Digitally enhanced microscopy for multiplexed histology

Patent metadata

Field	Value
Publication number	US-12587724-B2
Application number	US-202418886939-A
Country	US
Kind code	B2
Filing date	Sep 16, 2024
Priority date	Mar 12, 2013
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

Disclosed herein are embodiments of imaging biological specimens. An imaging system can include a microscope for directly viewing the biological specimen and a multi-spectral imaging apparatus for outputting digitally enhanced images, near-video rate imaging, and/or videos of the specimen. An imaging system can include a digital scanner that digitally processes images to produce a composite image with enhanced color contrast of features of interest.

First claim

What is claimed is:

1 . An imaging system for imaging a sample on a microscope slide, the imaging system comprising:
an energy emitter including a first light source and a second light source; one or more image capture devices; and a controller communicatively coupled to the energy emitter and the one or more image capture devices, the controller including at least one processor and memory storing instructions that, when executed by the at least one processor, cause the imaging system to perform a process including:
capturing, using the one or more image capture devices,
a first monochrome image of the sample exposed to a first light waveband from the first light source, wherein the first light waveband interacts with a first target of the sample, and
a second monochrome image of the sample exposed to a second light waveband from the second light source, wherein the second light waveband interacts with a second target of the sample, wherein the second light waveband is different from the first light waveband,

assigning a first false color for the first target,
assigning a second false color for the second target, wherein the second false color is different from the first false color,
combining the first target and the second target illustrated in the first and second false colors to generate an enhanced composite image of the sample, and
outputting the enhanced composite image.

2 . The imaging system of claim 1 , wherein the first light waveband is an ultraviolet waveband, a near infrared waveband, or an infrared waveband.

3 . The imaging system of claim 1 , wherein at least one of the first light source or the second light source includes an ultraviolet light source, a near infrared light source, or an infrared light source.

4 . The imaging system of claim 1 , wherein the enhanced composite image of the sample is an enhanced color composite image having an enhanced color contrast between the first and second targets greater than a natural color contrast between the first and second targets.

5 . The imaging system of claim 1 , wherein the process further comprises:
obtaining a detection protocol for the sample; analyzing the enhanced composite image according to the detection protocol to
identify one or more features of interest of the sample; and
labelling at least one of the features of interest in the enhanced composite image.

6 . The imaging system of claim 1 , wherein the process further comprises:
obtaining stain information for the sample; and determining the first false color for the first target based on the stain information.

7 . The imaging system of claim 1 , wherein the process further comprises:
obtaining stain information for multiple stains applied to the sample; and determining the first false color for the first target based on the stain information and characteristics of the second target in the second monochrome image.

8 . The imaging system of claim 1 , wherein outputting the enhanced composite image includes transmitting the enhanced composite image to a trained classifier configured to identify one or more features of interest in the enhanced composite image, and wherein the trained classifier has been trained using a set of training slides and one or more detection algorithms.

9 . The imaging system of claim 1 , wherein the process further comprises:
pulsing the first and second light sources, and synchronizing capturing of the first and second monochrome images with pulsing of the first and second light sources.

10 . The imaging system of claim 9 , wherein each of the first and second light sources includes a light-emitting diode.

11 . The imaging system of claim 1 , wherein the one or more image capture devices include a digital camera.

12 . The imaging system of claim 1 , wherein:
in the first monochrome image, the sample is exposed only to the first light waveband from the first light source; and in the second monochrome image, the sample is exposed only to the second light waveband from the second light source.

13 . An imaging system for imaging a sample on a microscope slide, comprising:
a slide imager configured to generate an enhanced composite image of the sample, the slide imager including:
an energy emitter including a first light source and a second light source;
one or more image capture devices; and
a controller communicatively coupled to the energy emitter and the one or more image capture devices, the controller including at least one processor and memory storing program instructions that, when executed by the at least one processor, cause the slide imager to perform a process including:
capturing, using the one or more image capture devices,
a first monochrome image of the sample exposed to a first light waveband from the first light source, wherein the first light waveband interacts with a first target of the sample, and
a second monochrome image of the sample exposed to a second light waveband from the second light source, wherein the second light waveband interacts with a second target of the sample, wherein the second light waveband is different from the first light waveband,

combining the first target illustrated in a first false color and the second target illustrated in a second false color different than the first false color to generate the enhanced composite image of the sample, and
identifying, using a trained classifier, one or more features of interest in the enhanced composite image.

14 . The imaging system of claim 13 , wherein at least one of the first light source or the second light source includes an ultraviolet light source, a near infrared light source, or an infrared light source.

15 . The imaging system of claim 13 , wherein the trained classifier has been trained using a set of training slides and one or more detection algorithms.

16 . The imaging system of claim 13 , further comprising a slide handler mechanism configured to deliver the microscope slide to the slide imager and to remove the microscope slide from the slide imager.

17 . The imaging system of claim 16 , wherein the slide handler mechanism includes at least one of a robotic arm, a XYZ slide handler, a gripping mechanism, or a transport device.

18 . The imaging system of claim 13 , further comprising an automated slide staining instrument configured to stain the sample, and wherein the controller is programmed to select the first or second false color based on at least one stain that has been applied to the sample by the automated slide staining instrument.

19 . The imaging system of claim 13 , wherein the first light waveband has a full width at half maximum between about 30 nm and about 250 nm.

20 . An imaging system for imaging a sample on a microscope slide, the imaging system comprising:
an energy emitter including a light source; one or more image capture devices; and a controller communicatively coupled to the energy emitter and the one or more image capture devices, the controller including at least one processor and memory storing instructions that, when executed by the at least one processor, cause the imaging system to perform a process including:
determining, using the at least one processor, a first light waveband for interacting with a first target of the sample and a second light waveband for interacting with a second target of the sample,
performing an illumination protocol via the light source to sequentially illuminate the sample with the first light waveband and the second light

Assignees

• Ventana Med Syst Inc

Inventors

• Morrison Larry
• Dietz Lou

Classifications

• G01N21/6458 Primary

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

• H04N23/11 Primary

  for generating image signals from visible and infrared light wavelengths · CPC title