Digitally enhanced microscopy for multiplexed histology
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Publication Number
US-12587724-B2
Publication Date
2026-03-24
Expiration Date
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.
Core Innovation
The invention relates to an imaging system for imaging a sample on a microscope slide. The system includes an energy emitter with 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 image capture devices. The controller captures a first monochrome image exposed to a first light waveband that interacts with a first target, and a second monochrome image exposed to a second light waveband different from the first light waveband and interacting with a second target.
The controller assigns a first false color for the first target and a second false color for the second target, where the second false color is different from the first false color. The controller combines 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 outputs the enhanced composite image.
In additional embodiments, the system determines the first and second light wavebands and performs sequential illumination of the sample with the first light waveband and the second light waveband. Further embodiments select at least one false color protocol representing a multi-feature staining protocol, assign false colors for multiple features according to the protocol, combine the false-colored features to generate a labelled false color image, and output an enhanced composite image.
Claims Coverage
The consolidated content provides four inventive features. Across the independent claims, the inventive features center on multiplexed monochrome imaging with different light wavebands, false-color assignment, enhanced composite generation, trained-classifier feature identification, and protocol-driven multi-feature labeling.
Two monochrome images with different light wavebands and false-color assignment
Capturing a first monochrome image exposed to a first light waveband that interacts with a first target, capturing a second monochrome image exposed to a second light waveband that interacts with a second target and differs from the first light waveband, assigning a first false color for the first target and a second false color for the second target, combining the first target and 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.
Trained classifier feature identification in enhanced composite
Combining the first target illustrated in a first false color and the second target illustrated in a second false color different from the first false color to generate the enhanced composite image of the sample, and identifying one or more features of interest in the enhanced composite image using a trained classifier.
Sequential illumination with determined light wavebands for enhanced false-color image
Determining a first light waveband for interacting with a first target and a second light waveband for interacting with a second target, performing an illumination protocol to sequentially illuminate the sample with the first light waveband and the second light waveband, capturing a first monochrome image while illuminated with the first light waveband and a second monochrome image while illuminated with the second light waveband, and generating an enhanced image in which the first target is illustrated in a first false color and the second target is illustrated in a second false color different from the first false color.
Multi-feature staining protocol false-color labeling and enhanced composite output
Selecting at least one false color protocol representing a multi-feature staining protocol for visually identifying multiple features of the sample, assigning a first false color for the first feature according to the at least one false color protocol and assigning a second false color for the second feature according to the at least one false color protocol with the second false color different from the first false color, combining the first feature and the second feature illustrated in the first and second false colors to generate a labelled false color image of the sample including the first false color first feature and the second false color second feature, and outputting an enhanced composite image.
The independent claims cover an imaging workflow that captures monochrome images under different light wavebands, maps different sample targets or features to distinct false colors according to single or protocol-based mappings, combines the false-colored components into an enhanced composite image, and optionally identifies features of interest using a trained classifier.
Stated Advantages
Enables generation of an enhanced composite image by combining targets illustrated in different false colors based on different light wavebands.
Allows visually distinct representation of multiple targets/features using false colors assigned to respective targets/features.
Enables identifying one or more features of interest in the enhanced composite image using a trained classifier.
Documented Applications
Multiplex assays including HER2/Chromosome 17 in situ hybridization (ISH) with chromogenic detection, including use cases associated with slide staining kits such as ULTRAVIEW SISH Detection Kit and INFORM HER2 Dual ISH DNA Probe [procedural detail omitted for safety].
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