Sang Sik Yang

Atmospheric-Pressure Plasma Jet Induces Apoptosis Involving Mitochondria via Generation of Free Radicals

The plasma jet has been proposed as a novel therapeutic method for anticancer treatment. However, its biological effects and mechanism of action remain elusive. Here, we investigated its cell death effects and underlying molecular mechanisms, using air and N2 plasma jets from a micro nozzle array. Treatment with air or N2 plasma jets caused apoptotic death in human cervical cancer HeLa cells, simultaneously with depolarization of mitochondrial membrane potential. In addition, the plasma jets were able to generate reactive oxygen species (ROS), which function as surrogate apoptotic signals by targeting the mitochondrial membrane potential. Antioxidants or caspase inhibitors ameliorated the apoptotic cell death induced by the air and N2 plasma jets, suggesting that the plasma jet may generate ROS as a proapoptotic cue, thus initiating mitochondria-mediated apoptosis. Taken together, our data suggest the potential employment of plasma jets as a novel therapy for cancer.

Fabrication and test of a thermopneumatic micropump with a corrugated p + diaphragm

Abstract This paper presents a thermopneumatic micropump fabricated by micromachining. The micropump consists of a p + silicon diaphragm, a micro heater and a pair of nozzle/diffuser. The thermopneumatic actuator of this paper is characterized by a corrugated diaphragm, which is more flexible than a flat one. The diaphragm is driven by the air cavity pressure variation caused by the ohmic heating and the natural cooling. If the diaphragm of the micropump vibrates, the fluid flows in one direction through a nozzle/diffuser. The experimental result illustrates that the deflection of the corrugated diaphragm is about three times that of the flat one. The maximum flow rate of the micropump with the corrugated diaphragm is about 14 μl/min at 4 Hz when the input voltage and duty ratio are 8 V and 40%, respectively.

A phase-change type micropump with aluminum flap valves

In this paper, a phase-change type micropump is presented. This micropump consists of a pair of aluminum flap valves and a phase-change type actuator. The actuator is composed of a heater, a silicone rubber diaphragm and a working fluid chamber. The diaphragm is actuated by the vaporization and the condensation of the working fluid. The micropump is fabricated by the anisotropic etching, the boron diffusion and the metal evaporation. The dimension of the micropump is 8.5 mm × 5 mm × 1.7 mm. The forward and the backward flow characteristics of the flap valve illustrate the appropriateness as a check valve. The flow rate of the micropump is measured for various voltages, frequencies and duty cycles of the square-wave input. When the square-wave input voltage of 10 V is applied to the heater, the maximum flow rate of the micropump is 6.1 μl min−1 at 0.5 Hz and the duty ratio of 60% for zero pressure difference. The maximum backward pressure when the flow rate is zero is 10 mm H2O.

Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma.

The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH−, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells.

Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy

We propose a plasma-jet device with a micrometer-sized nozzle array for use in a cancer therapy. Also, we show the biological effects of atmospheric-pressure plasma on living cells. Nitrogen-plasma activated a surrogate DNA damage signal transduction pathway, called the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 pathway, suggesting that the nitrogen-plasma generates DNA double-strand breaks. Phosphorylation of H2AX and p53 was detected in the plasma-treated cells, leading to apoptotic cell death. Thus, an effect for the nitrogen plasma in the control of apoptotic cell death provides insight into the how biological effects of the nitrogen-plasma can be applied to the control of cell survival, a finding with potential therapeutic implications.

Fabrication of a novel micro time-of-flight mass spectrometer

This paper presents the fabrication and the tests of a novel micro-mass spectrometer fabricated by micro-machining and emission test of hot electron for ionization. A micro-mass spectrometer consists of a micro-ion source and a micro-ion separator. The micro-ion source consists of a hot filament and grid electrodes. Electrons emitted from a hot filament are to ionize some sample molecules. The ions are accelerated to an ion detector by an electric field of the ion separator. Mass can be analyzed by using the time-of-fight depending on the mass-to-charge ratio. The current of hot electron emission from the hot filament is measured for various input voltages and the ion separation is tested for acetone.

