Vibrational probes for metabolic imaging in live cells and organisms

This technology is a method for using small vibrational chemical tags combined with functional bioorthogonal infrared imaging to provide high-speed, high-sensitivity imaging of metabolic processes in live cells, tissues, and organisms which may be useful for disease diagnoses and assessments.

Unmet Need: Non-destructive, high temporal and spatial resolution imaging of biological samples

Current techniques used to visualize metabolic functions are limited by the lack of tools for accurately labeling and quantifying target molecules. Additionally, complementary techniques with high specificity often require destruction of the sample, cause perturbations of normal biological activities, or are associated with high cost and limited spatial and temporal resolution. There is a need for a high temporal and spatial resolution metabolic imaging technique that is not destructive to tissues and can be used on whole organisms in situ.

The Technology: High-resolution imaging using vibrational probes and high-speed infrared spectroscopy

This technology describes the incorporation of carbon deuterium into live cells, tissues or organisms to visualize cellular macromolecules and metabolic processes in real-time. Bioorthogonal infrared (IR) imaging of vital biometabolites can be further enhanced by coupling quantum cascade laser IR spectroscopy methods to speed up the imaging process and increase field of view. This technology enables subcellular-resolution imaging without destruction of live cells or tissues at high speeds. The high specificity of this technique also allows for whole-organism metabolic imaging that may be useful for cancer diagnosis, stroke assessment, perfusion deficits, drug screening, and other processes influenced by cellular metabolism.

Aspects of this technology has been validated in mouse models, demonstrating high-resolution and chemically informative assessment of glucose metabolism in various murine tissues including tumors, brain, intestine and liver. Tunable quantum cascade laser applications have been tested in vitro on living cell and tissue samples.

Applications:

• Research tool for metabolic imaging of biological processes
• Method for determining metabolic activity of skin
• Assessment and demarcation of cancer borders in various tissues
• Medical imaging of cellular tissue status and composition
• Assessment of blood flow and perfusion in surgery, trauma, cardiac arrest, etc.
• Screening and diagnosis for infection, cancer, endocrine disorders, etc.
• Imaging and monitoring of drug metabolism and efficacy
• Drug screening and toxicology assessment
• Compatible with whole brain or whole organ imaging
• Detection of metabolic heterogeneity of microbes or organisms for screening genes and detecting mutations
• Tumor detection, progression, and intratumor metabolic heterogeneity studies
• Indicator in studying other disease developments (e.g. Alzheimer’s, diabetes, obesity)

Advantages:

• Non-destructive to cells and tissues
• Non-invasive, requiring only small dosage of tags
• IR tags can be attached to different targeted molecules
• Background-free, highly sensitive imaging
• Subcellular spatial resolution in situ
• Compatible with other imaging modalities
• In vivo imaging of live cells, plants, microbes, animals, and humans
• High-speed image processing
• Ability to image larger fields of view
• Expansion of the scope of vibrational tags
• Larger cross section and increased speed and sensitivity compared to techniques such as stimulated Raman scattering

Lead Inventor:

Wei Min, Ph.D.

Patent Information:

Patent Issued (US 12,062,422)

Related Publications:

• Shou J, Oda R, Hu F, Karasaw K, Nuriya M, Yasui M, Shiramizu B, Min W, Ozeki Y. “Super-multiplex imaging of cellular dynamics and heterogeneity by integrated stimulated Raman and fluorescence microscopy” iScience. 2021 Jul 9; 24(8): 102832.

• Chen C, Zhao Z, Qian N, Wei S, Hu F, Min W. “Multiplexed live-cell profiling with Raman probes” Nat Commun. 2021 Jun 7; 12(1): 3405.

• Xiong H, Qian N, Miao Y, Zhao Z, Chen C, Min W. “Super-resolution vibrational microscopy by stimulated Raman excited fluorescence” Light Sci Appl. 2021 Apr 20; 10(1): 87.

• Shou J, Hu F, Oda R, Min W, Ozeki Y. “High-speed super-multiplex organelle imaging” SPIE BiOS. 2020 Feb 21; 11252: 112521C.

• Shi L, Hu F, Min W. “Optical mapping of biological water in single live cells by stimulated Raman excited fluorescence microscopy” Nat Commun. 2019 Oct 18; 18;10(1):4764.

• Hu F, Shi L, Min W. “Biological imaging of chemical bonds by stimulated Raman scattering microscopy” Nature Methods. 2019; 16, 830.

• Zhang L, Shi L, Shen Y, Miao Y, Wei M, Qian N, Liu Y, Min W. “Spectral tracing of deuterium for imaging glucose metabolism” Nat Biomed Eng. 2019 Apr 29; 3(5): 402-413.

• Shi L, Zheng C, Shen Y, Chen Z, Silveira ES, Zhang L, Wei M, Liu C, de Sena-Tomas C, Targoff K, Min W. “Optical imaging of metabolic dynamics in animals” Nat Commun. 2018 Aug 6; 9.

• Shi L, Shen Y, Min W. “Visualizing protein synthesis in mice with in vivo labeling of deuterated amino acids using vibrational imaging” APL Photonics. 2018 July 25; 3: 092401.

Tech Ventures Reference:

• IR CU19023, CU17300

• Licensing Contact: Beth Kauderer