研究者詳細 - 石川　健治

論文 - 石川　健治

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Inhibition of glutamine metabolism increases sensitivity to plasma-activated medium-induced cytotoxicity 査読有り

Tanaka, S; Hayashi, S; Otsuka, T; Kamiya, T; Ishikawa, K; Hara, H

FREE RADICAL RESEARCH 58 巻 ( 3 ) 頁： 170 - 179 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Research

Non-thermal atmospheric pressure plasma (NTP), an ionized gas containing electrons, ions, radicals, and photons, has various biological effects, including wound healing and anticancer effects. Plasma-activated medium (PAM), which is prepared by irradiating medium with NTP, preferentially kills cancer cells. Large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) included in PAM are closely related to its anticancer effects. The precise mechanism of PAM-induced cytotoxicity is not fully understood; however, PAM exposure has been reported to reduce cellular energy metabolism. Glutamine (Gln) is an important amino acid as an energy source in cancer cells. Gln is converted to glutamate by glutaminase (GLS), and is utilized to synthesize ATP and glutathione (GSH). Expression levels of GLS have been shown to be higher in certain types of cancers. In this study, we examined the effects of GLS inhibition on PAM cytotoxicity using breast cancer MDA-MB-231 cells. Pretreatment with BPTES, a glutaminase 1 (GLS1) inhibitor, dose-dependently enhanced PAM-induced cell death. PAM-induced ROS production and γ-H2AX formation, a DNA damage marker, were increased in cells pretreated with BPTES compared with PAM alone. BPTES pretreatment enhanced a PAM-induced decrease in intracellular GSH, indicating the possibility that BPTES reduces the antioxidant capacity of MDA-MB-231 cells. In addition, BPTES pretreatment enhanced PAM-induced loss of the mitochondrial membrane potential and reduction of ATP production. Moreover, GLS1 knockdown promoted PAM-induced cell death. Taken together, the combination of GLS1 inhibitors such as BPTES is considered to be useful for enhancing the cytotoxic effects of PAM against cancer cells.

DOI： 10.1080/10715762.2024.2332343

Plasma-Driven Sciences: Exploring Complex Interactions at Plasma Boundaries 査読有り Open Access

Ishikawa, K; Koga, K; Ohno, N

PLASMA 7 巻 ( 1 ) 頁： 160 - 177 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plasma

Plasma-driven science is defined as the artificial control of physical plasma-driven phenomena based on complex interactions between nonequilibrium open systems. Recently, peculiar phenomena related to physical plasma have been discovered in plasma boundary regions, either naturally or artificially. Because laboratory plasma can be produced under nominal conditions around atmospheric pressure and room temperature, phenomena related to the interaction of plasma with liquid solutions and living organisms at the plasma boundaries are emerging. Currently, the relationships between these complex interactions should be solved using science-based data-driven approaches; these approaches require a reliable and comprehensive database of dynamic changes in the chemical networks of elementary reactions. Consequently, the elucidation of the mechanisms governing plasma-driven phenomena and the discovery of the latent actions behind these plasma-driven phenomena will be realized through plasma-driven science.

DOI： 10.3390/plasma7010011

Elaborate cooperation of poly(rC)-binding proteins 1/2 and glutathione in ferroptosis induced by plasma-activated Ringer's lactate 査読有り

Jiang, L; Zheng, H; Ishida, M; Lyu, Q; Akatsuka, S; Motooka, Y; Sato, K; Sekido, Y; Nakamura, K; Tanaka, H; Ishikawa, K; Kajiyama, H; Mizuno, M; Hori, M; Toyokuni, S

FREE RADICAL BIOLOGY AND MEDICINE 214 巻頁： 28 - 41 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Biology and Medicine