A micro rate gyroscope based on the SAW gyroscopic effect

We propose a micro rate gyroscope (MRG) based on the surface acoustic wave (SAW) gyroscopic effect for extremely high-shock military applications. We not only derived theoretically the SAW gyroscopic gain factor in a ST-cut quartz by introducing a wave velocity ratio and the perturbation method, but also verified this gain factor by experiment. The proposed SAWMRG, which consists of two delay-line oscillators, operates as a differential scheme. To estimate an inherent insertion loss, we adopted the equivalent circuit model in the design process of the delay line. The 9 × 9 mm2 SAWMRG was fabricated on a ST-cut quartz and loaded into a specially designed low temperature co-fired ceramic (LTCC) package to ensure good RF characteristics. The center frequency and the insertion loss of the delay line are measured at 98.6 MHz and 15.2 dB, respectively. We evaluated the performance of the SAWMRG, using a rate table and stochastic noise analysis, revealing a sensitivity of 0.431 Hz deg−1 s−1 in the angular rates up to 2000 deg s−1 and a white noise of 0.55 deg s−1 Hz−1/2, respectively. Consequently the feasibility of the proposed SAWMRG was verified through a set of performance evaluations, confirming the theoretical predictions.

Non-Thermal Atmospheric Pressure Plasma Inhibits Thyroid Papillary Cancer Cell Invasion via Cytoskeletal Modulation, Altered MMP-2/-9/uPA Activity

Plasma, the fourth state of matter, is defined as a partially or completely ionized gas that includes a mixture of electrons and ions. Advances in plasma physics have made it possible to use non-thermal atmospheric pressure plasma (NTP) in cancer research. However, previous studies have focused mainly on apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In this study, we investigated the effect of NTP on invasion or metastasis, as well as the mechanism by which plasma induces anti-migration and anti-invasion properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1). Wound healing, pull-down, and Transwell assays demonstrated that NTP reduced cell migration and invasion. In addition, NTP induced morphological changes and cytoskeletal rearrangements, as detected by scanning electron microscopy and immunocytochemistry. We also examined matrix metalloproteinase (MMP)-2/-9 and urokinase-type plasminogen activator (uPA) activity using gelatin zymography, uPA assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA activities and rearranging the cytoskeleton, which is regulated by the FAK/Src complex. These findings suggest novel actions for NTP and may aid in the development of new therapeutic strategies for locally invasive and metastatic cancers.

Non-thermal atmospheric pressure plasma induces apoptosis in oral cavity squamous cell carcinoma: Involvement of DNA-damage-triggering sub-G1 arrest via the ATM/p53 pathway

Recent advances in physics have made possible the use of non-thermal atmospheric pressure plasma (NTP) in cancer research. Although increasing evidence suggests that NTP induces death of various cancer cell types, thus offering a promising alternative treatment, the mechanism of its therapeutic effect is little understood. In this study, we report for the first time that NTP led to apoptotic cell death in oral cavity squamous cell carcinoma (OSCC). Interestingly, NTP induced a sub-G(1) arrest in p53 wild-type OSCCs, but not in p53-mutated OSCCs. In addition, NTP increased the expression levels of ATM, p53 (Ser 15, 20 and 46), p21, and cyclin D1. A comet assay, Western blotting and immunocytochemistry of γH2AX suggested that NTP-induced apoptosis and sub-G(1) arrest were associated with DNA damage and the ATM/p53 signaling pathway in SCC25 cells. Moreover, ATM knockdown using siRNA attenuated the effect of NTP on cell death, sub-G(1) arrest and related signals. Taken together, these results indicate that NTP induced apoptotic cell death in p53 wild-type OSCCs through a novel mechanism involving DNA damage and triggering of sub-G(1) arrest via the ATM/p53 pathway. These findings show the therapeutic potential of NTP in OSCC.

Fabrication of a thermopneumatic microactuator with a corrugated p+ silicon diaphragm

Abstract This paper presents a thermopneumatic microactuator consisting of a p+ silicon diaphragm and a micro heater which are fabricated by micromaching. The thermopneumatic actuator of this paper is characterized by a corrugated diaphragm, which is more flexible than a flat one. The diaphragm is driven by the air cavity pressure variation caused by ohmic heating and natural cooling. The diaphragm deflection is measured with a laser displacement meter. The static load-deflection characteristics of the corrugated and the flat diaphragms to pneumatic pressure are obtained from experiments and compared with the calculated results. Also, the dynamic characteristics of the thermopneumatic actuators are investigated experimentally. The steady-state deflection of the actuator diaphragm is proportional to the voltage applied to the heater, and the mechanical sensitivity of the corrugated diaphragm and the flat one are 6.25 and 2.22 μm/V, respectively. The experimental result illustrates that the microactuator with the corrugated diaphragm is better than that with the flat one with respect to the performance.