期刊
CYTOMETRY PART A
卷 79A, 期 10, 页码 834-847出版社
WILEY
DOI: 10.1002/cyto.a.21127
关键词
in vivo flow cytometry; photoacoustic method; photothermal spectroscopy; circulating blood volume; contrast agent; dye
资金
- National Institute of Health [R01CA131164, R01 EB009230, R01EB000873, R21CA139373]
- National Science Foundation [DBI-0852737]
- Department of Defense [W88XWH-10-2-0130, W81XWH-10-BCRP-CA, W81XWH-11-1-0129]
- Russian Foundation for Basic Research [10-02-01354-a, 10-03-01018-a]
- Ministry of Science and Technology of Russian Federation [16.740.11.0471]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [0852737] Funding Source: National Science Foundation
Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue [TB]) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including Crystal Violet and Brilliant Green were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, and transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is safe for human, and its applications for studying the liver function are further highlighted. (C) 2011 International Society for Advancement of Cytometry
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