19 patents
Utility
Multispectral sample imaging
5 Dec 23
The disclosure features methods that include exposing a biological sample to illumination light and measuring light emission from the sample to obtain N sample images, where each sample image corresponds to a different combination of a wavelength band of the illumination light and one or more wavelength bands of the light emission, where the one or more wavelength bands of the light emission define a wavelength range, and where N>1, and exposing the sample to illumination light in a background excitation band and measuring light emission from the sample in a background spectral band to obtain a background image of the sample, where the background spectral band corresponds to a wavelength within the wavelength range.
Peter J. Miller, Kent S. Johnson, Carla Coltharp
Filed: 14 Apr 22
Utility
RNA Detection by Selective Labeling and Amplification
27 Apr 23
Methods for labeling biological samples include (a) contacting a biological sample featuring a target RNA with a probe, where the probe includes a capture moiety that specifically binds to the target RNA, and a plurality of reporter moieties, and (b) for each reporter moiety of the plurality of reporter moieties: contacting the reporter moiety with a catalytic agent that includes an oligonucleotide that specifically binds to the reporter moiety, and a reactive species linked to the oligonucleotide, and contacting the biological sample with a labeling agent that reacts with the reactive species to deposit the labeling agent or a derivative thereof in the sample in proximity to the target RNA.
Peter J. Miller, Julia Kennedy-Darling
Filed: 3 Aug 22
Utility
RNA Detection
23 Feb 23
Methods for RNA detection in biological samples include (a) contacting a biological sample with a first composition featuring multiple different types of unlabeled oligonucleotide probes that hybridize to RNA species in the sample; (b) contacting the biological sample with a hybridization agent featuring a chaotropic compound; (c) contacting the biological sample with a second composition that includes multiple different types of labeled oligonucleotide probes, where each of the different types of labeled oligonucleotide probes selectively hybridizes to one of the different types of unlabeled oligonucleotide probes; (d) obtaining at least one image of the biological sample with the multiple different types of labeled oligonucleotide probes bound to the sample; and (e) identifying spatial locations of the RNA species in the sample based on components of the at least one image that correspond to the different types of labeled oligonucleotide probes, where the biological sample is contacted with the second composition under isothermal conditions.
Julia Kennedy-Darling, Peter J. Miller
Filed: 21 Dec 20
Utility
Amplification of RNA Detection Signals in Biological Samples
17 Nov 22
Methods include contacting a biological sample with a first probe, where the first probe includes a capture moiety having an oligonucleotide sequence that selectively binds to a RNA in the sample, and a secondary oligonucleotide region that does not bind to the RNA, contacting the sample with a second probe, where the second probe includes a probe binding region that is complementary to, and hybridizes to, a portion of the secondary oligonucleotide region, and includes a reporter moiety, and extending the secondary oligonucleotide region using the second probe as a template to generate an extended secondary oligonucleotide region featuring multiple copies of the reporter moiety, where the reporter moiety includes a plurality of label regions each featuring an oligonucleotide sequence, and one or more of the label regions of the reporter moiety are different from the other label regions of the reporter moiety.
Garry Nolan, Julia Kennedy-Darling, Peter J. Miller
Filed: 13 May 22
Utility
Detection of co-occurring receptor-coding nucleic acid segments
11 Oct 22
Methods for identifying co-occurrence of nucleic acid segments in a nucleic acid sample from a specimen including obtaining a nucleic acid sample from a specimen, determining sequences of first and second nucleic acid segments in nucleic acid fragments of the sample to generate a first and second sets of sequences, generating a first and second sets of probes from the first and second sets of sequences, exposing a detection sample to a member of the first set of probes and a member of the second set of probes, performing a hybridization analysis to determine whether the members of the first and second sets of probes hybridize to the detection sample, and determining whether the first and second nucleic acid segments co-occur in a common cell of the specimen.
Steven Daniel
Filed: 21 Oct 19
Utility
Detection of Labeled Analytes In Biological Samples
6 Oct 22
Methods for determining locations of analytes include: (a) exposing a biological sample to a plurality of different types of probes, where each different type of probe includes a nucleic acid capture moiety and a detection moiety that includes at least one reporter moiety, where the at least one reporter moiety features multiple label regions, each of the label regions including an oligonucleotide having a sequence; (b) exposing the biological sample to a plurality of optical labels; (c) measuring optical signals generated by optical labels; (d) repeating steps (b) and (c) with different pluralities of optical labels; (e) identifying one or more of the reporter moieties in the sample based on the measured optical signals; and (f) determining a location of one or more of the RNA analytes in the sample based on the identified reporter moieties.
