EP-4739996-A1 - SYSTEMS AND METHODS FOR OFF-AXIS BUBBLE DETECTION

Abstract

A detection system that operates with reduced sample waste and dead volume, the system including: a module configured to introduce a sample spacer into a sample; at least one light source, wherein the light source illuminates the sample spacer and the sample, wherein illumination of the sample spacer produces scattered light; and a detection device configured to initiate acquisition of data related to the sample in response to scattered light detected by the detection device.

Inventors

• QUIGLEY, Daniel
• FOX, Daniel Nelson
• JOHNSON, KEITH

Assignees

• Life Technologies Corporation

Dates

Publication Date

20260513

Application Date

20240802

Claims (20)

1. 1. A detection system, comprising: a module configured to introduce a sample spacer into a sample; at least one light source, wherein the light source illuminates the sample spacer and the sample, wherein illumination of the sample spacer produces scattered light; and a detection device configured to initiate acquisition of data related to the sample in response to scattered light associated with the sample spacer detected by the detection device.
2. 2. The detection system of claim 1, further comprising an acquisition train configured to: receive a signal from the detection device and. in response to the signal, begin acquisition of data associated with the sample.
3. 3. The detection system of any one of claims 1 or 2, wherein the acquisition train is further configured to begin acquisition of data following the signal attaining a specified value.
4. 4. The detection system of claim 3, wherein the acquisition train is further configured to begin acquisition of data at a first time following the signal attaining the specified value.
5. 5. The detection system of claim 4, wherein the first time comprises a delay, the delay optionally based at least in part on at least one of a volume of the sample or a flow rate at which the sample is communicated through a flow cell.
6. 6. The detection system of any one of claims 1 or 2, wherein the acquisition train is further configured to process the signal to generate a processed signal and begin the acquisition of data following the processed signal differing from a specified value for a specified time period.
7. 7. The detection system of claim 6, wherein the acquisition train is further configured to process the signal to generate a processed signal and begin the acquisition of data at a first time following the processed signal differing from the specified value for the specified time period.
8. 8. The detection system of claim 7, wherein the first time comprises a delay, the delay optionally based at least in part on at least one of a volume of the sample or a flow rate at which the sample is communicated through a flow cell.
9. 9. The detection system of any one of claims 1 or 2, wherein the acquisition train is further configured to cease the acquisition of data in response to at least one of a volume of the sample analyzed, a length of time, a number of events, or receipt from the detection device of a signal associated with scattered light from an additional sample spacer.
10. 10. The detection system of claim 1, wherein the sample spacer comprises a volume of from 0.5 pl to 4.0 pl.
11. 11. The detection system of claim 1, wherein the sample spacer comprises a volume of from 0.5 pl to 2 pl.
12. 12. The detection system of claim 1, wherein the light source comprises at least one of a 405 nm or a 488 nm laser.
13. 13. The detection system of claim 1, wherein the module comprises at least one of a valve, a pump, an injector, a cavitation apparatus, a heat source, or a gas permeable membrane.
14. 14. The detection system of claim 1, wherein the detection device comprises at least one sample spacer detector configured to detect the scattered light associated with the sample spacer, and wherein the detection device further comprises at least one sample detector configured to acquire data related to the sample.
15. 15. The detection system of claim 1. wherein the detection device comprises one detection device, wherein the one detection device is configured to detect the scattered light associated with the sample spacer and further configured to acquire data related to the sample.
16. 16. A system, comprising: a flow 7 cell; a module configured to introduce a sample spacer into a sample; at least one light source, wherein the light source illuminates the sample spacer and the sample, wherein illumination of the sample spacer produces scattered light; and a detection device configured to initiate acquisition of data associated with the sample in response to scattered light associated with the sample spacer detected by the detection device.
17. 17. The system of claim 16, further comprising an acquisition train configured to: receive a signal from the detection device and. in response to the signal, begin acquisition of data associated with the sample.
18. 18. The system of any one of claims 16 or 17, wherein the acquisition train is further configured to begin acquisition of data following the signal attaining a specified value.
19. 19. The system of claim 18, wherein the acquisition train is further configured to begin acquisition of data at a first time following the signal attaining the specified value.
20. 20. The system of claim 19, wherein the first time comprises a delay, the delay optionally based at least in part on at least one of a volume of the sample or a flow rate at which the sample is communicated through the flow cell.

