High-throughput hyperspectral imaging systems

Patent metadata

Field	Value
Publication number	US-11598725-B2
Application number	US-202217734222-A
Country	US
Kind code	B2
Filing date	May 2, 2022
Priority date	Jan 22, 2018
Publication date	Mar 7, 2023
Grant date	Mar 7, 2023

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 and direct the excitation light through a sample such that the excitation light causes the sample to emit fluorescence light, wherein the excitation light source comprises:
a light source, and
a lens configured to receive light from the light source and generate an excitation stripe;

an objective that is configured to receive the fluorescence light from the sample and generate imaged fluorescence light;
a slit, positioned to receive the imaged fluorescence light and configured to transmit the imaged fluorescence light;
a channel separator configured to receive fluorescence light transmitted through the slit and separate the fluorescence light into a plurality of spatially dispersed spectral channels, wherein the channel separator comprises:
a first collimating lens,
a second collimating lens, and
one or more dispersion optics between the first and second collimating lenses; and

a sensor that is configured to receive the plurality of spatially dispersed spectral channels from the channel separator.

2. The system according to claim 1 , wherein the slit comprises a patterned layer comprising a transmitting region and one or more reflecting or absorbing regions, wherein the transmitting region is configured to transmit the imaged fluorescence light.

3. The system according to claim 1 , wherein the lens configured to receive light from the light source and generate the excitation stripe comprises a cylindrical lens.

4. The system according to claim 1 , further comprising a filter configured to block light from the excitation light source from reaching the sensor.

5. The system according to claim 4 , wherein the filter comprises one or more of a single-notch filter, a long-pass filter, or a multi-notch filter.

6. The system according to claim 1 , further comprising one or more tube lenses configured for imaging the fluorescence light together with the objective.

7. The system according to claim 1 , wherein the one or more dispersion optics comprise a plurality of prisms.

8. The system according to claim 1 , wherein the one or more dispersion optics comprise a set of double Amici prisms.

9. The system according to claim 1 , wherein the one or more dispersion optics are adjustable to provide more or less dispersion.

10. The system according to claim 1 , wherein the excitation light source further comprises one or more additional light sources, wherein the lens is configured to receive light from the one or more additional light sources and generate one or more additional excitation stripes, each of the one or more additional excitation stripes causing the sample to emit additional fluorescence light, and wherein the objective is configured to image the additional fluorescence light.

11. A method comprising:
emitting excitation light by an excitation light source, wherein the excitation light source comprises:
a light source, and
a lens configured to receive light from the light source and generate an excitation stripe;

directing the excitation stripe onto a sample such that the excitation stripe causes the sample to emit fluorescence light;
generating imaged fluorescence light from the fluorescence light using an objective;
transmitting the imaged fluorescence light through a slit;
separating, by a channel separator, fluorescence light transmitted through the slit into a plurality of spatially dispersed spectral channels, wherein the channel separator comprises:
a first collimating lens,
a second collimating lens, and
one or more dispersion optics between the first and second collimating lenses; and

receiving, by a sensor, the plurality of spatially dispersed spectral channels from the channel separator.

12. The method according to claim 11 , wherein the slit comprises a patterned layer comprising a transmitting region and one or more reflecting or absorbing regions, wherein the transmitting region is configured to transmit the imaged fluorescence light.

13. The method according to claim 11 , wherein the lens configured to receive light from the light source and generate the excitation stripe comprises a cylindrical lens.

14. The method according to claim 11 , further comprising blocking light from the excitation light source from reaching the sensor using a filter.

15. The method according to claim 14 , wherein the filter comprises one or more of a single-notch filter, a long-pass filter, or a multi-notch filter.

16. The method according to claim 11 , wherein generating imaged fluorescence light from the fluorescence light comprising using one or more tube lenses together with the objective.

17. The method according to claim 11 , wherein the one or more dispersion optics comprise a plurality of prisms.

18. The method according to claim 11 , wherein the one or more dispersion optics comprise a set of double Amici prisms.

19. The method according to claim 11 , wherein the one or more dispersion optics are adjustable to provide more or less dispersion.

20. The method according to claim 11 , wherein the excitation light source further comprises one or more additional light sources, wherein the lens is configured to receive light from the one or more additional light sources and generate one or more additional excitation stripes, each of the one or more additional excitation stripes causing the sample to emit additional fluorescence light, and wherein the objective is configured to image the additional fluorescence light.

Assignees

• Verily Life Sciences Llc

Inventors

• Sinha Supriyo
• Santori Charles
• Conrad Andrew

Classifications

• G01N21/6458

  Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16) · CPC title

• G01N21/64 Primary

  Fluorescence; Phosphorescence · CPC title

• G01J3/0208

  using focussing or collimating elements, e.g. lenses or mirrors; performing aberration correction · CPC title

• G01N2201/0635

  Structured illumination, e.g. with grating · CPC title

• G01J2003/2826

  Multispectral imaging, e.g. filter imaging · CPC title