# US 11,994,459 B2 · Adaptive sorting for particle analyzers

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- Number: US 11,994,459 B2
- Document ID: US11994459B2
- Status: Granted
- Kind: B2
- Application number: 18/130,571
- Filed: 2023-04-04
- Published: 2023-08-03
- Granted: 2024-05-28
- Earliest claimed: 2018-10-17
- Assignees: Becton, Dickinson and Company
- Applicants: Becton, Dickinson and Company
- Inventors: Jonathan Lin; Joseph T. Trotter; Keegan Owsley
- Web page: https://patentgrep.com/patent/US11994459B2

## CPC

- G01N 15/1459: {the analysis being performed on a sample stream}
- B07C 5/3425: {of granular material, e.g. ore particles, grain (investigation moving fluids or granular solids using optical means G01N21/85)}
- B07C 5/36: Sorting apparatus characterised by the means used for distribution {(sorting according to destination B07C3/003, B07C3/02)}
- B07C 5/361: {Processing or control devices therefor, e.g. escort memory}
- G01N 15/1425: {using an analyser being characterised by its control arrangement}
- G01N 15/1434: Optical arrangements
- G06F 18/285: {Selection of pattern recognition techniques, e.g. of classifiers in a multi-classifier system}
- G06V 10/87: {using selection of the recognition techniques, e.g. of a classifier in a multiple classifier system}
- G06V 20/695: {Preprocessing, e.g. image segmentation}
- G06V 20/698: {Matching; Classification}
- G16C 20/20: Identification of molecular entities, parts thereof or of chemical compositions
- G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties
- G01N 2015/1006: {for cytology}
- G01N 2015/1477: {Multiparameters}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B07C: POSTAL SORTING; SORTING INDIVIDUAL ARTICLES, OR BULK MATERIAL FIT TO BE SORTED PIECE-MEAL, e.g. BY PICKING (specially adapted for a specific purpose covered by another class, see the relevant place, e.g. A43D33/06, B23Q7/12)
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- G06V: IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

A cell sorting system that automatically generates a sorting strategy based on examples of target events provided by an operator. The target events can be selected using measurements ranging from traditional flow cytometry measurements to derived measurements that are computationally expensive to complex measurements such as images.

## Claims

### Claim 1

A computer-implemented method comprising:
under control of one or more processing devices,
receiving, from a communication device, a reference sorting criteria for a sample with a particle analyzer;
identifying candidate event classifiers for the sample based at least in part on the reference sorting criteria;
generating a sorting strategy, the sorting strategy including at least one event classifier from the candidate event classifiers; and
configuring the particle analyzer to classify a particle for the sample based at least in part on the sorting strategy.

### Claim 2 (depends on 1)

The computer-implemented method of claim 1, wherein the reference sorting criteria comprises gate information identifying a range of measurements for classifying the particle.

### Claim 3 (depends on 1)

The computer-implemented method of claim 1, wherein the reference sorting criteria comprises an image showing a reference particle to be collected from the sample.

### Claim 4 (depends on 1)

The computer-implemented method of claim 1, further comprising:
transmitting a sorter configuration to the particle analyzer, wherein the sorter configuration represents the sorting strategy; and
adjusting sorting circuitry based at least in part on the sorter configuration.

### Claim 5 (depends on 4)

The computer-implemented method of claim 4, wherein the sorting circuitry comprises a field programmable gate array.

### Claim 6 (depends on 1)

The computer-implemented method of claim 1, further comprising receiving a multidimensional measurement from the particle analyzer, wherein the multidimensional measurement comprises a measurement of light emitted fluorescently by the particle.

### Claim 7 (depends on 6)

The computer-implemented method of claim 6, wherein the light emitted fluorescently by the particle comprises light emitted fluorescently by antibodies bound to the particle.

### Claim 8 (depends on 1)

The computer-implemented method of claim 1, further comprising generating a metric indicating an accuracy of the sorting strategy,
wherein the metric comprises an f-measure of the sorting strategy,
wherein a precision component of the f-measure represents purity for sorting of the sample according to the sorting strategy, and
wherein a recall component of the f-measure represents yield for sorting of the sample according to the sorting strategy.

### Claim 9 (depends on 1)

The computer-implemented method of claim 1, further comprising:
storing, in a data store, the candidate event classifiers, wherein the candidate event classifiers comprise at least two of:
(a) a computational sorting classifier including: a scoring and relevant target or off-target score, wherein a score for a particle measurement is compared with the relevant target or off-target score for sorting;
(b) a transformation to convert one or more measurements for a particle into an approximate measurement for the particle;
(c) a parameter projection to convert a population represented by the reference sorting criteria from a first parameter space that is not sortable into a second parameter space that can be sorted; and
(d) a feature extraction to generate a vector features from images or high-dimensional measurements, wherein the vector of features are used to classify a particle.

### Claim 10 (depends on 1)

The computer-implemented method of claim 1, further comprising:
receiving, from the particle analyzer, a hardware identifier indicating sorting circuitry implemented in the particle analyzer,
wherein identifying the candidate event classifiers is further based at least in part on the hardware identifier.

### Claim 11 (depends on 1)

The computer-implemented method of claim 1, wherein configuring the particle analyzer comprises:
configuring the particle analyzer to dynamically process event data using a parametric machine learning transformation.

### Claim 12 (depends on 1)

A non-transitory computer-readable medium having stored thereon instructions which when executed perform the method of claim 1.

### Claim 13 (depends on 1)

An apparatus comprising a processor, wherein the processor is configured to perform the method of claim 1.

### Claim 14

A system comprising:
one or more processing devices; and
a computer-readable storage medium comprising instructions that, when executed by the one or more processing devices, causes the system to,
receive, from a communication device, a reference sorting criteria for a sample with a particle analyzer;
identify candidate event classifiers for the sample based at least in part on the reference sorting criteria;
generate a sorting strategy, the sorting strategy including at least one event classifier from the candidate event classifiers;
generate a control signal to adjust an operational state for an analytical means included in the particle analyzer, wherein the operational state is based at least in part on the sorting strategy; and
transmit the control signal to the analytical means to achieve the operational state.

### Claim 15 (depends on 14)

The system of claim 14,
wherein the analytical means comprises sorting electronics communicatively coupled to a deflection plate,
wherein particle analyzer is further configured to identify a target vessel for a particle based at least in part on a measurement corresponding the sorting strategy for the target vessel, and
wherein adjusting the operational state comprises application of a charge via a deflector plate to direct the particle into a target vessel.

### Claim 16 (depends on 15)

The system of claim 15, where the analytical means comprises a fluidics system, and wherein adjusting the operational state comprises regulating a pressure applied during an experiment for analyzing the sample.
