Device for detection of cellular stress

Patent metadata

Field	Value
Publication number	US-12055536-B2
Application number	US-202318317637-A
Country	US
Kind code	B2
Filing date	May 15, 2023
Priority date	Jun 14, 2021
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

Disclosed is an assay for determining resistance in a target cell or tissue to a therapy associated with cellular stress using chemical microscopy and high-throughput single cell analysis to determine functional metabolic alteration, including determining metabolic reprogramming in a target cell or tissue to a therapy associated with cellular stress, and methods of using the assays.

First claim

We claim:

1. An assay for determining resistance in a target cell to a therapy, the assay comprising:
measuring glucose and glycolysis derived anabolism in the target cell;
measuring fatty acid uptake and oxidation in the target cell; and
determining a change from glucose anabolism in the target cell to fatty acid uptake and oxidation energy metabolism.

2. The assay of claim 1 , wherein chemical microscopy is used to measure glucose and glycolysis derived anabolism and fatty acid uptake and oxidation.

3. The assay of claim 2 , wherein the chemical microscopy is Raman scattering microscopy or infrared microscopy.

4. The assay of claim 3 , wherein the Raman scattering microscopy is selected from the group consisting of: spontaneous Raman scattering microscopy, surface enhanced Raman scattering microscopy, coherent anti-stokes Raman scattering (CARS), stimulated Raman scattering (SRS) microscopy, and hyperspectral stimulated Raman scattering imaging.

5. The assay of claim 3 , wherein the infrared microscopy is selected from the group consisting of: mid-infrared photothermal (MIP) microscopy, direct infrared absorption based microscopy, fourier-transformed infrared (FTIR) microscopy, and quantum cascade laser (QCL) microscopy.

6. The assay of claim 1 , further comprising measuring de novo lipogenesis in the target cell and determining a change from glucose and glycolysis dependent anabolism and de novo lipogenesis in the target cell to fatty acid uptake and oxidation energy metabolism.

7. The assay of claim 1 , wherein the therapy induces cellular stress in the target cell.

8. The assay of claim 7 , wherein the cellular stress is oxidative stress, metabolic stress, hypoxic stress, nutrient stress, thermal stress, genotoxic stress, or combinations thereof.

9. The assay of claim 1 , wherein the therapy is a cancer therapy.

10. The assay of claim 9 , wherein the cancer therapy is selected from chemotherapy, radiotherapy, immunotherapy, targeted therapy, hormone therapy, light therapy, laser therapy, photodynamic therapy, and combinations thereof.

11. The assay of claim 9 , wherein the cancer therapy is chemotherapy comprising one or more platinum-based agents, nitrosoureas, anti-metabolites, anti-tumor antibiotics, plant alkaloids, topoisomerase inhibitors, mitotic inhibitors, hormonal agents, corticosteroids, biological response modifiers, carboplatin, and/or oxaliplatin.

12. The assay of claim 9 , wherein the cancer therapy is configured to treat one or more of ovarian, prostate, testicular, bladder, head, neck, pancreatic, lung, breast, and esophageal cancer.

13. A method of treating a subject to inhibit resistance to a cancer therapy, the method comprising:
obtaining a cancer cell from the subject;
performing the assay of claim 1 on the cancer cell; and
administering the cancer therapy to the subject.

14. The method of claim 13 , wherein the cancer therapy is selected from chemotherapy, radiotherapy, immunotherapy, targeted therapy, hormone therapy, light therapy, laser therapy, photodynamic therapy, and combinations thereof.

15. The method of claim 14 , wherein the cancer therapy is chemotherapy comprising one or more platinum-based agents, nitrosoureas, anti-metabolites, anti-tumor antibiotics, plant alkaloids, topoisomerase inhibitors, mitotic inhibitors, hormonal agents, corticosteroids, biological response modifiers, carboplatin, and/or oxaliplatin.

16. The method of claim 13 , wherein the cancer cell is selected from ovarian, prostate, testicular, bladder, pancreatic, lung, breast, esophageal, head, and neck cancer.

17. The method of claim 13 , further comprising administering at least one inhibitor of fatty acid oxidation to the subject.

18. The method of claim 17 , wherein the at least one inhibitor of fatty acid oxidation is selected from etomoxir, oxfenicine, perhexiline, mildronate, trimetazidine, and combinations thereof.

19. The method of claim 13 , wherein the subject is a mammal.

20. The method of claim 19 , wherein the subject is a human.

Assignees

• Univ Boston
• Univ Northwestern

Inventors

• Cheng Ji-Xin
• Li Junjie
• Tan Yuying
• Matei Daniela
• Zhao Guangyuan

Classifications

• G01Q60/60

  SECM [Scanning Electro-Chemical Microscopy] or apparatus therefor, e.g. SECM probes · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/48735

  Investigating suspensions of cells, e.g. measuring microbe concentration (by chemical means C12Q1/04; colony counters C12M1/34; concentration of particle suspensions in general G01N15/06) · CPC title

• G01N27/416

  Systems (G01N27/27 takes precedence) · CPC title

• G01N27/30

  Electrodes, e.g. test electrodes; Half-cells (G01N27/414 takes precedence) · CPC title