Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo.

Photoacoustic flow cytometry is one of the most effective approaches to detect "alien" objects in the bloodstream, including circulating tumor cells, blood clots, parasites, and emboli. However, the possibility of detecting high-amplitude signals from these objects against the background of blood depends on the parameters of the laser pulse. So, the dependencies of photoacoustic signals amplitude and number on laser pulse energy (5-150 µJ), pulse length (1, 2, 5 ns), and pulse repetition rate (2, 5, 10 kHz) for the melanoma cells were investigated. First, the PA responses of a melanoma cell suspension in vitro were measured to directly assess the efficiency of converting laser light into an acoustic signal. After it, the same dependence with the developed murine model based on constant rate melanoma cell injection into the animal blood flow was tested. Both in vivo and in vitro experiments show that signal generation efficiency increases with laser pulse energy above 15 µJ. Shorter pulses, especially 1 ns, provide more efficient signal generation as well as higher pulse rates. A higher pulse rate also provides more efficient signal generation, but also leads to overheating of the skin. The results show the limits where the photoacoustic flow cytometry system can be effectively used for the detection of circulating tumor cells in undiluted blood both for in vitro experiments and for in vivo murine models.

Central pattern generator based on self-sustained oscillator coupled to a chain of oscillatory circuits.

We have proposed and studied both numerically and experimentally a multistable system based on a self-sustained Van der Pol oscillator coupled to passive oscillatory circuits. The number of passive oscillators determines the number of multistable oscillatory regimes coexisting in the proposed system. It is shown that our system can be used in robotics applications as a simple model for a central pattern generator (CPG). In this case, the amplitude and phase relations between the active and passive oscillators control a gait, which can be adjusted by changing the system control parameters. Variation of the active oscillator's natural frequency leads to hard switching between the regimes characterized by different phase shifts between the oscillators. In contrast, the external forcing can change the frequency and amplitudes of oscillations, preserving the phase shifts. Therefore, the frequency of the external signal can serve as a control parameter of the model regime and realize a feedback in the proposed CPG depending on the environmental conditions. In particular, it allows one to switch the regime and change the velocity of the robot's gate and tune the gait to the environment. We have also shown that the studied oscillatory regimes in the proposed system are robust and not affected by external noise or fluctuations of the system parameters. Moreover, using the proposed scheme, we simulated the type of bipedal locomotion, including walking and running.