Circulating tumor cells (CTCs) are those cells that have separated from solid tumors, spreading throughout the body with potential to create other tumors. Thus, CTCs may be indicators of metastasis. Their detection may provide clinicians with heretofore unavailable information about disease state in advanced cancer patients, enabling proper management of therapy. Additionally, isolation of CTCs may allow scientists to investigate fundamental questions about cancer biology. The investigators developed a photoacoustic flowmeter to detect and isolate circulating melanoma cells (CMCs) present in blood samples of melanoma patients. Unlike conventional flow cytometry that relies on laser reflectance and induced fluorescent signals, this device generates photoacous- tic waves in pigmented melanoma cells. These photoacoustic waves are specific to pigmented cells, such as melanoma, creating robust laser induced acoustic signals that attenuate very little in comparison to optical signals like fluorescence. Photoacoustic flowmetry allows detection of single CMCs in blood samples. In the photoacoustic flowmeter, rather than continuous flow, the blood cell suspension is separated into microliter droplets separated by similar volumes of air. This arrangement of two phase flow allows isolation of any CMCs in small volumes, enabling capture and isolation for further study. Using a group of Stage IV melanoma patients, the investigators will perform molecular assays to investigate proliferation index, epithelial-mesenchymal transition, and other issues that will pro- vide new insight into the process of metastasis. This new information may be used to develop means to interrupt metastatic disease. Finally, the investigators will create a statistical model, tested on 80 early stage melanoma patients, that wil determine the association of CMCs with the transition to metastasis, enabling proactive clinical management.

Public Health Relevance

Photoacoustic detection, capture, and analysis of circulating melanoma cells Circulating tumor cells have been correlated to metastatic disease, though little is known about their biology due to the difficulty in capturing them. We have developed a photoacoustic flowmeter to detect and isolate circulating melanoma cells in human blood samples. Using this technology, we will perform comparative analysis on circulating melanoma cells and those melanoma cells from solid tumors to gain insight into their biological and molecular nature, as well as performing a study on early stage melanoma patients to see if CTCs predict time to metastasis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Instrumentation and Systems Development Study Section (ISD)
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Ossandon, Miguel
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Duquesne University
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United States
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Bhattacharyya, Kiran; Goldschmidt, Benjamin S; Viator, John A (2016) Detection and capture of breast cancer cells with photoacoustic flow cytometry. J Biomed Opt 21:87007
Goldschmidt, Benjamin S; Viator, John A (2015) Capture and Isolation of Circulating Melanoma Cells Using Photoacoustic Flowmetry. Methods Mol Biol :
Bhattacharyya, Kiran; Eshein, Adam; Chandrasekhar, Anand et al. (2015) Quantitative photoacoustics to measure single cell melanin production and nanoparticle attachment. Phys Med Biol 60:3081-96