Shock waves have been established as a safe and effective treatment for a wide range of diseases. Research groups worldwide are working on improving shock wave technology and developing new applications of shock waves to medicine and biology. The passage of a shock wave through soft tissue, fluids, and suspensions containing cells may result in acoustic cavitation i.e., the expansion and violent collapse of microbubbles, which generates secondary shock waves and the emission of microjets of fluid. Cavitation has been recognized as a significant phenomenon that produces both desirable and undesirable biomedical effects. Several studies have shown that cavitation can be controlled by emitting two shock waves that can be delayed by tenths or hundreds of microseconds. These dual-pulse pressure pulses, which are known as tandem shock waves, have been shown to enhance in vitro and in vivo urinary stone fragmentation, cause significant cytotoxic effects in tumor cells, delay tumor growth, enhance the bactericidal effect of shock waves and significantly increase the efficiency of genetic transformations in bacteria and fungi. This article provides an overview of the basic physical principles, methodologies, achievements and potential uses of tandem shock waves to improve biomedical applications.

The generator of two focused successive (tandem) shock waves (FTSW) in water produced by underwater multichannel electrical discharges at two composite electrodes, with a time delay between the first and second shock waves of 10 \(\upmu \)s, was developed. It produces, at the focus, a strong shock wave with a peak positive pressure of up to 80 MPa, followed by a tensile wave with a peak negative pressure of up to \(-80\) MPa, thus generating at the focus a large amount of cavitation. Biological effects of FTSW were demonstrated in vitro on hemolysis of erythrocytes and cell viability of human acute lymphoblastic leukemia cells as well as on tumor growth delay ex vivo and in vivo experiments performed with B16 melanoma, T-lymphoma, and R5-28 sarcoma cell lines. It was demonstrated in vivo that FTSW can enhance antitumor effects of chemotherapeutic drugs, such as cisplatin, most likely due to increased permeability of the membrane of cancer cells induced by FTSW. Synergetic cytotoxicity of FTSW with sonosensitive porphyrin-based drug Photosan on tumor growth was observed, possibly due to the cavitation-induced sonodynamic effect of FTSW.

We explored basic optical and electrical characteristics of a positive corona-like discharge produced in conductive aqueous solutions by periodic high-voltage pulses. Emission spectra of the discharge were acquired in a needle-to-plate electrode geometry and analysed in the UV-vis-NIR spectral range with nanosecond time resolution for the solution conductivity of 100 and 500 mu S cm(-1). The most important emission features are due to electronic excitation of H-I, O-I, O-II and OH species. We found evidence of significant time-dependent line-shape broadening of selected H-I and O-I transitions. The observed broadening is attributed to the dynamic Stark and pressure broadening mechanisms and significantly increases with the aqueous solution conductivity. Electron densities were estimated by fitting a single Voigt peak function to the observed H alpha profiles, and can reach as much as n(e) congruent to 4 x 10(18) cm(-3) (t(D) = 300 ns at 100 mu S cm(-1) solution conductivity) and n(e) congruent to 5 x 10(18) cm(-3) (t(D) = 1 mu s at 500 mu S cm(-1)). Temporal evolution of the partially resolved rotational structure of the OH emission reaches a maximum during the discharge decay, with the onset significantly delayed with respect to the streamer ignition.

We explored basic optical and electrical characteristics of a positive corona-like discharge produced in conductive aqueous solutions by periodic high-voltage pulses. Emission spectra of the discharge were acquired in a needle-to-plate electrode geometry and analysed in the UV–vis–NIR spectral range with nanosecond time resolution for the solution conductivity of 100 and 500 µS cm−1. The most important emission features are due to electronic excitation of HI, OI, OII and OH species. We found evidence of significant time-dependent line-shape broadening of selected HI and OI transitions. The observed broadening is attributed to the dynamic Stark and pressure broadening mechanisms and significantly increases with the aqueous solution conductivity. Electron densities were estimated by fitting a single Voigt peak function to the observed Hα profiles, and can reach as much as ne ≅ 4 × 1018 cm−3 (tD = 300 ns at 100 µS cm−1 solution conductivity) and ne ≅ 5 × 1018 cm−3 (tD = 1 µs at 500 µS cm−1). Temporal evolution of the partially resolved rotational structure of the OH emission reaches a maximum during the discharge decay, with the onset significantly delayed with respect to the streamer ignition.

