The instructions further cause the at least one computing device to sort, using a sorter downstream of the electromagnetic radiation source, the two or more sortable units based on a characteristic thereof using a sort logic. The instructions further cause the at least one computing device to interrogate non-targeted sortable units that were adjacent to targeted units that are predicted to include one or more particles having a predetermined characteristic of interest in the sequence of sortable units using a monitoring system. The instructions further cause the at least one computing device to adjust an operational parameter of the sort logic based upon a result of the interrogation of the adjacent non-targeted sortable units. BRIEF DESCRIPTION OF THE DRAWINGS The skilled artisan will understand that the drawings are primarily for illustrative purposes and are not intended to limit the scope of the subject matter taught herein. The drawings are not necessarily to scale; in some instances, various aspects of the subject matter disclosed herein may be exaggerated or enlarged in the drawings to facilitate an understanding of different features. In the drawings, like reference characters generally refer to like features (e.g., functionally similar or structurally similar elements). The foregoing and other features and advantages provided by the present disclosure will be m