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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA182840-01
Application #
8624122
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Ossandon, Miguel
Project Start
2014-03-20
Project End
2019-02-28
Budget Start
2014-03-20
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$295,405
Indirect Cost
$52,779
Name
Duquesne University
Department
None
Type
Organized Research Units
DUNS #
004501193
City
Pittsburgh
State
PA
Country
United States
Zip Code
15282