EP-3586104-B1 - LIGHT DETECTION SYSTEMS AND METHODS FOR USING THEREOF

Inventors

• CAO, JIANYING
• WU, Austin
• DO, David Thao
• PETERSEN, TIMOTHY WAYNE

Dates

Publication Date

20260513

Application Date

20180212

Claims (12)

1. A light detection system for detecting light emitted by a sample in a flow stream of a flow cytometer comprising: a first photodetector array comprising: first and second photodetectors, and a first beam splitter configured to propagate light to each of the photodetectors; a second photodetector array comprising: third and fourth photodetectors, and a second beam splitter configured to propagate light to each of the photodetectors; wherein the first photodetector array and the second photodetector array each are concentrically arranged around an optical adjustment component; and the optical adjustment component positioned in an optical path between the first photodetector array and the second photodetector array, wherein the optical adjustment component comprises a collimator that collimates light propagated between the first photodetector array to the second photodetector array.
2. The light detection system according to claim 1, wherein the optical adjustment component comprises a beam splitter.
3. The light detection system according to claim 1 or 2, wherein the optical adjustment component comprises a wavelength separator.
4. The light detection system according to any one of claims 1-3, wherein the optical adjustment component comprises a dichroic mirror.
5. The light detection system according to any one of claims 1-4, wherein two or more optical adjustment components are positioned between the first photodetector array and the second photodetector array.
6. The light detection system according to claim 5, wherein the optical adjustment component comprises a dichroic mirror and a collimator.
7. The light detection system according to any one of claims 1-6, wherein the system further comprises: a third photodetector array; and an optical adjustment component positioned in an optical path between the second photodetector array and the third photodetector array.
8. The light detection system according to any one of claims 1-7, wherein the photodetector arrays are positioned along a single axis or along more than one axis.
9. The light detection system according to any one of claims 1-8, wherein the photodetector arrays have a polygonal configuration in the light detection system.
10. The light detection system according to any one of claims 1-9, wherein each photodetector array comprises aligners, such that a complete optical path is formed between the photodetector arrays when the aligners of the first photodetector array are coupled to the aligners of the second photodetector array.
11. A system comprising: a light source; and a light detection system according to any one of claims 1 to 10.
12. A method comprising: detecting light from a flow stream with a light detection system according to any one of claims 1 to 10.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to the filing date of United States Provisional Patent Application Serial No. 62/464,282 filed February 27, 2017. INTRODUCTION Light detection is often used to characterize components of a sample (e.g., biological samples), for example when the sample is used in the diagnosis of a disease or medical condition. When a sample is irradiated, light can be scattered by the sample, transmitted through the sample as well as emitted by the sample (e.g., by fluorescence). Variations in the sample components, such as morphologies, absorptivity and the presence of fluorescent labels may cause variations in the light that is scattered, transmitted or emitted by the sample. These variations can be used for characterizing and identifying the presence of components in the sample. To quantify these variations, the light is collected and directed to the surface of a detector. The amount of light that reaches the detector can impact the overall quality of the optical signal outputted by the detector. The amount of light that reaches the detector can be raised by increasing the surface area of the detector or by increasing collection of the light from the sample. One technique that utilizes light detection to characterize the components in a sample is flow cytometry. Using data generated from the detected light, distributions of the components can be recorded and where desired material may be sorted. A flow cytometer typically includes a sample reservoir for receiving a fluid sample, such as a blood sample, and a sheath reservoir containing a sheath fluid. The flow cytometer transports the particles (including cells) in the fluid sample as a cell stream to a flow cell, while also directing the sheath fluid to the flow cell. Within the flow cell, a liquid sheath is formed around the cell stream to impart a substantially uniform velocity on the cell stream. The flow cell hydrodynamically focuses the cells within the stream to pass through the center of a light source in a flow cell. Light from the light source can be detected as scatter or by transmission spectroscopy or can be absorbed by one or more components in the sample and re-emitted as luminescence. The abstract of US 2003048539 A1 states: ' An optical instrument using a plurality of lasers of different colors with parallel, closely spaced beams to stimulate scattering and fluorescence from fluorescent biological particulate matter, including cells and large molecules. A large numerical aperture objective lens collects fluorescent light while maintaining spatial separation of light stimulated by the different sources. The collected light is imaged into a plurality of fibers, one fiber associated with each optical source, which conducts light to a plurality of arrays of detectors, with each array associated with light from one of the fibers and one of the lasers. A detector array has up to ten detectors arranged to separate and measure colors within relatively narrow bands by decimation of light arriving in a fiber. A large number of detectors is mounted in a compact polygonal arrangement by using reflective transfer legs from multiple beam splitters where the transfer legs arise from a polygonal arrangement of beam splitters in a circumference within the circumferential arrangement of detectors.' The abstract of US 2012001083 A1 states: ' Demultiplexing systems and methods are discussed which may be small and accurate without moving parts. In some cases, demultiplexing embodiments may include optical filter cavities that include filter baffles and support baffles which may be configured to minimize stray light signal detection and crosstalk. Some of the demultiplexing assembly embodiments may also be configured to efficiently detect U.V. light signals and at least partially compensate for variations in detector responsivity as a function of light signal wavelength.' The abstract of WO2007/100723A2 refers to an optical system for a flow cytometer including a flow channel with an interrogation zone, and an illumination source that impinges the flow channel in the interrogation zone from a particular direction. SUMMARY The present disclosure provides a light detection system for detecting light emitted by a sample in a flow stream of a flow cytometer according to claim 1, and a system and method, using said light detection system, according to claims 11 and 12, respectively. Aspects of the present disclosure include light detection systems having two or more photodetector arrays. Systems according to certain embodiments include a first photodetector array in optical communication with a second photodetector array, each photodetector array having two or more photodetectors (e.g., photomultiplier tubes) and an optical adjustment component positioned in an optical path between the photodetector arrays. In some embodiments, the optical adjustment component is a collimator that collimates light between phot