Objectives: The shock wave is used for the treatment of kidney stones, eventually of gall stones, for more than 20 years.It is a pressure wave, which breaks through soft tissues easily and it is possible to focus it into a small volume.The excellent results of the treatment of concrements led to considerations about another usage of the shock wave.The research is now concentrated on the possibility of the damage to tumour tissues.Methods: In contrast to concrements tumour tissues are not different from healthy tissues as for their acoustic attributes.That is why a new source of shock waves was used in this work.The source allows generating two successive shock waves focused into a common focus, so-called tandem shock waves.The biological effects of the tandem shock waves generated by the new source on rats hepatic tissue and rabbit femoral muscle in vivo were studied in this work.The damage is demonstrated by magnetic resonance imaging.Results: MR images showed tissue damage in focus.There was damage of the liver tissue, muscle and also stomach wall.Conclusions: We found that the tandem shock waves are able to damage the acoustically homogeneous soft tissue in the focus, i.e. in the depth.In tissues in front of the focus, there is, however, no damage (Fig. 10, Ref. 15).

Cavitation associated with the generation of shock waves in water was examined. To study these processes, a tandem shock wave generator, which generates two cylindrical pressure waves focused by a metallic parabolic reflector to a common focal region, was developed. The temporal evolution of cavitation generated by shock waves at the focal region was determined experimentally using high-temporal-resolution microphotography for a certain time delay between the first and second shock waves. Observation of the focal area also showed jetting cavitation bubbles with diameters of 100 μm without presence of any rigid boundary. A theoretical model that provides analytical expressions for the temporal evolution of the pressure inside the cavitation bubbles and parameters of the pressure waveform of the second shock wave at the focal area was used to improve the same measurement by PVDF sensor gauges. On the basis of this model, the amplitudes of the compression and rarefaction parts of the second shock wave were determined to be 135 MPa and on the order of -50 MPa, respectively. An estimation of the bubble internal gas concentration and temperature during cavitation development was made. The calculated peak internal temperature reached 1240 K.

Shock waves, pressure waves manifested as a sharp increase in positive pressure followed by a decrease and the negative part of the wave, are not only used to treat concrements in medicine. Recently, research has been focused on the possibility of their use for damaging the tumour tissue. In contrast to concrements, which are different from the surrounding tissue by their acoustic impedance, the tumour tissue has the same acoustic impedance as the surrounding soft tissue. Therefore, we have developed a new source of shock waves, which is based on the principle of multichannel discharge. This new source generates two successive shock waves (tandem shock waves). The first shock creates acoustic non-homogeneity and cavitations in the tissue, and the second shock is damped in it. In this work we demonstrated the effect of tandem shock waves on the muscle tissue in depth. The damage is shown on the images from the magnetic resonance imaging and histological sections. In the further part of the experiment, we investigated the in vivo effects of tandem shock waves in combination with Photosan and cisplatin on the tumour tissue. The application of tandem shock waves resulted in the inhibition of tumour growth, compared with controls, in both parts of the experiment. The largest inhibition effect was observed in the groups of tandem shock waves combined with Photosan and in the second part with cisplatin.