Reactive species are involved in various aspects of neoplastic diseases, including carcinogenesis, cancer-specific metabolism and therapeutics. Non-thermal plasma (NTP) can directly provide reactive species, by integrating atmospheric and interjacent molecules as substrates, to represent a handy strategy to load oxidative stress in situ. NTP causes apoptosis and/or ferroptosis specifically in cancer cells of various types. Plasma-activated Ringer's lactate (PAL) is another modality at the preclinical stage as cancer therapeutics, based on more stable reactive species. PAL specifically kills malignant mesothelioma (MM) cells, employing lysosomal ·NO as a switch from autophagy to ferroptosis. However, the entire molecular mechanisms have not been elucidated yet. Here we studied cytosolic iron regulations in MM and other cancer cells in response to PAL exposure. We discovered that cells with higher catalytic Fe(II) are more susceptible to PAL-induced ferroptosis. PAL caused a cytosolic catalytic Fe(II)-associated pathology through iron chaperones, poly (rC)-binding proteins (PCBP)1/2, inducing a disturbance in glutathione-regulated iron homeostasis. PCBP1/NCOA4-mediated ferritinophagy started at a later phase, further increasing cytosolic catalytic Fe(II), ending in ferroptosis. In contrast, PCBP2 after PAL exposure contributed to iron loading to mitochondria, leading to mitochondrial dysfunction. Therapeutic effect of PAL was successfully applied to an orthotopic MM xenograft model in mice. In conclusion, PAL can selectively sensitize MM cells to ferroptosis by remodeling cytoplasmic iron homeostasis, where glutathione and PCBPs play distinct roles, resulting in lethal ferritinophagy and mitochondrial dysfunction. Our findings indicate the clinical application of PAL as a ferroptosis-inducer and the potential of PCBPs as novel targets in cancer therapeutics.

DOI： 10.1016/j.freeradbiomed.2024.02.001

液中プラズマによるナノグラフェンの高速合成と機能化査読有り Open Access

近藤博基, 堤隆義, 石川健治, 堀勝, 平松美根男

表面と真空 67 巻 ( 2 ) 頁： 77 - 82 2024年2月

Surface sulfurization of amorphous carbon films in the chemistry of oxygen plasma added with SO2 or OCS for high-aspect-ratio etching 査読有り

Ishikawa, K; Nguyen, TTN; Aoki, Y; Sato, H; Kawakami, J; Tsuno, S; Hsiao, SN; Hori, M

APPLIED SURFACE SCIENCE 645 巻頁： 158876 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Applied Surface Science

Etching of oxygen-based plasmas with sulfur dioxide (SO<inf>2</inf>) or carbonyl sulfide (OCS) can form high-aspect-ratio (HAR) features of amorphous carbon films as carbon hard masks (CHM). The etched profiles showing shapes such as bowing or tapering are essentially dependent on the partial pressures of SO<inf>2</inf> or OCS in the O<inf>2</inf> plasma. The surface treated after the OCS-added plasma exhibited strong sulfurization by S<inf>2</inf> and CS species in S 2p of the X-ray photoelectron spectroscopy (XPS). The gas-phase interactions in the sulfur-oxygen-carbon system generated atoms and molecules, such as O, O<sup>+</sup>, and O<inf>2</inf><sup>+</sup>, which etched at the bottom and, conversely, SO, CO, CS, CS<inf>2</inf>, and S<inf>2</inf>, which inhibited isotropic etching at the sidewalls of the HAR features. The chemical reactions of the CS sulfurizing precursors in the gas phase were monitored by comparing their optical emission intensities at a wavelength of 257 nm with those of SO<inf>2</inf> at approximately 320 nm. The optimization of the HAR profiles of the CHM can be controlled by sidewall sulfurization of the CHM to obtain desirable profile shapes for the HAR features.

