期刊
CYTOMETRY PART A
卷 79A, 期 10, 页码 814-824出版社
WILEY
DOI: 10.1002/cyto.a.21106
关键词
circulating clots; in vivo flow cytometry; photoacoustic method; photothermal spectroscopy; label-free detection; stroke; thromboembolism; heart attack
资金
- National Institute of Health [R01CA131164, R01 EB009230, R21CA139373, R01EB000873]
- National Science Foundation [DBI-0852737]
- Department of Defense [W88XWH-10-2-0130, W81XWH-10-BCRP-CA, W81XWH-11-1-0129]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0852737] Funding Source: National Science Foundation
Conventional photothermal (PT) and photoacousic (PA) imaging, spectroscopy, and cytometry are preferentially based on positive PT/PA effects, when signals are above background. Here, we introduce PT/PA technique based on detection of negative signals below background. Among various new applications, we propose label-free in vivo flow cytometry of circulating clots. No method has been developed for the early detection of clots of different compositions as a source of thromboembolism including ischemia at strokes and myocardial infarction. When a low-absorbing, platelet-rich clot passes a laser-irradiated vessel volume, a transient decrease in local absorption results in an ultrasharp negative PA hole in blood background. Using this phenomenon alone or in combination with positive contrasts, we demonstrated identification of white, red, and mixed clots on a mouse model of myocardial infarction and human blood. The concentration and size of clots were measured with threshold down to few clots in the entire circulation with size as low as 20 mu m. This multiparameter diagnostic platform using portable personal high-speed flow cytometer with negative dynamic contrast mode has potential to real-time defining risk factors for cardiovascular diseases, and for prognosis and prevention of stroke or use clot count as a marker of therapy efficacy. Possibility for label-free detection of platelets, leukocytes, tumor cells or targeting them by negative PA probes (e.g., nonabsorbing beads or bubbles) is also highlighted.
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