Summary form only given. The success of the extracorporeal shock wave lithotripsy in non-invasive treating patients with stone deceases (mostly kidney stones) stimulated research on applications of focused shock waves in other branches of medicine such as for noninvasive treatment of cancer tissues and a targeted drug delivery. However, there is a fundamental difference in treatment of kidney stones and in a possible treatment of cancer tissues. The stone represents relatively strong acoustical non-homogeneity in comparison with the surrounding liquid and soft tissues. Moreover, there is no acoustical non-homogeneity between cancer and healthy tissues. Therefore, great attention is paid to the investigation of the role of cavitations produced by focused shock waves. Collapsing cavitations can create secondary, very short wavelength shock waves, which can interact with cell scale structures. Recently, we have developed a generator of two successive (tandem) shock waves focused to a common focal point. The first shock creates at the focal region an acoustical non-homogeneity and cavitations, and the second shock dissipate on it. We have found that at time interval of 10-15 μs between the shocks the second, originally pressure wave, reaches the focus as a rarefaction wave. Amplitude of the pressure wave is up to 100 MPa, while the amplitude of the rarefaction wave falls down to -25 MPa, producing thus at the focus a large number of cavitations, which are considered to play the main role in cell membranes damage.The purpose of this work was to demonstrate possibility to localize in vivo the action of the focused tandem shock waves at predictable region in acoustically homogenous medium such as soft tissues are. Rabbit's thigh muscles were exposed in vivo to the focused tandem shocks with a fixed time delay between the waves of 10 μs. Trials with exposure to 1600 shocks have been done. The MR images of rabbit thighs after exposure to the tandem shock wa- es clearly demonstrated targeted lesions deep inside the soft tissue. These results are important for further development of this technique focused on potential application of tandem shock waves for cancer treatment (e.g., enhancement of chemotherapy efficiency induced by tandem shock waves by increasing permeability of tumor cells membranes to cytostatic drugs).

UV radiation in the 200-300 nm wavelength range with doses of several mJ/cm2 is known to cause lethal damage of cells. Amongst UV effects on bacteria is the dimerization of thymine bases in their DNA strands. This inhibits the ability of bacteria to replicate properly. The results obtained using the emission spectroscopy showed a radiation from the pulsed corona discharge in water in a wide range of wavelengths (200-1000 nm), which is dominated by the spectral lines of hydrogen and oxygen atom and by emission from OH radical. Electron density above 1018 cm-3 in the streamer discharge has been determined from the Halpha spectral line profile. With increasing water conductivity stronger radiation and higher electron density in the streamer discharge have been determined (above 1019 cm-3). Quantitative analysis of ultraviolet radiation from the pulsed corona discharge in water performed by the potassium ferrioxalate actinometry revealed that significant UV emission from the discharge occurs with increasing solution conductivity and the pulse radiant power of the emitted UV radiation could reach levels of the order of tens to hundreds of Watts per pulse in the range of solution conductivity of 100-500 muS/cm. This radiant power corresponds to UV radiation intensity of the order 0.1-10 mW/cm2. This is a significantly higher intensity level than reported for non- equilibrium air plasma where UV radiation does not play a significant direct role in the sterilization process. This indicates that UV radiation may play an important role in the bacterial inactivation by the corona discharge in water. In this work, the effects of pulsed corona discharge in water on the inactivation of Gram-negative bacteria Escherichia coli and Gram-positive bacteria Enterococus faecalis are investigated. The role and contribution of ultraviolet radiation from the discharge in the overall bacterial inactivation by the - lectrical discharge in water of two different solution conductivity (200 and 500 muS/cm) are discussed.

We have investigated biological effects of two successive (tandem) shock waves focused to a common focal region on soft animal tissues, including cancer tissues "in vivo" and cancer cells "ex vivo". The tandem shock waves have been produced by our formerly developed shock wave generator where two cylindrical pressure waves are focused by a metallic parabolic reflector to a common focal region and the second shock can be switched on with a different time delay after the first one. The idea on application of the tandem shock waves is to localize the action of the shocks at a predictable region in an initially acoustically homogenous medium such as cancer tissues are. The first shock creates in the tissue some acoustical non homogeneity and cavitations, and the second shock dissipate on it, similarly as it is in the case of the lithotripsy of kidney stones. We have found that at some time interval between the shocks (10-15 Icircfrac14s) the second, originally pressure wave, reaches the focus as a rarefaction wave that produces a large number of cavitations. Collapsing cavitations create secondary, very short wavelength shocks which can interact with cell scale structures. We have demonstrated that the tumors from cancer cells exposed to the tandem shocks grow much slowly. We know that the tandem shocks locally injure a healthy tissue of a rabbit liver . In this work we will present results on synergistic effect of the tandem shocks and hematoporphyrin on the growth rate of tumors on laboratory rats. Preliminary experiments show that the combined therapy of shock waves with hematoporphyrin (i.e., sonotherapy) should be applied in the initial stage of the tumor development.

