title: Nonlinear photoacoustic signal amplification from single targets in absorption background.
abstract: Photoacoustic (PA) detection of single absorbing targets such as nanoparticles or cells can be limited by absorption background. We show here that this problem can be overcome by using the nonlinear photoacoustics based on the differences in PA signal dependences on the laser energy from targets and background. Among different nonlinear phenomena, we focused on laser generation of nanobubbles as more efficient PA signal amplifiers from strongly absorbing, highly localized targets in the presence of spatially homogenous absorption background generating linear signals only. This approach was demonstrated by using nonlinear PA flow cytometry platform for label-free detection of circulating melanoma cells in blood backgroundin vitroandin vivo. Nonlinearly amplified PA signals from overheated melanin nanoclusters in melanoma cells became detectable above still linear blood background. Nonlinear nanobubble-based photoacoustics provide new opportunities to significantly (5-20-fold) increase PA contrast of single nanoparticles, cells, viruses and bacteria in complex biological environments.
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sarimollaoglu
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Nedosekin
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.
authors.forename: Yulian A
authors.initials: YA
authors.lastname: Menyaev
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.
authors.forename: Mazen A
authors.initials: MA
authors.lastname: Juratli
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
keywords: Photoacoustic imaging; blood; circulating tumor cells; flow cytometry; melanoma; nanobubbles; nonlinear phenomena