High-throughput hyperspectral imaging systems

Patent metadata

Field	Value
Publication number	US-11327017-B2
Application number	US-202017062191-A
Country	US
Kind code	B2
Filing date	Oct 2, 2020
Priority date	Jan 22, 2018
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

High-throughput hyperspectral imaging systems are provided. According to an aspect of the invention, a system includes an excitation light source; an objective that is configured to image excitation light onto the sample, such that the excitation light causes the sample to emit fluorescence light; a channel separator that is configured to separate the fluorescence light into a plurality of spatially dispersed spectral channels; and a sensor. The excitation light source includes a light source and a plurality of lenslet arrays. Each of the lenslet arrays is configured to receive light from the light source and to generate a pattern of light, and the patterns of light generated by the lenslet arrays are combined to form the excitation light. The objective is configured to simultaneously image each of the patterns of light to form a plurality of parallel lines or an array of circular spots at different depths of the sample.

First claim

What is claimed is:

1. A system comprising:
an excitation light source that is configured to emit excitation light;
an objective that is configured to receive the excitation light from the excitation light source and image the excitation light onto a sample, such that the excitation light causes the sample to emit fluorescence light;
a channel separator that is configured to receive the fluorescence light from the sample and separate the fluorescence light into a plurality of spatially dispersed spectral channels; and
a sensor that is configured to receive the plurality of spatially dispersed spectral channels from the channel separator,
wherein the excitation light source comprises:
a plurality of light sources, wherein each of the plurality of light sources emits light having a different wavelength;
a dichroic array that is configured to combine light from each of the plurality of light sources; and
a first lenslet array, wherein the first lenslet array is configured to receive light from the dichroic array and to generate a plurality of patterns of light corresponding to the plurality of light sources;

wherein the objective is configured to image the patterns of light to form a plurality of parallel lines at a same depth of the sample or an array of circular spots at a same depth of the sample.

2. The system according to claim 1 , wherein the channel separator comprises:
a reflective layer comprising a plurality of first reflective elements, wherein each first reflective element of the plurality of first reflective elements is configured to reflect a first portion of the fluorescence light that is generated by a first pattern of light of the patterns of light;
a patterned layer that is configured to transmit a second portion of the fluorescence light that is generated by a second pattern of light of the patterns of light;
first dispersion optics that are configured to receive the first portion of the fluorescence light from the reflective layer and to spatially disperse spectral components of the first portion of the fluorescence light; and
second dispersion optics that are configured to receive the second portion of the fluorescence light from the reflective layer and to spatially disperse spectral components of the second portion of the fluorescence light.

3. The system according to claim 1 , wherein the channel separator comprises:
a second lenslet array that is configured to focus the fluorescence light; and
dispersion optics that are configured to receive the fluorescence light from the second lenslet array and to spatially disperse spectral components of the fluorescence light;
wherein the second lenslet array comprises a plurality of arrays of lenslets that are configured to receive the fluorescence light as a plurality of parallel lines or as an array of circular spots.

4. The system according to claim 1 , wherein the channel separator comprises:
dispersion optics that are configured to spatially disperse spectral components of the fluorescence light; and
a second lenslet array that is configured to receive the fluorescence light from the dispersion optics and to focus the fluorescence light;
wherein the second lenslet array comprises a plurality of arrays of lenslets that are configured to receive the fluorescence light as a plurality of parallel lines or as an array of circular spots.

5. The system according to claim 1 , further comprising a dichroic beamsplitter that is configured to reflect the excitation light from the excitation light source toward the objective, and to transmit the fluorescence light from the sample toward the channel separator.

6. The system according to claim 5 , wherein a transmission spectrum of the dichroic beamsplitter comprises a plurality of notches that coincide with the different wavelengths from the light sources.

7. The system according to claim 1 , wherein the objective is configured to image the patterns of light simultaneously.

8. The system of claim 1 , wherein the dichroic array comprises a plurality of dichroic mirrors, wherein each of the plurality of dichroic mirrors is configured to receive light from a respective one of the plurality of light sources.

9. The system of claim 1 , wherein the excitation light source further comprises a collimator that is configured to collimate light from the dichroic array.

10. The system of claim 9 , wherein the excitation light source further comprises a dispersive element that is configured to disperse light from the collimator.

11. A method comprising:
emitting excitation light by an excitation light source;
receiving, by an objective, the excitation light from the excitation light source;
imaging, by the objective, the excitation light onto a sample, such that the excitation light causes the sample to emit fluorescence light;
receiving, by a channel separator, the fluorescence light from the sample;
separating, by the channel separator, the fluorescence light into a plurality of spatially dispersed spectral channels; and
receiving, by a sensor, the plurality of spatially dispersed spectral channels from the channel separator,
wherein emitting the excitation light by the excitation light source comprises:
emitting light having a different wavelength by each of a plurality of light sources;
combining, by a dichroic array, light from each of the plurality of light sources; and
receiving, by a first lenslet array, light from the dichroic array; and
generating, by the first lenslet array, a plurality of patterns of light corresponding to the plurality of light sources, and

wherein the objective images the patterns of light to form a plurality of parallel lines at a same depth of the sample or an array of circular spots at a same depth of the sample.

12. The method according to claim 11 , wherein the channel separator comprises:
a reflective layer comprising a plurality of first reflective elements, wherein each first reflective element of the plurality of first reflective elements reflects a first portion of the fluorescence light that is generated by a first pattern of light of the patterns of light;
a patterned layer that transmits a second portion of the fluorescence light that is generated by a second pattern of light of the patterns of light;
first dispersion optics that receive the first portion of the fluorescence light from the reflective layer and spatially disperse spectral components of the first portion of the fluorescence light; and
second dispersion optics that receive the second portion of the fluorescence light from the reflective layer and spatially disperse spectral components of the second portion of the fluorescence light.

13. The method according to claim 11 , wherein the channel separator comprises:
a second lenslet array that focuses the fluorescence light; and
dispersion optics that receive the fluorescence light from the second lenslet array and spatially disperse spectral components of the fluorescence light;
wherein the second lenslet array comprises a plurality of arrays of lenslets that receive the fluorescence light as a plurality of parallel lines or as an array of circular spots.

14. The method according to claim 11 , wherein the channel separator comprises:
dispersion optics that spatially disperse spectral components of the fluorescence light; and
a second lenslet array that receives the fluorescence light from the dispersion optics and focuses the fluorescence light;
wherein the second lenslet array comprises a plurality of arrays of lenslets that receive the fluorescence light as a plurality of parallel lines or as an array of circular spots.

Assignees

• Verily Life Sciences Llc

Inventors

• Sinha Supriyo
• Santori Charles
• Conrad Andrew

Classifications

• G01N21/6486

  Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence) · CPC title

• G01N21/64 Primary

  Fluorescence; Phosphorescence · CPC title

• G01J3/4406

  Fluorescence spectrometry · CPC title

• G01N21/6456 Primary

  Spatial resolved fluorescence measurements; Imaging · CPC title

• G02B21/361

  Optical details, e.g. image relay to the camera or image sensor (G02B21/364 takes precedence; illumination details G02B21/06 and subgroups) · CPC title