Automated and accurate drop delay for flow cytometry
US-9696257-B2 · Jul 4, 2017 · US
US10481069B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10481069-B2 |
| Application number | US-201213342756-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jan 3, 2012 |
| Priority date | Jan 3, 2011 |
| Publication date | Nov 19, 2019 |
| Grant date | Nov 19, 2019 |
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Particle processing systems and methods utilize a sort monitoring system to monitor an operational characteristic for a particle sorting system. The operational characteristic may be related to the performance and operation of a sorter or a group of sorters in the particle sorting system. The operational characteristic may be monitored based on monitoring particles for an output of a sorter or of a group of sorters. Operational characteristics which may be monitored include sort error, sort fraction, yield, purity and recovery percentage. The sort monitoring system may evaluate the monitored operational characteristic, for example, as related to sort performance, and take an action, for example, a corrective action or a notifying action, based on the evaluation of the operational characteristic.
Opening claim text (preview).
What is claimed: 1. A particle processing system comprising: a microfluidic sort module having a branched flow-channel defined in a substrate to receive a stream of particles, the branched flow-channel including a flow-path that branches at a branch point into a first output branch channel and a second output branch channel, the microfluidic sort module further having a particle sorter operable to selectively sort particles between the first output branch channel and the second output branch channel; a first sensor system optically coupled to the flow-path upstream of the branch point having focusing optics and a first optical sensor to sense a particle characteristic of a particle flowing through the flow path to control a sorting operation of the microfluidic sort module; a capillary tube fluidically coupled to one of the first output branch channel or the second output branch channel; and a sort monitoring system having a second sensor system optically coupled to the capillary tube to monitor a performance of the sorting operation by detecting and collecting particle data that characterizes individual particles downstream of the particle sorter using focusing optics to direct light through the capillary tube and onto a second optical sensor to determine a statistically-based characteristic of a composition of a sorted sample from the data collected from the individual particles detected downstream of the particle sorter, and wherein the sort monitoring system is configured to real-time evaluate the statistically-based characteristic of the composition of the sorted sample. 2. The particle processing system of claim 1 , further comprising a programmable controller responsive to an output of the sort monitoring system and configured to control one or more operations of the particle processing system. 3. The particle processing system of claim 1 , further comprising a programmable controller configured to adjust a flow rate of the stream of suspended particles as the stream continues to flow through the particle sorter based on an evaluation of the statistically-based characteristic of the composition of the sorted sample. 4. The particle processing system of claim 1 , wherein the sort monitoring system is configured to track a particle at different locations in the particle processing system. 5. The particle processing system of claim 1 , further comprising a programmable controller configured to increase particle throughput when the evaluation of the statistically-based characteristic of the composition of the sorted sample relative to a predetermined sort performance criteria shows that the particle processing system is over performing. 6. The particle processing system of claim 1 , wherein the sort monitoring system is configured to real-time evaluate the performance of the sorting operation based on one or more sort parameters, and wherein the one or more sort parameters include a baseline event rate or a baseline margin of error for one of the output branch channels. 7. The particle processing system of claim 1 , wherein the microfluidic sort module includes a plurality of the branched channels and a plurality of the particle sorters for sorting particles within the branched channels, wherein the sort monitoring system includes a monitor sensor configured to monitor a statistically-based operational characteristic of a sorted sample, and wherein the sort monitoring system is configured to real-time evaluate a collective performance of the plurality of particle sorters. 8. The particle processing system of claim 7 , wherein the monitor sensor is configured to detect a presence or an absence of particles in a first monitor region downstream of at least two of the sorters. 9. The particle processing system of claim 7 , wherein the monitor sensor is configured to monitor a merged output of at least two of the sorters. 10. The particle processing system of claim 7 , wherein the monitor sensor is configured to monitor an individual output of one of the sorters. 11. The particle processing system of claim 10 , wherein the monitoring system further includes a second monitor sensor configured to monitor a merged output of at least two of the sorters. 12. The particle processing system of claim 7 , wherein a first of the sorters is upstream of a second of the sorters and the monitor sensor is configured to detect a presence or absence of particles at monitor region downstream of both the first and second of the sorters. 13. The particle processing system of claim 7 , wherein the monitor sensor is configured to detect a presence or absence particles at a monitor region downstream of a first of the sorters and upstream of a second of the sorters. 14. The particle processing system of claim 13 , wherein the monitoring system further comprises a second monitor sensor configured to detect a presence or absence of particles at a second monitor region downstream of the second of the sorters. 15. The particle processing system of claim 7 , wherein the operational characteristic is related to a collective performance of a plurality of the sorters. 16. The particle processing system of claim 7 , wherein the operational characteristic is related to an individual performance of one of the sorters. 17. The particle processing system of claim 7 , further comprising a programmable microprocessor for evaluating the operational characteristic and taking an action based thereon. 18. A method for processing particles flowing through a particle sorting system, the method comprising: receiving a stream of particles in a branched flow-channel defined in a substrate of the particle sorting system, the branched flow-channel including a flow-path that branches at a branch point into a first output branch channel and a second output branch channel; detecting a particle characteristic of one or more of the particles in the stream of particles using a first sensor system optically coupled to the flow-path having focusing optics and a first optical sensor; using a particle sorter to selectively sort the particles in the stream of suspended particles between the first output branch channel and the second output branch channel based on the detected particle characteristic; flowing particles from one of the first output branch channel or the second output branch through a capillary tube fluidically coupled to the substrate; monitoring a sorting operation of the particle sorter using a second sensor system having focusing optics to direct light through the capillary tube and onto a second optical sensor to detect and collect particle data that characterizes individual particles downstream of the particle sorter to determine a statistically-based characteristic of a composition of a sorted sample from the data collected from the individual particles detected downstream of the particle sorter; and evaluating the statistically-based characteristic of the composition of the sorted sample in real-time relative to a predetermined sort performance criteria. 19. The method of claim 18 , further comprising controlling the operation of the particle sorting system based on the evaluated statistically-based characteristic of the composition of the sorted sample. 20. The method of claim 18 , further comprising adjusting a flow rate of the stream of suspended particles as the stream continues to flow through the particle sorting system based on an evaluation of the statistically-based characteristic of the composition of the sorted sample. 21.
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