Principal Investigator

Lev T
Perelman
Awardee Organization

Beth Israel Deaconess Medical Center
United States

Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Spectro-Holographic Instrument for Dynamic Sensing of Cancer Progression

In this application we propose to develop a native contrast optical spectroscopic sensing approach that identifies and characterizes subcellular structures and quantifies their properties when cells undergo precancerous alterations, by using light scattering spectra as native optical biomarkers. Such a technique would enable simultaneous labeling of large number of subcellular and subnuclear structures without the use of stains and would be of great value for studying early cancer progression. The absence of stains also makes such methods easy to implement in time-course cancer progression studies and would be amenable for in vivo observations in humans. Although cellular alterations in organelle and nuclear structure are readily observed and studied in cancer, there are fundamental limitations in existing imaging techniques that prevent the study of very early stage pre-cancerous alterations. In contrast to dysplastic cellular alterations such as nuclear enlargement and organization, the earliest stages of carcinogenesis have much more subtle alterations that are not easily discernible with standard microscopy techniques. Perhaps the most often used imaging tool for observing cellular structure is fluorescence microscopy. It can achieve targeted contrast for specific organelles or proteins, however imaging in live cells remains limited to just a few types of fluorophores and therefore structure types. Although recently developed optogenetic methods and new live cell fluorescent probes have significantly improved the utility of fluorescence in living systems, the method is inherently limited to observing a few types of structures at relatively short time scales. An even more substantial limitation of conventional optical imaging is that it is subject to the diffraction limit and cannot discern the properties of cellular structures that are significantly smaller than a wavelength. On the other hand, electron microscopy imaging methods are destructive, involve extensive manipulations with the sample, and cannot be utilized in living systems. In order to overcome the limitations of both methods, a technique that is based on an entirely different physical principle is required. This method should ideally identify all important cellular structures in live cells, while simultaneously dynamically quantifying their properties when cells undergo pre-cancerous alterations.

Publications

  • Coughlan MF, Sawhney MS, Pleskow DK, Sheil CJ, GI Light Scattering Group, Qiu L, Perelman LT. Measuring Droplets Expelled During Endoscopy to Investigate COVID-19 Transmission Risk. Gastroenterology. 2021 Nov;161(5):1702-1704.e3. Epub 2021 Jul 16. PMID: 34280387
  • Qiu L, Zhang L, Turzhitsky V, Khan U, Zakharov Y, Kantekure K, Vitkin E, Itzkan I, Pleskow DK, Sawhney M, Berzin TM, Goldsmith JD, Perelman LT. Multispectral Endoscopy with Light Gating for Early Cancer Detection. IEEE journal of selected topics in quantum electronics : a publication of the IEEE Lasers and Electro-optics Society. 2019 Jan-Feb;25. (1). Epub 2018 Jul 9. PMID: 31244520
  • Rodgers JL, Garrison SM, O'Keefe P, Bard DE, Hunter MD, Beasley WH, van den Oord EJCG. Responding to a 100-Year-Old Challenge from Fisher: A Biometrical Analysis of Adult Height in the NLSY Data Using Only Cousin Pairs. Behavior genetics. 2019 Sep;49(5):444-454. Epub 2019 Aug 7. PMID: 31392459
  • Pleskow DK, Zhang L, Turzhitsky V, Coughlan MF, Khan U, Zhang X, Sheil CJ, Glyavina M, Chen L, Shinagare S, Zakharov YN, Vitkin E, Itzkan I, Perelman LT, Qiu L. Coherent confocal light scattering spectroscopic microscopy evaluates cancer progression and aggressiveness in live cells and tissue. ACS photonics. 2021 Jul 21;8(7):2050-2059. Epub 2021 Jun 20. PMID: 34485615
  • Coughlan MF, Perelman LT. Label-free characterization of organoids with quantitative confocal Raman spectral imaging. Cell reports methods. 2023 Apr 13;3(4):100457. doi: 10.1016/j.crmeth.2023.100457. eCollection 2023 Apr 24. PMID: 37159664
  • Pleskow DK, Sawhney MS, Upputuri PK, Berzin TM, Coughlan MF, Khan U, Glyavina M, Zhang X, Chen L, Sheil CJ, Cohen JM, Vitkin E, Zakharov YN, Itzkan I, Zhang L, Qiu L, Perelman LT. In vivo detection of bile duct pre-cancer with endoscopic light scattering spectroscopy. Nature communications. 2023 Jan 7;14(1):109. PMID: 36611024
  • Sheil CJ, Khan U, Zakharov YN, Coughlan MF, Pleskow DK, Sawhney MS, Berzin TM, Cohen JM, Glyavina M, Zhang L, Itzkan I, Perelman LT, Qiu L. Two-photon polymerization nanofabrication of ultracompact light scattering spectroscopic probe for detection of pre-cancer in pancreatic cyst. Optics and lasers in engineering. 2021 Jul;142. Epub 2021 Mar 20. PMID: 34305200
  • Turzhitsky V, Zhang L, Horowitz GL, Vitkin E, Khan U, Zakharov Y, Qiu L, Itzkan I, Perelman LT. Picoanalysis of Drugs in Biofluids with Quantitative Label-Free Surface-Enhanced Raman Spectroscopy. Small (Weinheim an der Bergstrasse, Germany). 2018 Nov;14(47):e1802392. Epub 2018 Oct 7. PMID: 30369072
  • Qiu L, Zhang L, Horowitz GL, Turzhitsky V, Coughlan MF, Glyavina M, Khan U, Zakharov YN, Vitkin E, Itzkan I, Perelman LT. Rapid detection and identification of bacteria directly from whole blood with light scattering spectroscopy based biosensor. Sensors and actuators. B, Chemical. 2021 Nov 1;346. Epub 2021 Jul 24. PMID: 34483482
  • Pettinato G, Coughlan MF, Zhang X, Chen L, Khan U, Glyavina M, Sheil CJ, Upputuri PK, Zakharov YN, Vitkin E, D'Assoro AB, Fisher RA, Itzkan I, Zhang L, Qiu L, Perelman LT. Spectroscopic label-free microscopy of changes in live cell chromatin and biochemical composition in transplantable organoids. Science advances. 2021 Aug 18;7. (34). Print 2021 Aug. PMID: 34407934
  • Coughlan MF, Sawhney MS, Pleskow DK, Khan U, Silva-Santisteban A, Ahmed A, Zhang X, Glyavina M, Chen L, Upputuri PK, Zakharov YN, Zhang L, Qiu L, Perelman LT. Biopsy channel of the endoscope as a potential source of infectious droplets during GI endoscopy. Gastrointestinal endoscopy. 2022 Nov;96(5):764-770. Epub 2022 Jun 18. PMID: 35724696