DOI： 10.1016/j.apsusc.2023.158876

Oxygen radical irradiation transforms an organic fertilizer L-tryptophan into an environment and human-friendly bactericide 査読有り

Iwata, N; Ishikawa, K; Nishikawa, Y; Kato, H; Shimizu, M; Kato, M; Tanaka, H; Ito, M; Hori, M

ENVIRONMENTAL TECHNOLOGY & INNOVATION 33 巻頁： 103496 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Environmental Technology and Innovation

Organic fertilizers are useful in hydroponic agriculture to bring about a sustainable society with minimal pollution. Irradiation of L-tryptophan (L-Trp) solutions with electrically neutral atomic oxygen produces immediate bactericidal activity. After oxygen radical irradiation of an L-Trp-containing Escherichia coli suspension at pH 6.3 for 5 min, a colony-forming unit assay showed a 6-log reduction in the number of surviving E. coli. Kynurenine and N’-formylkynurenine were identified as irradiation products in the solution using liquid chromatography–mass spectroscopy and nuclear magnetic resonance spectroscopy. Tryptophan radicals (Trp•) are precursors of kynurenine and N’-formylkynurenine and are detected using spin-trap electron spin resonance. The bactericidal effect is mediated by central carbon metabolism via enzyme deactivation in E. coli. Enzymatic deactivation via the oxygen radical irradiation of a solution containing the amino acid L-Trp eventually resulted in bacterial death.

DOI： 10.1016/j.eti.2023.103496

High linear energy transfer (LET) nature of alanine radical yield by soft X-ray irradiations studied by electron spin resonance (ESR) applications 査読有り

Nakagawa, S; Yokoya, A; Ohara, M; Usami, N; Asada, M; Fujiwara, M; Nakamura, T; Ishikawa, K

RADIATION PHYSICS AND CHEMISTRY 214 巻頁： 111304 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Radiation Physics and Chemistry

Radicals produced in alanine by irradiation of 2–7 keV X-rays were investigated by ESR applications; i.e., CW-ESR, pulse-ESR and ESR imaging. The relative radical yield decreased with the decreasing photon energy and the increasing dose. The 2D imaging showed that the radical concentration at the surface was extremely low even though the absorption of X-rays exponentially decreased with the penetration depth. The depth of the radical concentration peak was almost the same as the penetration depth for the X-ray irradiation with an energy lower than 5-keV. The product formed by radical recombination was observed by an LC/MS (liquid chromatograph-mass spectrum) analysis. For the soft X-ray irradiation, many radicals will be lost by the efficient radical-radical recombination due to the higher density of the radicals, similar to the high-LET irradiation by heavy ions. The spin-spin relaxation rate (1/T<inf>2</inf>), which correlates with the radical concentration, increased by the decreasing photon energy. The values of 1/T<inf>2</inf> for the soft X-rays were compatible to that for the heavy ions with the high-LET. Based on these observations, it is concluded that the effects of irradiation by soft X-rays are similar to high-LET irradiation.

DOI： 10.1016/j.radphyschem.2023.111304

Science and Applications of Plasma-Activated Solutions: Current Trends and Future Directions 査読有り国際共著

Tanaka H., Mizuno M., Ishikawa K., Miron C., Okazaki Y., Toyokuni S., Nakamura K., Kajiyama H., Ito M., Hori M.

Plasma Medicine 14 巻 ( 1 ) 頁： 67 - 76 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plasma Medicine

Recent research into plasma-activated solutions has unveiled their considerable potential across a range of applications, including cancer treatment, industrial processes, and environmental management. This review summarizes key findings from recent studies on the effects of plasma-activated solutions, focusing on their ability to induce cell death in glioblastoma cells, enhance ethanol production in yeast, and convert organic compounds into environmentally friendly substances. The review highlights the mechanisms by which plasma-activated solutions exert their effects, such as oxidative stress induction and cellular metabolic alterations. Addition-ally, it discusses the implications of these findings for overcoming challenges in cancer therapy, improving agricultural practices, and developing novel environmental technologies. The ongoing advancements in plasma technology offer promising avenues for future research and applications, underscoring its transformative potential in both scientific and practical domains.

