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Fiber-optic multiphoton flow cytometry in whole blood and in vivo

Source: J. Biomed. Opt. 15, 047004 (2010); doi:10.1117/1.3463481

Published 26 July 2010

KEYWORDS and PACS
Keywords
PACS
PUBLICATION DATA
ISSN:
1553-9628 (online)
Publisher:
AIP is a member of CrossRef SPIE
Yu-Chung Chang
National Changhua University of Education, Department of Electrical Engineering, Changhua 500, Taiwan and University of Michigan, Center for Ultrafast Optical Science, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109

Jing Yong Ye
University of Michigan, Center for Ultrafast Optical Science, 2200 Bonisteel Boulevard and Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109

Thommey P. Thomas, Zhengyi Cao, and Alina Kotlyar
University of Michigan, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109

Eric R. Tkaczyk
University of Michigan, Center for Ultrafast Optical Science, 2200 Bonisteel Boulevard and Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109

James R. Baker, Jr.
University of Michigan, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109

Theodore B. Norris
University of Michigan, Center for Ultrafast Optical Science, 2200 Bonisteel Boulevard and Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109
Circulating tumor cells in the bloodstream are sensitive indicators for metastasis and disease prognosis. Circulating cells have usually been monitored via extraction from blood, and more recently in vivo using free-space optics; however, long-term intravital monitoring of rare circulating cells remains a major challenge. We demonstrate the application of a two-photon-fluorescence optical fiber probe for the detection of cells in whole blood and in vivo. A double-clad fiber was used to enhance the detection sensitivity. Two-channel detection was employed to enable simultaneous measurement of multiple fluorescent markers. Because the fiber probe circumvents scattering and absorption from whole blood, the detected signal strength from fluorescent cells was found to be similar in phosphate-buffered saline (PBS) and in whole blood. The detection efficiency of cells labeled with the membrane-binding dye 1,1[prime]-dioctadecyl-3,3,3[prime],3[prime]-tetramethylindoldicarbocyanine, 4-chlorobenzenesulfonate (DiD) was demonstrated to be the same in PBS and in whole blood. A high detection efficiency of green fluorescent protein (GFP)–expressing cells in whole blood was also demonstrated. To characterize in vivo detection, DiD-labeled untransfected and GFP-transfected cells were injected into live mice, and the cell circulation dynamics was monitored in real time. The detection efficiency of GFP-expressing cells in vivo was consistent with that observed ex vivo in whole blood. ©2010 Society of Photo-Optical Instrumentation Engineers
History: Received 9 June 2009; revised 31 March 2010; accepted 14 May 2010; published 26 July 2010
Permalink: http://dx.doi.org/10.1117/1.3463481

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