High-throughput hyperspectral imaging with superior resolution and optical sectioning

Patent metadata

Field	Value
Publication number	US-9581797-B2
Application number	US-201615180301-A
Country	US
Kind code	B2
Filing date	Jun 13, 2016
Priority date	Jan 12, 2015
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

An imaging system includes a light source configured to illuminate a target and a camera configured to image light responsively emitted from the target and reflected from a spatial light modulator (SLM). The imaging system is configured to generate high-resolution, hyperspectral images of the target. The SLM includes a refractive layer that is chromatically dispersive and that has a refractive index that is controllable. The refractive index of the refractive layer can be controlled to vary according to a gradient such that light reflected from the SLM is chromatically dispersed and spectrographic information about the target can be captured using the camera. Such a system could be operated confocally, e.g., by incorporating a micromirror device configured to control a spatial pattern of illumination of the target and to modulate the transmission of light from the target to the camera via the SLM according to a corresponding spatial pattern.

First claim

What is claimed is:

1. A system comprising:
a light source;
a first camera, wherein the first camera comprises a plurality of light-sensitive elements disposed on a focal surface of the first camera;
a spatial light modulator, wherein the spatial light modulator comprises a reflective layer disposed beneath a refractive layer, wherein the refractive layer has a refractive index that varies spatially across the spatial light modulator, and wherein the spatial variation of the refractive index is electronically controllable; and
an optical system, wherein the optical system optically couples (i) the light source to a target, (ii) the target to the spatial light modulator, and (iii) the spatial light modulator to the first camera.

2. The system of claim 1 , wherein the refractive layer has a refractive index that varies substantially linearly with wavelength for wavelengths within a specified range of wavelengths.

3. The system of claim 1 , wherein the target contains a fluorophore, and wherein the light source emits light at an excitation wavelength of the fluorophore.

4. The system of claim 1 , wherein the optical system optically couples the target to the spatial light modulator and the spatial light modulator to the camera such that the focal surface of the camera is conjugate to a focal surface passing through the target.

5. The system of claim 1 , further comprising:
a micromirror device, wherein the micromirror device comprises a substantially planar array of actuatable mirrors disposed on a surface, wherein respective angles of the actuatable mirrors relative to the surface are electronically controllable,
wherein the optical system optically couples the light source to the target via reflection from a first set of one or more of the actuatable mirrors, and wherein the optical system optically couples the target to the spatial light modulator via reflection from the first set of one or more actuatable mirrors, and
wherein the one or more actuatable mirrors in the first set have a first angle relative to the surface of the micromirror device.

6. The system of claim 1 , further comprising:
a second camera, wherein the second camera comprises a plurality of light-sensitive elements disposed on a focal surface of the second camera;
a micromirror device, wherein the micromirror device comprises a substantially planar array of actuatable mirrors disposed on a surface, wherein respective angles of the actuatable mirrors relative to the surface are electronically controllable,
wherein the optical system optically couples the light source to the target via reflection from a first set of one or more of the actuatable mirrors, wherein the optical system optically couples the target to the second camera via reflection from the first set of one or more actuatable mirrors, and wherein the optical system optically couples the target to the spatial light modulator via reflection from a second set of one or more of the actuatable mirrors, and
wherein the one or more actuatable mirrors in the first set have a first angle relative to the surface of the micromirror device and the one or more actuatable mirrors in the second set have a second angle relative to the surface of the micromirror device that is different from the first angle.

7. The system of claim 1 , further comprising an actuated stage, wherein the actuated stage controls the location of the target relative to the optical system.

8. The system of claim 1 , wherein the spatial light modulator comprises an array of cells having respective electronically controllable refractive indexes.

9. A method comprising:
illuminating a target by a light source;
electronically controlling a spatial light modulator during a first period of time such that a refractive layer of the spatial light modulator has a refractive index that varies spatially across the spatial light modulator, wherein the spatial light modulator further comprises a reflective layer disposed beneath the refractive layer;
receiving, at the spatial modulator, light emitted from the target in response to the light from the light source;
reflecting, by the spatial modulator, the light received from the target to a first camera;
imaging, by the first camera, the light reflected by the spatial modulator during the first period of time to produce a first image of the target; and
determining spectrographic information for a particular region of the target based at least on the first image of the target.

10. The method of claim 9 , further comprising:
electronically controlling the spatial light modulator during a plurality of further periods of time such that the refractive index of the refractive layer varies spatially across the spatial light modulator; and
imaging light emitted from the target in response to the light from the light source during the plurality of further periods of time using the first camera to produce respective further images of the target, wherein determining spectrographic information for a particular region of the target comprises determining spectrographic information based on the first image and the plurality of further images of the target.

11. The method of claim 9 , further comprising:
controlling a spectral resolution of the spectrographic information for the particular region of the target by controlling the spatial variation of the refractive index of the refractive layer across the spatial light modulator.

12. The method of claim 11 , wherein the target contains a fluorophore, wherein a property of an emission spectrum of the fluorophore is related to a property of the target, wherein controlling a spectral resolution of the spectrographic information comprises controlling the spectrographic resolution to be sufficiently high to determine the property of the target based on determined spectrographic information for the particular region of the target.

13. The method of claim 11 , wherein the target contains two fluorophores, wherein the two fluorophores have respective different emission spectra, wherein controlling a spectral resolution of the spectrographic information comprises controlling the spectrographic resolution to be sufficiently high to determine whether the particular region of the target contains the first fluorophore or the second fluorophore based on determined spectrographic information for the particular region of the target.

14. The method of claim 9 , wherein the target contains a fluorophore, and wherein illuminating the target comprises emitting light at an excitation wavelength of the fluorophore.

15. The method of claim 9 , further comprising:
operating a micromirror device to electronically control respective angles of actuatable mirrors of the micromirror device relative to a surface during the first period of time, wherein the actuatable mirrors comprise a substantially planar array and are disposed on the surface, and wherein operating the micromirror device to electronically control respective angles of actuatable mirrors of the micromirror device comprises controlling a first set of one or more of the actuatable mirrors to have a first angle relative to the surface of the micromirror device during a specified period of time during the first period of time, and
wherein the target is illuminated by the light source via reflection from the first set of one or more actuatable mirrors, and wherein the spatial modulator receives the light emitted from the target in response to the light from the light source via reflection from the first set of one or more actuatable mirrors.

16. The method of claim 15 , wherein operating

Assignees

• Verily Life Sciences Llc

Inventors

• Acosta Victor Marcel
• Backer Adam
• Perreault John D
• Piponi Daniele Paolo

Classifications

• G06T7/90

  Determination of colour characteristics · 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

• G01J2003/468

  of objects containing fluorescent agent · CPC title

• G06T7/11

  Region-based segmentation · CPC title

• G02F1/133553

  Reflecting elements (associated to illuminating devices G02F1/133605) · CPC title