DOI： 10.1615/PlasmaMed.v14.i1.50

Cold Atmospheric Pressure Plasma-Activated Liquids for Cancer Treatment 査読有り

Miron, C; Hiromasa, T; Britun, N; Hashizume, H; Ishikawa, K; Du, LY; Yamakawa, T; Kurebayashi, Y; Kondo, T; Kondo, H; Kajiyama, H; Toyokuni, S; Mizuno, M; Hori, M

ADVANCES IN DIGITAL HEALTH AND MEDICAL BIOENGINEERING, VOL 3, EHB-2023 111 巻頁： 150 - 162 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ifmbe Proceedings

Low-temperature plasma (LTP) is a promising tool that can assist in cancer treatment. Plasma-treated liquids have shown a selective cytotoxic effect on cancer cells attributed to reactive species formed in discharge, but this mechanism is not completely understood. In this study, the chemical compounds formed by plasma irradiation of Ringer’s lactate solutions and their effects on non-tumorigenic breast epithelial cells (MCF-10A) and breast cancer cells (MCF-7) were investigated. Among these compounds, glyceric acid increased the cell viability by more than two-fold compared to the control samples for MCF-10A and MCF-7 cells, whereas the tricarballylic acid had a pronounced cytotoxic effect on the cells when incubated with solutions of 0.6 mM to 50 mM concentrations. A good selectivity in killing the cancer cells was observed when the chemical compounds identified in plasma-treated liquids (such as ethyl acetate, glyceric acid, and tricarballylic acid) were used in a mixture solution of a certain concentration. The results show that the LTP-generated chemical compounds have both, stimulatory and inhibitory effects on cell viability, and the best selectivity is achieved only when these compounds are combined in a certain amount and have a synergistic effect, completely killing only the cancer cells.

DOI： 10.1007/978-3-031-62523-7_17

Bias-supply timing tailored to the aspect ratio dependence of silicon trench etching in Ar plasma with alternately injected C4F8 and SF6 査読有り Open Access

Yoshie, T; Ishikawa, K; Nguyen, TTN; Hsiao, SN; Tsutsumi, T; Sekine, M; Hori, M

APPLIED SURFACE SCIENCE 638 巻頁： 157981 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Applied Surface Science

In semiconductor device fabrication, the feature profiles of a high-aspect-ratio (HAR) Si trench is needed to be controlled considering aspect-ratio-dependent etching (ARDE). This is achieved by a cyclic process in which Ar plasma is sustained while C<inf>4</inf>F<inf>8</inf> and SF<inf>6</inf> are alternately injected and a short-period supply of a substrate bias is provided. Presently, the transient behaviors of gaseous and surface reactions are dynamically revealed by measuring the plasma parameters using a surface wave probe and optical emission spectroscopy. When the etched surface is fluorinated during the cycle, an ARDE-free Si-trench feature profile can be fabricated by controlling the bias-supply timing.

DOI： 10.1016/j.apsusc.2023.157981

An approach to reduce surface charging with cryogenic plasma etching using hydrogen-fluoride contained gases 査読有り

Hsiao S.N., Sekine M., Ishikawa K., Iijima Y., Ohya Y., Hori M.

Applied Physics Letters 123 巻 ( 21 ) 頁： 1 - 4 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Applied Physics Letters

The surface conductivity influences the etched pattern profiles in the plasma process. In the dielectric film etching, it is vital to reduce the charging build-up, which bends the trajectory of incoming ions for highly anisotropic etching. A significant increase in surface electric conductivity of SiO<inf>2</inf> films was observed when exposed to down-flow plasmas containing hydrogen fluoride (HF) at cryogenic temperature (−60 °C). This phenomenon can be attributed to two factors: (i) the absorption of HF and/or its compounds and (ii) the presence of H<inf>2</inf>O, which is likely originating from the etching by-product of SiO<inf>2</inf> and/or within the reactor. Comparing the surface electric resistance of the samples treated with HF plasmas to that of CF<inf>4</inf>/H<inf>2</inf> and C<inf>4</inf>F<inf>8</inf>/H<inf>2</inf> plasmas, we found that HF plasma treatment enables to be approximately three and six orders of magnitude lower. By using in situ x-ray photoemission spectroscopy, it was revealed that the presence of HF and/or its compounds and H<inf>2</inf>O were absorbed on the sample surface at −60 °C. These results strongly suggest that the cryogenic plasma etching with HF-contained gases can be used to alleviate the charge build-up issues.

