| Brain disorders bring the patient and family life a heavy burden as with its high incidence, high morbidity and high mortality. Electrophysiological nature of such diseases is excessive discharge of neurons synchronized, and its fundamental reason is the abnormal change of neuronal action potentials. Existing studies have shown that the electric field pulses(divided into microsecond, nanosecond and picosecond pulse depending on the pulse width) could regulate cell action potential, and then achieve corresponding biological effects. In recent years, ultrashort pulses with picosecond pulse width matching ultra wideband antenna has aroused great interest as its excellent directivity and accurate handling in the biomedical field of non-invasive treatment. The non-selective, non-targeted and non-invasive of the existing clinical could be overcomed, expected to provide a new strategy for the targeting non-invasive regulation of brain disorders.However, the mechanism study of biological effects on cells by picosecond pulsed electric field is still at an exploratory stage, and the regulation of neuronal action potentials by picosecond pulses is rather blank. Successfully preceding research work depends on the constraction of experimental platform, including the development of picosecond pulse generator and experimental electrode, is the basic work in this field. In this paper, with the support of the National Natural Science Foundation of China Youth Science Foundation of China(51307187), it completes the development of picosecond pulse generator and electrodes for neural regulation, and preliminary exploration in vivo on the regulation of picosecond pulse through animal experiments. The main achievements are:(1) Based on principles of traditional Marx circuit and introduced microstrip circuit theory, a portable compact picosecond pulse generator(18 cm × 18 cm × 4 cm) was developed. High stability and high repetition rate picosecond pulses with 1200 V peak voltage, 550 ps FWHM, 150 ps rise time and 0 ~ 10 k Hz repetition frequency could be generated on a 50? attenuator load.(2) Based on PSPICE circuit simulation software, Marx circuit model with introducted microstrip line was established, and the reason of waveform distortion was found through simulation analysis to optimize the output picosecond pulse waveform. Simulation and performance test results show that the series inductance can be used to eliminate fast jitter glitches picosecond pulse. Picosecond pulses with higher amplitude and narrower width could be generated based on the gradient transfer theory and using 10 p F capacitance sharpening in the terminal.(3) Two electrode devices for different cell experiments were developed based on microwave transmission theory and MEMS technology in this paper. One is for microscopic detection of multi-cellular substance, another for real-time observation under a microscope, both of which the desired picosecond pulsed electric field could be generated in cell suspensions. It lays a good basis work for the late mechanism exploration of neurons?(4) Based on experimental platform containing picosecond pulse generator and Cerebus multi-channel neural signal acquisition system, sports rat cortical neurons was used as experimental subject, the impact on neurual physiological activities by picosecond pulses with different parameters(amplitude, repetition rate, duration) was researched, revealing the relationship between neuronal action potentials firing and picosecond pulse parameters?In summary, portable picosecond pulse generators ware designed and developed based on microstrip transmission theory and the gradient transmission theory introduced in this paper. Multi-cell electrode and monocyte cell microfluidic system were developed based MEMS coaxial transmission theory and production process. And a preliminary research on motor cortex of rat neural regulation by picosecond pulses was done. It provides the necessary technical support for non-invasive treatment of brain disorders by picosecond pulse technology. |
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