Peter J. Miller, Julia Kennedy-Darling
Filed: 6 Apr 22
Utility
Surface sensing in optical microscopy and automated sample scanning systems
27 Sep 22
The disclosure features methods and systems that include positioning a surface of a coverslip overlying a sample relative to an object plane of a microscope system, projecting a two-dimensional pattern of light onto the surface, where a focal plane of the two-dimensional pattern at a position of the surface is rotated by an angle β relative to the object plane, obtaining a two-dimensional image of the pattern of light reflected from the surface using a detector that includes an imaging sensor oriented perpendicular to a direction of propagation of the reflected pattern of light at the sensor, analyzing the image to determine a line of best focus of the pattern within the image, determining an offset of the line of best focus from an expected position of the line of best focus within the image, and determining a position adjustment of the surface based on the offset.
Russell Gershman, Peter J. Miller, Olavi Ollikainen
Filed: 11 Dec 17
Utility
Multispectral Sample Imaging
4 Aug 22
The disclosure features methods that include exposing a biological sample to illumination light and measuring light emission from the sample to obtain N sample images, where each sample image corresponds to a different combination of a wavelength band of the illumination light and one or more wavelength bands of the light emission, where the one or more wavelength bands of the light emission define a wavelength range, and where N>1, and exposing the sample to illumination light in a background excitation band and measuring light emission from the sample in a background spectral band to obtain a background image of the sample, where the background spectral band corresponds to a wavelength within the wavelength range.
Peter J. Miller, Kent S. Johnson, Carla Coltharp
Filed: 14 Apr 22
Utility
Analyte Detection by Selective Labeling of Biological Samples
28 Apr 22
The disclosure features methods that include: contacting a biological sample having a first target analyte with a first agent, where the first agent includes a first binding species that specifically binds to the first target analyte, and a first oligonucleotide conjugated to the binding species; contacting the biological sample with a second agent, where the second agent includes a first reactive species and a second oligonucleotide conjugated to the first reactive species, to hybridize at least a portion of the second oligonucleotide to at least a portion of the first oligonucleotide; and contacting the biological sample with a first labeling species, where the first labeling species reacts with the first reactive species to deposit the first labeling species or a derivative thereof in the biological sample.
Peter J. Miller, Julia Kennedy-Darling, Yi Zheng, Clifford C. Hoyt, Gajalakshmi Dakshinamoorthy
Filed: 4 Feb 20
Utility
Multispectral sample imaging
19 Apr 22
The disclosure features methods that include exposing a biological sample to illumination light and measuring light emission from the sample to obtain N sample images, where each sample image corresponds to a different combination of a wavelength band of the illumination light and one or more wavelength bands of the light emission, where the one or more wavelength bands of the light emission define a wavelength range, and where N>1, and exposing the sample to illumination light in a background excitation band and measuring light emission from the sample in a background spectral band to obtain a background image of the sample, where the background spectral band corresponds to a wavelength within the wavelength range.
Peter J. Miller, Kent S. Johnson, Carla Coltharp
Filed: 3 May 19
Utility
Multiplexed Imaging Reagent Compositions and Kits
3 Mar 22
Methods for detecting multiple target analytes in a biological sample include: (a) contacting the biological sample with a plurality of different types of probes, where each different type of probe includes a capture moiety that selectively binds to a different target analyte in the sample, and an oligonucleotide having a sequence that is unique among other types of probes in the plurality of different types of probes; (b) binding an optical label to one of the different types of probes; (c) contacting the sample with a composition that includes at least one blocking agent, where the at least one blocking agent includes an oligonucleotide having a sequence that hybridizes to the oligonucleotide of another type of probe from among the different types of probes; and (d) obtaining an image of the sample that includes information corresponding to one or more locations of the one type of probe in the sample.
Peter J. Miller
Filed: 26 Aug 21
Utility
Processing and Imaging Tissue Samples
20 Jan 22
Methods include applying a first stain composition comprising a fluorescent counterstain to a biological sample, measuring information corresponding to one or more stains of the first stain composition, removing the fluorescent counterstain from the biological sample, applying a second stain composition to the biological sample, measuring information corresponding to one or more stains of the second stain composition in the biological sample, where the one or more stains include a fluorescent label, and generating a first image of the biological sample, where the first image corresponds to a pattern of simulated hematoxylin staining in the biological sample.