Description

SYSTEMS AND METHODS FOR OFF-AXIS BUBBLE DETECTION RELATED APPLICATIONS [0001] The present application claims priority to and the benefit of United States patent application no. 63/517,417, "Systems And Methods For Off-Axis Bubble Detection" (filed August 3, 2023). All foregoing applications are incorporated herein by reference in their entireties for any and all purposes. TECHNICAL FIELD [0002] The present disclosure relates to the field of optical sample analysis. BACKGROUND [0003] Detection and characterization of particles, whether biological, organic, or inorganic, is essential in a broad range of fields, including clinical and environmental fields. Sample particles may be analyzed to determine various characteristics associated with the particles, which characteristics can include physical properties, optical properties, electronic properties, and the like. Samples can be expensive to acquire, time consuming to prepare, or otherwise difficult to gather in sufficient quantities to test. Improving sample accuracy and precision while minimizing sample waste is desirable, as is improving sample throughput. [0004] Existing methods of particle characterization, however, have certain deficiencies, as existing methods often require tradeoffs between speed, accuracy, precision, and minimizing sample waste. As one example, increasing sample accuracy in a given method can result in reduced throughput speed. [0005] In particular, operation of existing sample testing systems and methods often also entails a quantity7 of wasted sample, which wasted sample can be termed “dead volume.” Dead volume can result when the configuration of a system is such that when an amount of sample is passed through the system, data is acquired from only a portion of that amount of sample, thereby wasting some of the sample and also reducing the overall amount of data that is obtained from a given sample run. Given the time and effort needed to prepare sample for testing - which preparation can involve costly and time-consuming incubation steps - there is a long-felt need for approaches that operate using less dead volume, as such approaches would analyze a higher proportion of sample, thereby obtaining increased data from a given sample run and allowing for more robust conclusions to be drawn from those increased data. [0006] Some attempts to address these shortcomings involve incorporating a spacer into a fluid sample to delineate between segments of sample. Introducing a spacer into a fluid can, how ever, have a negative impact on the sample collection process. For example, a bubble included in a fluid sample can produce inaccurate test results, as a bubble can interrupt a contiguous fluid sample and thereby present an impediment to collecting accurate data from the sample. For this reason, systems and methods known in the art are often constructed to minimize the possibility of the inclusion of a bubble, or other spacer, in a sample fluid. Accordingly, there is a long-felt need in the field for improved methods of sample detection. SUMMARY [0007] In meeting the described challenges, the present disclosure provides, inter alia, the inclusion of a sample spacer, for example a bubble, in a sample detection system. As one example, a bubble can be incorporated into the leading edge of a sample, and a detection system may be configured to detect the bubble transiting the detection system. In this way, the detection system can determine, with a greater degree of accuracy than what is known in the art, when a sample is passing through a detection system, based at least in part on detecting the sample spacer. Traditionally, bubbles in a sample are considered undesirable, as bubbles are considered detrimental to sample precision and accuracy. The disclosed technology, however, utilizes bubbles in a manner contrary to the conventional wisdom. Rather than seeking to eliminate bubbles as is done in existing approaches, the disclosed technology instead makes use of bubbles, as bubbles in the disclosed technology can be used as sample spacers, which sample spacers in turn can help improve sample precision and accuracy. Hence, intentional introduction of a sample spacer in a sample can be used to reduce dead volume and thereby increase the acquisition of useful data in a system. [0008] In one aspect, the present disclosure provides a detection system, comprising: a module configured to introduce a sample spacer into a sample; at least one light source, wherein the light source illuminates the sample spacer and the sample, wherein illumination of the sample spacer produces scattered light; and a detection device configured to initiate acquisition of data related to the sample in response to scattered light associated with the sample spacer detected by the detection device. [0009] Also provided is a system, comprising: a flow cell; a module configured to introduce a sample spacer into a sample; at least one light source, wherein the light source