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US 2026/0287575 A1Published application
Label-free methods for assessing cell state in a biological sample
AssigneeElephas Biosciences Corporation
InventorsJason Smith, Chao Liu, Jonathan Ouellette, Jonathan Daniel Oliner, Eric Wait, John Daniel Rafter
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Abstract
Provided herein are methods of assessing cell state within a biological sample. In particular, the present invention provides techniques for identifying a live cell fraction within a biological sample through use of OCM/dOCM imaging, and determining a metabolic signature of the identified live cell fraction through use of FLIM imaging. The present invention further provides techniques for assessing changes in cell state of a live cell fraction within a biological sample through use of OCM/dOCM and FLIM imaging in response to a pharmaceutical intervention.
Claims122
A method of evaluating a biological sample, comprising
- a) imaging the biological sample with OCM/dOCM (e.g., OCM and/or dOCM) to identify a live cell fraction in the biological sample;
- and
- b) imaging the biological sample with FLIM to classify the cell state within the identified live cell fraction.
An ex vivo method of assessing one or more potential therapeutic agents, comprising
- a) imaging a biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- b) imaging the biological sample with FLIM to classify the cell state within the biological;
- c) contacting the biological sample with one or more potential therapeutic agents, wherein the contacting is subsequent to the imaging of the biological sample with OCM/dOCM and FLIM;
- and
- d) imaging the biological sample with OCM/dOCM and/or FLIM to re-classify the cell state within the biological sample to measure classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents.
2 more elements
An ex vivo method of assessing a biological sample, comprising:
- providing
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM and/or dOCM to identify a live cell fraction in the biological sample;
- and
- image the biological sample with FLIM to classify the cell state within the identified live cell fraction;
- and
- provide a report to a user of the identified and classified live cell fraction;
- executing the processor to
- image the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- and
- image the biological sample with FLIM to classify the cell state within the identified live cell fraction, and
- provide a report to a user of the identified and classified live cell fraction.
10 more elements
An ex vivo method of assessing one or more potential therapeutic agents, comprising providing:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- image the biological sample with FLIM to classify the cell state within the biological sample;
- contact the biological sample with one or more potential therapeutic agents subsequent to the imaging of the biological sample with OCM/dOCM and FLIM;
- image the biological sample with OCM/dOCM and/or FLIM to re-classify the cell state within the biological sample;
- measure classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- and
- classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents;
- executing the software to:
- image the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- image the biological sample with FLIM to classify the cell state within the biological sample;
- contact the biological sample with one or more potential therapeutic agents subsequent to the imaging of the biological sample with OCM/dOCM and FLIM;
- image the biological sample with OCM/dOCM and/or FLIM to re-classify the cell state within the biological sample;
- measure classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- and
- classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents.
20 more elements
A system comprising:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM/dOCM (e.g., OCM and/or dOCM) to identify a live cell fraction in the biological sample;
- and
- image the biological sample with FLIM to classify the cell state within the biological sample;
- and
- provide a report to a user of the identified and classified live cell fraction and/or biological sample.
4 more elements
A system comprising:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM/dOCM (e.g., OCM and/or dOCM) to identify a live cell fraction in the biological sample;
- image the biological sample with FLIM to classify the cell state within the biological sample;
- contact the biological sample with one or more potential therapeutic agents subsequent to the imaging of the biological sample with OCM/dOCM and FLIM;
- image the biological sample with OCM/dOCM and/or FLIM to re-classify the cell state within the biological sample;
- measure classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- classification differences pre- and post-contacting of the biological sample with the one or more potential therapeutic agents;
- and
- classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents.
10 more elements
A method of evaluating a biological sample, the method comprising:
- a) imaging a biological sample with optical coherence microscopy (OCM) and/or dynamic optical coherence microscopy (dOCM), thereby identifying a live cell fraction in the biological sample;
- and
- b) imaging the biological sample with fluorescence lifetime imaging microscopy (FLIM) to classify cell state within the live cell fraction of the biological sample.
A method of evaluating a biological sample, the method comprising:
- a) imaging a biological sample with optical coherence microscopy (OCM) and/or dynamic optical coherence microscopy (dOCM), thereby identifying a live cell fraction of the biological sample;
- and
- b) imaging the biological sample with fluorescence lifetime imaging microscopy (FLIM) to determine a baseline metabolic signature for the live cell fraction of the biological sample.