Summary form only given. We have developed a shock wave generator where two cylindrical pressure waves are focused to a common focal region by a metallic parabolic reflector, and the waves can be switched on with a different time delay. Interaction of two successive shock waves (tandem shocks) in water focused to a common focal point was investigated. Amplitude of the of the pressure wave reaches up to 100 MPa at the focus, while the amplitude of the rarefaction wave falls down to -25 MPa (well above the cavitation threshold), producing thus numerous cavitations. Schlieren photography of the focal region demonstrated creation of a very complex pressure field with many secondary spherical short wavelength shocks that originate in collapsing cavitations. These secondary shocks can interact with cell scale structures and they are considered to play the main role in cell membranes damage when organic tissue is exposed to the shock waves. Therefore, we are interested in the waveform and the pressure amplitude of these secondary shocks with an ultimate goal in enhancement of cancer treatment efficiency by activation of sonosensitizers based on the effects of the collapsing cavitations. In this work cavitations dynamics induced by the tandem shock waves in water is investigated in more detail. It was demonstrated that the acoustical non homogeneity created in water by the first wave strongly modifies propagation of the second one. Measurements of the pressure waveforms by PVDF shock gauges at the focus demonstrated that at some time delays between shocks the second wave reaches the focus as a rarefaction wave producing thus a large number of cavitations. To determine a gas pressure in the cavitations, strong electric field in the focal area will be applied to generate electrical discharges inside the cavitations. Breakdown voltage with known diameter of the cavitations can provide information about the gas density in the fully developed cavitations. From observation of a - peed of the cavitations collapse with the knowledge of the gas density a temperature inside collapsing cavitations and the pressure of the secondary shock waves can be determined.

Non-equilibrium plasma generated by electrical discharges in liquids initiate various chemical and physical processes that can be potentially utilized in different environmental, biological or medical applications. These processes include high electric field, ultraviolet radiation, overpressure shock waves and, of particular importance, formation of various reactive chemical species such as radicals (OH, H, O) and molecular species (H2O2, H2, O3), among which OH radicals and hydrogen peroxide are the most important for oxidation processes. The magnitude of the contributions of the individual effects in the decontamination or microbial inactivation processes strongly depends upon the energy of the discharge and also on the solution conductivity. An increase in the solution conductivity is connected with a higher concentration of ions in the liquid, which strongly alter the propagation of the streamer channel in water by compensating the space charge electric field on the streamer head. Thus, higher conductivity results, on the one hand, in a larger discharge current due to lower resistivity of liquid media, and, on the other hand, in a shortening of the streamer channel length due to faster compensation of space charge electric field on the streamer head by ions in the liquid. This results in a higher power density in the discharge channel and a higher plasma temperature and higher UV radiation. Hydrogen peroxide as the most abundant chemical species directly produced by the discharge in water is often utilized in Fenton's reaction to increase the plasmachemical efficiency of the removal of organic compounds by addition of ferrous salts into treated water. There is also evidence about contribution of H2O2 in bacterial inactivation by electrical discharge in water. In the present study, the role of solution conductivity in the hydrogen peroxide production by the pulsed corona discharge in water generated using point to plane geometry of electrodes is investigated. The free radical scavenging property of DMSO and phenol is used to determine the initial rate of formation of H2O2 by the pulsed corona discharge. The influence of UV radiation of the discharge and the effect of H2 and O2 on the production of hydrogen peroxide will be discussed.