DOI： 10.1063/5.0173553

Gas-phase study of the behavior of trimethyl gallium and triethyl gallium by optical emission spectroscopy and quadrupole mass spectroscopy for the growth of GaN by REMOCVD (radical-enhanced metalorganic chemical vapor deposition) 査読有り Open Access

Dhasiyan, AK; Jayaprasad, S; Amalraj, FW; Shimizu, N; Oda, O; Ishikawa, K; Hori, M

JAPANESE JOURNAL OF APPLIED PHYSICS 62 巻 ( SN ) 頁： SN1019 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Applied Physics

Metal-organic CVD (MOCVD) is a well-established means of epitaxial growth of III-nitrides in terms of production. To overcome the drawbacks of MOCVD, we have developed a radical-enhanced MOVCVD (REMOCVD) technique which is promising to grow group-III nitride materials at lower temperatures without ammonia gas. The gas phase behavior of trimethyl gallium (TMG) and triethyl gallium (TEG) in the chamber is studied with optical emission spectroscopy (OES) and quadrupole mass spectroscopy. From OES results, it is found that the parasitic reactions due to activated Ga and CN could be avoided by introducing hydrogen as a source gas together with nitrogen gas. The TEG is completely decomposed in REMOCVD at 550 °C which is a much lower temperature compared to TMG in a hydrogen atmosphere. Also, it is found that due to the low decomposition temperature of TEG, TEG contaminated the gas line which needs to be cleaned often.

DOI： 10.35848/1347-4065/acfd34

Deposition of carbon-based materials directly on copper foil and nickel foam as 2D-and 3D-networked metal substrates by in-liquid plasma 査読有り Open Access

Dela Vega, MSDC; Nguyen, TTN; Kondo, H; Tsutsumi, T; Ishikawa, K; Hori, M

PLASMA PROCESSES AND POLYMERS 20 巻 ( 11 ) 頁： 1 - 5 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plasma Processes and Polymers

In-liquid plasma (ILP) process has been an attractive route for nanomaterial synthesis due to its high-yield production in low-temperature atmospheric pressure conditions. In comparison with conventional ILP synthesis that produces free-standing nanomaterials, this work brings a new perspective on the application of the ILP process through carbon formation directly on ethanol-immersed two-dimensional (foil) and three-dimensional (3D) (foam) metal substrates. Three types of carbon, including graphene, graphitic carbon, and amorphous carbon, were simultaneously produced during plasma discharge. Graphitic and amorphous carbon formed radially and coexisted on the metal substrate surface, while free-standing graphene was produced in ethanol. A conformal coating was achieved on the exterior surface of the 3D-networked substrate. The proposed mechanism for carbon formation on metal substrates is presented here.

DOI： 10.1002/ppap.202300036

低温プラズマおよびハイパーサーミア併用効果を用いたがん治療の可能性招待有り査読有り Open Access

近藤隆, 橋爪博司, 田中宏昌, 石川健治, 齋藤淳一, 堀勝

Thermal Medicine 39 巻 ( 3 ) 頁： 21 - 30 2023年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：日本ハイパーサーミア学会

<p>　プラズマは固体・液体・気体に続く物質の第4の状態である．狭義のプラズマは，気体を構成する分子が電離し，陽イオンと電子に分かれて運動している状態であり，電離気体に相当する．いわゆる熱プラズマはすでに消化管や鼻腔表面の組織凝固壊死を誘導する熱凝固装置治療に使われている．近年，低温プラズマ技術の発展が目覚ましく，止血，がん治療，遺伝子・薬物導入，殺菌・滅菌，創傷治療等，多くの医療分野への利用が注目されている．低温大気圧プラズマは水溶液中には多量の活性種を生成する．但し，直接照射の場合の課題はその深達性にある．そこで，我々はハイパーサーミアの併用により大気圧プラズマ誘発活性種がより多く細胞内に導入されることを期待してアポトーシスを指標にその増強効果を検討した．</p><p>　実験にはヒトリンパ腫細胞株であるU937細胞を用いた．プラズマにはHeプラズマを用いた．その結果，単独では細胞致死効果を示さない42 ℃の温熱処理を付加することでプラズマ併用により相乗的なアポトーシスの増強効果が得られた．同時に細胞内活性酸素種も増加した．単独では致死効果が十分でない場合でもハイパーサーミアを付加することで細胞内への活性酸素種の導入が増え，致死効果の増強に寄与したものと思われる．</p><p>　最近，プラズマ照射された溶液の生物作用が注目されている．プラズマ活性培養液やプラズマ活性乳酸リンゲル液のがん細胞致死効果が注目されている．これらプラズマ活性化溶液と温熱処理は細胞内に酸化ストレス誘導をすることが知られており，ハイパーサーミアとの併用による相乗効果が期待される．本稿ではプラズマを用いたがん治療の現状について解説するともにハイパーサーミア併用の有用性について言及する．</p>