A method of evaluating a potential therapeutic agent, the method comprising:
- a) imaging a biological sample with optical coherence microscopy (OCM) and/or dynamic optical coherence microscopy (dOCM), thereby identifying a live cell fraction of a biological sample;
- b) contacting the biological sample with a potential therapeutic agent;
- c) measuring a metabolic shift in the live cell fraction from a baseline metabolic signature for the live cell fraction;
- and
- d) classifying cell state within the live cell fraction based upon the metabolic shift measured in the live cell fraction.
2 more elements
A method of evaluating a biological sample, the method comprising:
- a) contacting a biological sample with a potential therapeutic agent, wherein the potential therapeutic agent comprises a leukocyte;
- and
- b) imaging the biological sample with fluorescence lifetime imaging microscopy (FLIM) to classify cell state in the biological sample.
A method of evaluating a potential therapeutic agent, the method comprising:
- a) contacting a biological sample with a potential therapeutic agent, wherein the potential therapeutic agent comprises a leukocyte,
- b) measuring a metabolic shift in the biological sample from a baseline metabolic signature for the biological sample;
- and
- c) classifying cell state within the biological sample based upon the metabolic shift measured.
1 more element
A method of evaluating a biological sample, comprising
- a) imaging the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- and
- b) imaging the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction.
An ex vivo method of assessing one or more potential therapeutic agents, comprising
- a) imaging a biological sample with OCM and/or dOCM to identify a live cell fraction in the biological sample;
- b) imaging the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- c) contacting the identified and classified live cell fraction with one or more potential therapeutic agents;
- and
- d) imaging the identified live cell fraction with OCM/dOCM and/or FLIM to re-classify the cell state within the identified live cell fraction to measure classification differences pre- and post-contacting of the identified and classified live cell fraction with the one or more potential therapeutic agents.
2 more elements
An ex vivo method of assessing a biological sample, comprising:
- providing
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM and/or dOCM to identify a live cell fraction in the biological sample;
- and
- image the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- and
- provide a report to a user of the identified and classified live cell fraction;
- executing the processor to
- image the biological sample with OCM and/or dOCM to identify a live cell fraction in the biological sample;
- and
- image the identified live cell fraction with OCM/dOCM and/or FLIM to classify the cell state within the identified live cell fraction, and
- provide a report to a user of the identified and classified live cell fraction.
10 more elements
An ex vivo method of assessing one or more potential therapeutic agents, comprising providing:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM and/or dOCM to identify a live cell fraction in the biological sample;
- image the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- contact an identified and classified live cell fraction with one or more potential therapeutic agents after an identification and classification of a live cell fraction with OCM and/or dOCM and FLIM;
- image the identified and classified live cell fraction with FLIM to re-classify the cell state within the identified and classified live cell fraction;
- measure classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- and
- classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents;
- executing the software to:
- image the biological sample with optical coherence microscopy (OCM) and/or dynamic optical coherence microscopy (dOCM) to identify a live cell fraction in the biological sample;
- image the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- contact an identified and classified live cell fraction with one or more potential therapeutic agents after an identification and classification of a live cell fraction with OCM and/or dOCM and FLIM;
- image the identified and classified live cell fraction with fluorescence lifetime imaging microscopy (FLIM) to re-classify the cell state within the identified and classified live cell fraction;
- measure classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- and
- classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents.
20 more elements
A system comprising:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- and
- image the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- and
- provide a report to a user of the identified and classified live cell fraction.
4 more elements
A system comprising:
- a biological sample, and
- a processor comprising software that, when executed, causes the processor to manually or automatically:
- image the biological sample with OCM/dOCM to identify a live cell fraction in the biological sample;
- image the identified live cell fraction with FLIM to classify the cell state within the identified live cell fraction;
- contact an identified and classified live cell fraction with one or more potential therapeutic agents after an identification and classification of a live cell fraction with OCM and/or dOCM and FLIM;
- re-image the identified and classified live cell fraction with OCM/dOCM and/or FLIM to re-classify the cell state within the identified and classified live cell fraction;
- measure classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents;
- provide a report to a user of one or more of:
- an identified and classified live cell fraction;
- a re-classified identified and classified live cell fraction;
- and
- classification differences pre- and post-contacting of identified and classified live cell fraction with the one or more potential therapeutic agents.
9 more elements
Dependencies are inferred from the claim text.