Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo

Authors

  • Dmitry A. Nedosekin,

    1. Winthrop P. Rockefeller Cancer Institute, Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #543, Little Rock, AR 72205, USA
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  • Mazen A. Juratli,

    1. Winthrop P. Rockefeller Cancer Institute, Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #543, Little Rock, AR 72205, USA
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  • Mustafa Sarimollaoglu,

    1. Winthrop P. Rockefeller Cancer Institute, Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #543, Little Rock, AR 72205, USA
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  • Christopher L. Moore,

    1. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
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  • Nancy J. Rusch,

    1. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
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  • Mark S. Smeltzer,

    1. Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
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  • Vladimir P. Zharov,

    1. Winthrop P. Rockefeller Cancer Institute, Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #543, Little Rock, AR 72205, USA
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  • Ekaterina I. Galanzha

    Corresponding author
    1. Winthrop P. Rockefeller Cancer Institute, Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #543, Little Rock, AR 72205, USA
    • Phone: (501) 603-1213
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Abstract

Circulating cells, bacteria, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early-stage of diseases. Here, we introduce novel CSF tests based on in vivo photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor-bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label-free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

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