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 background in vitro and in 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.

Spaser as a biological probe

“…A high speed (1,000 cells per minute) PA flow cytometry2223 demonstrated a high labelling efficiency through significant (10–50-fold) signal increase from individual cells loaded with spasers (Supplementary Fig. 12).…”

Parametrical Tuning of Twisting Generators

“…A Pseudorandom Number Generators (PRNG) are well-known techniques with broad applications in such areas as cryptography (Tusnoo et al, 2003;Ozturk et al, 2004;Panneton et al, 2006), simulation of stochastic processes (Entacher, 1998), comprehensive testing of technical systems (Leeb and Wegenkittl, 1997;Park and Miller, 1998), medical (Menyaev and Zharov, 2006a;2006b;Menyaev and Zharova, 2006;2013;2016;Sarimollaoglu et al, 2014;Cai et al, 2016a;2016b) and biological research (Wiese et al, 2005;Leonard and Jackson, 2015;Juratly et al, 2015;2016) and others (Rababbah 2004;2007;Politano et al, 2014;2016;Riguzzi, 2016). In these publications, the concept of uniform random numbers in PRNG actively uses the operations of bit logic.…”

Nonlinear optoacoustic readings from diffusive media at near‐infrared wavelengths

“…However, recent reports suggested nonlinear optoacoustic intensity readings in response to increasing light fluence on microscopic specimens . Nonlinear signals have been collected from exogenous dyes, nanoparticles and chromophores , and different mechanisms have been proposed responsible for the nonlinear behavior, including the formation of nanobubbles , changes of thermophysical parameters, such as thermal expansion coefficient, due to local temperature enhancement around particles at high laser fluence , saturation of the absorption coefficient or evaporation of fluids surrounding heated particles (250°C‐355°C for water) . It is understood that different phenomena may contribute to the generation of nonlinear optoacoustic responses, depending on the amount of energy or power utilized and the medium interrogated.…”