DOI： 10.3191/thermalmed.39.21

Development of an experimental system for cell viability assays of yeasts using gas-temperature controllable plasma jets 査読有り Open Access

Yoshimura, S; Otsubo, Y; Yamashita, A; Johzuka, K; Tsutsumi, T; Ishikawa, K; Hori, M

JAPANESE JOURNAL OF APPLIED PHYSICS 62 巻 ( SL ) 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Applied Physics

The characteristics of a gas-temperature-controllable atmospheric-pressure helium plasma jet and the development of an experimental system for cell viability assays of yeasts (fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae) are reported. The physicochemical properties of the plasma plume, which can maintain the temperature of the irradiated object at a temperature suitable for yeast, were not significantly different from those of a typical helium plasma jet. Furthermore, good reproducibility of cell viability was observed when gas temperature, gas flow rate, applied high voltage, and irradiation distance remained fixed, and only irradiation time was used as a parameter. This experimental system allows us to carry out various experiments, such as the search for plasma-resistant mutants that will contribute to the identification of genes involved in resistance to direct plasma irradiation.

DOI： 10.35848/1347-4065/acd4ca

Organic decomposition and synthesis reactions in lactated solution exposed to nonequilibrium atmospheric pressure plasma 査読有り Open Access

Liu, Y; Ishikawa, K; Tanaka, H; Miron, C; Kondo, T; Nakamura, K; Mizuno, M; Kajiyama, H; Toyokuni, S; Hori, M

PLASMA PROCESSES AND POLYMERS 20 巻 ( 5 ) 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plasma Processes and Polymers

Lactate is used in the food and pharmaceutical industries and is a crucial intermediate for synthesis. Plasma-activated lactate (PAL) in Ringer's solution was recently shown to have effective antitumor action. Small molecule aldehydes, ketones, and organic acids were produced from lactate during plasma exposure, and five<sup>-</sup>membered conjugated lactone isomers of furanone (C<inf>5</inf>H<inf>6</inf>O<inf>2</inf>) were detected formed by interactions of lactate or its fragments with •OH, organic radicals, and H<inf>2</inf>O<inf>2</inf>. 2,3-Dimethyl-tartaric acid may be the effective component in PAL for the selective killing of cancer but not normal cells and possible pathways for its synthesis are provided. Aqueous reaction mechanisms are explained, including dehydration, esterification, hydrolysis, and dimerization. This study will help develop novel cancer therapies and further plasma organic chemistry.

DOI： 10.1002/ppap.202200193

Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device 査読有り Open Access

Onoshima, D; Hase, T; Kihara, N; Kuboyama, D; Tanaka, H; Ozawa, N; Yukawa, H; Sato, M; Ishikawa, K; Hasegawa, Y; Ishii, M; Hori, M; Baba, Y

ACS MEASUREMENT SCIENCE AU 3 巻 ( 2 ) 頁： 113 - 119 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACS Measurement Science Au