Michael McLane
Filed: 20 Jul 21
Utility
Multiplexed Imaging with Enzyme Mediated Amplification
22 Jul 21
Methods for imaging an analyte in a sample include contacting the biological sample with a binding agent, where the binding agent includes a binding moiety that binds to the analyte and a first nucleotide sequence, contacting the biological sample with a catalytic agent, where the catalytic agent includes a second nucleotide sequence linked to an enzyme, and where the second nucleotide sequence hybridizes to the first nucleotide sequence, contacting the biological sample with a localization agent, where the localization agent includes a substrate complementary to the enzyme and a third nucleotide sequence linked to the substrate, and contacting the biological sample with a labeling agent, where the labeling agent includes a fourth nucleotide sequence linked to an optical label, where the fourth nucleotide sequence hybridizes to the third nucleotide sequence.
Grady Carlson
Filed: 30 Sep 20
Utility
Flexible Detection Systems
20 May 21
Provided herein are methods, kits, and compositions for the detection of an element of a biological sample using an antibody conjugated to a first oligonucleotide, which connects to a labelled oligonucleotide for detection via an oligonucleotide partially complementary to the first oligonucleotide and partially complementary to the second oligonucleotide.
Julia Kennedy-Darling, Joseph Kim, Gajalakshmi Dakshinamoorthy, Brian McKelligon
Filed: 28 Jan 21
Utility
Multispectral imaging systems and methods
30 Mar 21
The methods and systems disclosed herein include obtaining a first image of a sample, where the first image corresponds to light transmitted through the sample in a first plurality of distinct spectral bands, obtaining a second image of the sample, where the second image corresponds to light transmitted through the sample in a second plurality of distinct spectral bands, and where at least some members of the second plurality of spectral bands are different from the members of the first plurality of spectral bands, and combining the first and second images to form a multispectral image stack, where each pixel in the image stack includes information corresponding to at least four distinct spectral bands, and where the at least four distinct spectral bands include at least one member from the first plurality of spectral bands and at least one member from the second plurality of spectral bands.
Peter J. Miller
Filed: 7 Jan 14
Utility
Multiplexed Tissue Imaging
16 Dec 20
An apparatus attaches to a microscope slide to form an enclosed fluidic chamber with input and output ports, where a tissue or cell sample on the slide can be processed using techniques such as immunohistochemical staining.
Julia Kennedy-Darling, Peter J. Miller, Peter Harvey, Gajalakshmi Dakshinamoorthy
Filed: 14 Jun 20
Utility
Detection of Co-Occurring Receptor-Coding Nucleic Acid Segments
22 Apr 20
Methods for identifying co-occurrence of nucleic acid segments in a nucleic acid sample from a specimen including obtaining a nucleic acid sample from a specimen, determining sequences of first and second nucleic acid segments in nucleic acid fragments of the sample to generate a first and second sets of sequences, generating a first and second sets of probes from the first and second sets of sequences, exposing a detection sample to a member of the first set of probes and a member of the second set of probes, performing a hybridization analysis to determine whether the members of the first and second sets of probes hybridize to the detection sample, and determining whether the first and second nucleic acid segments co-occur in a common cell of the specimen.
Steven Daniel
Filed: 20 Oct 19
Utility
Whole slide multispectral imaging systems and methods
2 Mar 20
The methods and systems disclosed herein include obtaining a first plurality of images of a sample, where each image in the first plurality of images corresponds to a different spectral band of illumination light incident on the sample or emission light from the sample, obtaining a second plurality of images of the sample, where each image in the second plurality of images corresponds to a different spectral band of illumination light incident on the sample or emission light from the sample, aligning the first and second pluralities of images based on information from a first image from the first plurality of images and a second image from the second plurality of images, where the first and second images correspond to a shared spectral band, and combining at least some members of the first plurality of images and at least some members of the second plurality of images to form an image stack.
Peter J. Miller
Filed: 6 Jan 14
Utility
Multispectral Sample Imaging
6 Nov 19
The disclosure features methods that include exposing a biological sample to illumination light and measuring light emission from the sample to obtain N sample images, where each sample image corresponds to a different combination of a wavelength band of the illumination light and one or more wavelength bands of the light emission, where the one or more wavelength bands of the light emission define a wavelength range, and where N>1, and exposing the sample to illumination light in a background excitation band and measuring light emission from the sample in a background spectral band to obtain a background image of the sample, where the background spectral band corresponds to a wavelength within the wavelength range.
Peter J. Miller, Kent S. Johnson, Carla Coltharp
Filed: 2 May 19
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