Interaction of two successive shock waves (tandem shocks) in water focused to a common focal point has been investigated. Amplitude of the compression part of the wave s as high as 100 MPa, while amplitude of the dilution part of the wave reaches down to -25 MPa in the focus. At that underpressure numerous cavitations are produced. It was demonstrated that the acoustical inhomogeneity created in water by the first wave strongly modifies propagation of the second one. Measurements of waveforms by PVDF shock gauges at the focus indicate that the second wave is strongly attenuated at some time delays between shocks. At time delays in the interval 50-500 mus the second wave is totally damped at the focus. Schlieren photography of the focal region demonstrates that the interaction of two successive shocks results in creation of a very complex pressure field at the focus to which contribute many secondary spherical short wavelength shocks that originate in collapsing cavitations. The tandem shock waves can be potentially applied to sonodynamic treatment of cancer tumors. Effect of the tandem shock waves on melanoma cells B16 has been investigated. Micro photographs of cells demonstrate that even a small number of shocks (100) result in perforation of cell membranes. At present an enhancement of treatment efficiency by the activation of sonosensitizers combined with the perforation of cell membranes is studied.

A short liposome exposure to ultrasonic waves with the intensity of I = 2 W/cm2 at frequency f = 1 MHz was found to be a sufficient tool for liposome opening. In addition, shock-wave proved to be sufficient also for liposome content release. Both methods are useful tools to be used as control mechanisms for drug delivery systems based on liposomes. However, due to better focusing and low non-thermal side effects, shock-waves probably have a markedly higher potential for successful use.

A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes.

Generator of two successive shock waves focused to a common focal point has been developed. Two cylindrical pressure waves are generated by multichannel electrical discharges on separated electrodes with different diameters. Time delay between the discharges can be varied. Propagation of the waves has been studied by means of Schlieren photography and polyvinylidene fluoride (PVDF) shock gauges. Interaction of the shock waves takes place twice: inside the reflector volume and in the focal region. It was found that the mutual interaction of the waves inside the reflector volume (time delay up to 30 µs) influences propagation of the first wave, while propagation of the second wave is influenced at all time delays measured. Schlieren photos of the local region demonstrated that interaction of the two waves results in creation of a large number of secondary short wavelength shocks.

We have developed a generator of two successive shock waves focused to a common focal point. Amplitude of the pressure waves reaches up to 100 MPa at the focus and the rarefaction waves of 25 MPa in amplitude produce cavitations. Schlieren photography of the focal region has demonstrated that interaction of the two successive shocks results in creation of a very complex pressure field at the focus and in creation of many secondary spherical short wavelength shocks originated in collapsing cavitations. Measurements of waveforms by the PVDF shock gauges at the focus indicated that the second wave is strongly attenuated with the increasing time delay between the shocks. Suspension of the melanoma cells B16 has been exposed to 150 and 600 of focused shock waves. Afterwards the cells have been inoculated to the inbred mice C57B16. Volume of the tumors growing from the exposed cells has been compared for 50 days with the tumors growing from the non exposed cells. We have demonstrated that the exposure of the melanoma B16 cells to the focused shock waves results in a reduced growth rate of the tumors. The reduced growth rate has been observed in both the 150 and 600 shocks trials, however, for the case of 600 shocks it was much more pronounced

Abstract Streamer discharges in atmospheric gases are currently receiving increased attention in connection with environmental issues or new material treatment technologies. The chemical reactivity of streamer-produced plasma, created by various active atomic and molecular species, is a critical parameter for most application areas. Recently, advanced diagnostics based on optical and energy transfer methods have been applied to study dynamics and spatial distribution of several important streamer-produced species. This paper presents an overview of the most recently reported experimental achievements to monitor and detect reactive species, such as, e.g., NO, OH, and O3 radicals, nitrogen and oxygen atoms, or N2(A3Σ) metastables.