Considering the challenges in isolating circulating tumor cells (CTCs) pertaining to cellular stress and purity, we report the application of a blood microfiltration device as an optimal approach for noninvasive liquid biopsy to target CTCs. We experimentally analyzed the filtration behavior of the microfilter using pressure sensing to separate tumor cells from leukocytes in whole blood. This approach achieved an average recovery of >96% of the spiked tumor cells and depletion of >99% of total leukocytes. Furthermore, we carried out genomic profiling of the CTCs using the blood microfiltration device. The method was also applied in a clinical setting; DNA amplification was performed using a small number of microfiltered CTCs and epidermal growth factor receptor mutations were successfully detected to characterize the efficacy of molecularly targeted drugs against lung cancer. Overall, the proposed method can provide a tool for evaluating efficient filtration pressure to concentrate CTCs from whole blood.

DOI： 10.1021/acsmeasuresciau.2c00057

Manipulation of etch selectivity of silicon nitride over silicon dioxide to a-carbon by controlling substate temperature with a CF4/H2 plasma 査読有り

Hsiao, SN; Britun, N; Nguyen, TTN; Tsutsumi, T; Ishikawa, K; Sekine, M; Hori, M

VACUUM 210 巻頁： 111863 - 111863 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Vacuum

The effects of substrate temperature (T<inf>s</inf>) on the etch rate (ER) of the PECVD-prepared SiN, SiO<inf>2</inf> and amorphous carbon (a-C) films, and their selectivity were investigated with a CF<inf>4</inf>/H<inf>2</inf> plasma. The ERs for the SiN at all T<inf>s</inf> were higher than that for the SiO<inf>2</inf> films. As T<inf>s</inf> was decreased from 50 to −20 °C, the ER for the SiN decreased. Contrarily, the ER of the SiO<inf>2</inf> films increased. The etching selectivity of SiN over SiO<inf>2</inf> reached to near unity when the T<inf>s</inf> was −20 °C. At the same time, the ER of for the a-C films was found to be around 0.1 nm/s and irrespective of T<inf>s</inf>. The fluorocarbon (FC) thickness was greater for the SiO<inf>2</inf> films than that of the SiN. The lower ER for the SiO<inf>2</inf> was therefore attributed to the thicker FC layer and resultant etching mechanism. As the T<inf>s</inf> was decreased, the FC thickness on the SiO<inf>2</inf> films decreased, which led to the ER decrease. The decrease of ER for the SiN etching at the low temperature was likely due to the higher stability of the surface N–H modification layer, compared with that processed at 20 °C, which was confirmed by the in situ FTIR.

DOI： 10.1016/j.vacuum.2023.111863

High-performance glass filters for capturing and culturing circulating tumor cells and cancer-associated fibroblasts 査読有り Open Access

Tanaka, H; Iwata, D; Shibata, Y; Hase, T; Onoshima, D; Yogo, N; Shibata, H; Sato, M; Ishikawa, K; Nagasawa, I; Hasegawa, Y; Ishii, M; Baba, Y; Hori, M

SCIENTIFIC REPORTS 13 巻 ( 1 ) 頁： 4130 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.

DOI： 10.1038/s41598-023-31265-9

Generation and measurement of low-temperature plasma for cancer therapy: a historical review 査読有り Open Access

Ishikawa, K; Takeda, K; Yoshimura, S; Kondo, T; Tanaka, H; Toyokuni, S; Nakamura, K; Kajiyama, H; Mizuno, M; Hori, M

FREE RADICAL RESEARCH 57 巻 ( 3 ) 頁： 239 - 270 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Research

This review provides a description of the historical background of the development of biological applications of low-temperature plasmas. The generation of plasma, methods and devices, plasma sources, and measurements of plasma properties, such as electron dynamics and chemical species generation in both gaseous and aqueous phases, were assessed. Currently, direct irradiation methods for plasma discharges contacting biological surfaces, such as the skin and teeth, are related to plasma biological interactions. Indirect methods using plasma-treated liquids are based on plasma–liquid interactions. The use of these two methods is rapidly increasing in preclinical studies and cancer therapy. The authors address the prospects for further developments in cancer therapeutic applications by understanding the interactions between the plasma and living organisms.

DOI： 10.1080/10715762.2023.2230351

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