Program Official

Principal Investigator

Lev T
Awardee Organization

Beth Israel Deaconess Medical Center
United States

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

Isolation and Assessment of Blood-Circulating Cancer Exosomes with LSS and SERS Lab on a Chip Optical Spectroscopic Instrument

Shed into the peripheral circulation from a primary tumor, circulating tumor cells (CTCs) are limited by their extremely sparse concentrations in blood. In contrast, molecular markers secreted by tumor cells into the vasculature are present in much higher concentrations and could provide important insight on cancer cell biology and predictive biomarkers for early detection, progression and metastasis. These markers, including soluble proteins, cell-free DNA (cfDNA), and circulating microvesicles and exosomes have been shown to contain valuable information on the molecular state of often difficult to access tumor sites. Unfortunately, the source of the soluble proteins found in blood cannot be determined, resulting in the high false-positive rates, while significantly more specific cfDNA often reflect the dying or apoptotic cells. Exosomes, small membrane vesicles of endocytic origin, show the greatest potential as an easily accessible biomarker for early cancer detection and monitoring due to their unique properties, including their stability in biological fluids and their potential to be efficiently isolated. Cancer cells release more exosomes than normal cells and exosomes secreted from tumor cells can promote tumor progression, survival, invasion and angiogenesis. In this application we propose to develop an optical spectroscopic technique, which combines light scattering spectroscopy (LSS) and surface enhanced Raman spectroscopy (SERS) for highly rigorous isolation and assessment of blood-circulating cancer exosomes for early cancer detection in a rapid and inexpensive lab-on-a-chip system. As it is shown in this application, not only LSS can separate exosomes from microvesicles, the capability not available at the moment, but it also can differentiate various types of exosomes originated in different organs of the digestive tract, while SERS is capable of differentiating exosomes secreted by cancerous and normal cells of the same organ.


  • 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
  • Qiu L, Chuttani R, Pleskow DK, Turzhitsky V, Khan U, Zakharov YN, Zhang L, Berzin TM, Yee EU, Sawhney MS, Li Y, Vitkin E, Goldsmith JD, Itzkan I, Perelman LT. Multispectral light scattering endoscopic imaging of esophageal precancer. Light, science & applications. 2018 Apr 6;7:17174. doi: 10.1038/lsa.2017.174. eCollection 2018. PMID: 30839534
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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