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Published December 21, 2016 | Supplemental Material + Published
Journal Article Open

In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells


Metastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature.

Additional Information

© 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Received 12 October 2016; Accepted 23 November 2016; Published 21 December 2016. We thank Prof. J. Ballard for editing the manuscript and Prof. J.-Y. Shao for helping with cell culturing. This work was supported in part by US National Institutes of Health (NIH) grants R01 CA186567 (NIH Director's Transformative Research Award) and DP1 EB016986 (NIH Director's Pioneer Award) to L.V.W., and US National Science Foundation IDBR awards 1255930 to L.V.W. and 1255921 to J.Z. Author Contributions: Y.H., L.W. and J.S. contributed equally. Y.H., L.W., J.S. and L.V.W. conceived and designed the study. Y.H., L.W., J.Y. and C.-H.H. constructed the system. Y.H., L.W. and J.S. performed the experiments and analyzed the data. R.Z. performed cell culturing. L.V.W. initiated and supervised the whole study. All authors wrote the manuscript. Competing interests: L.V.W. has a financial interest in Microphotoacoustics, Inc., which, however, did not support this work. The remaining authors declare no competing financial interest.

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