Our goal is to exploit endogenous sources of optical contrast, including scattering and endogenous fluorescence and develop an approach that enables us to enumerate cells or cell clusters of interest in flowing blood samples, ultimately in vivo. Georgakoudi was a key member of the team that developed the initial version of this technology while she was at the Massachusetts General Hospital, which relied on the detection of cells expressing fluorescent proteins1, 2. While our initial experiments continued to build on this concept to assess the role of circulating tumor cells in metastasis3, we performed a series of studies to highlight the potential of this approach relying on endogenous scattering 4-6. More recently, we have shown that machine-learning approaches can truly enable implementation of this technique to identify circulating tumor cell clusters in whole-blood samples flowing through microfluidic devices 7, 8. Our current efforts focus on using this technology to detect interacting CAR-T and B cells to monitor treatment and circulating tumor cell clusters in the blood of patients with metastatic breast cancer.

Key Relevant Publications
  1. Georgakoudi I, Solban N, Novak J, Rice WL, Wei X, Hasan T, Lin CP. In vivo flow cytometry: a new method for enumerating circulating cancer cells. Cancer Res. 2004;64(15):5044-7. Epub 2004/08/04. doi: 10.1158/0008-5472.CAN-04-105864/15/5044 [pii]. PubMed PMID: 15289300.
  2. Novak J, Georgakoudi I, Wei X, Prossin A, Lin CP. In vivo flow cytometer for real-time detection and quantification of circulating cells. Opt Lett. 2004;29(1):77-9. Epub 2004/01/15. PubMed PMID: 14719666; PMCID: 2801600.
  3. Hwu D, Boutrus S, Greiner C, DiMeo T, Kuperwasser C, Georgakoudi I. Assessment of the role of circulating breast cancer cells in tumor formation and metastatic potential using in vivo flow cytometry. J Biomed Opt. 2011;16(4):040501. Epub 2011/05/03. doi: 10.1117/1.3560624. PubMed PMID: 21529063.
  4. Greiner C, Hunter M, Huang P, Rius F, Georgakoudi I. Confocal backscattering spectroscopy for leukemic and normal blood cell discrimination. Cytometry A. 2011;79(10):866-73. Epub 2011/07/12. doi: 10.1002/cyto.a.21095. PubMed PMID: 21744493.
  5. Hsiao A, Hunter M, Greiner C, Gupta S, Georgakoudi I. Noninvasive identification of subcellular organization and nuclear morphology features associated with leukemic cells using light-scattering spectroscopy. J Biomed Opt. 2011;16(3):037007. Epub 2011/04/05. doi: 10.1117/1.3562925. PubMed PMID: 21456879; PMCID: 3081866.
  6. Lyons J, Polmear M, Mineva ND, Romagnoli M, Sonenshein GE, Georgakoudi I. Endogenous light scattering as an optical signature of circulating tumor cell clusters. Biomed Opt Express. 2016;7(3):1042-50. doi: 10.1364/BOE.7.001042. PubMed PMID: 27231606; PMCID: PMC4866447.
  7. Vora N, Shekhar P, Esmail M, Patra A, Georgakoudi I. Label-free flow cytometry of rare circulating tumor cell clusters in whole blood. Sci Rep. 2022;12(1):10721. Epub 20220624. doi: 10.1038/s41598-022-14003-5. PubMed PMID: 35750889; PMCID: PMC9232518.
  8. Vora N, Shekar P, Hanulia T, Esmail M, Patra A, Georgakoudi I. Deep learning-enabled detection of rare circulating tumor cell clusters in whole blood using label-free, flow cytometry. Lab Chip. 2024;24(8):2237-52. Epub 20240416. doi: 10.1039/d3lc00694h. PubMed PMID: 38456773; PMCID: PMC11019838.