S13-2
Physico-chemical research of the interaction
between gaseous plasma and living organism
プラズマ生体相互作用の物理化学研究
Katsuhisa Kitano 1, Satoshi Ikawa 2, Yoichi Nakashima 2, Atsushi Tani 3
北野勝久 1,井川聡 2,中島陽一 2,谷篤史 3
1

Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
Technology Research Institute of Osaka Prefecture
2-7-1 Ayumino, Izumi, Osaka 594-1157, Japan3
Department of Earth and Space Science, Graduate School of Science, Osaka University
1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan１大阪大学工学研究科 アトミックデザイン研究センター 〒565-0871 大阪府吹田市山田丘2-1、２
大阪府立産業技術総合研究所、３大阪大学理学研究科
Many types of applications to plasma medicine have been tried. The combination with plasma science andmedical science belongs to interdisciplinary science, and more attentions should be done tocross-disciplinary study between them. Plasma generates active species in gas and liquid phases, and they
react with biomacromolecules of living organism, and some desirable effect would be finally obtained.
Plasma is not an instrument of magic. For beneficial use of plasma, it is important to find applications
which cannot be achieved by other methods (commercially available chemicals, UV lamp, etc.). In thispaper, expected elementary reactions are discussed step by step.

1. Plasma induced chemical reactions for plasma
medicine
Based on unique characteristics of atmosphericpressure plasmas, novel plasma applications tohuman body 'Plasma Medicine' have attractedattention. Considering wet conditions of bodysystems, the concept of plasma process in a liquid
phase is essential. Various types of active species(ions, electrons, neutrals, radicals, UV, and so on)
generated in plasma (gas phase) can be used forsome chemical reactions in a liquid phase. For that
purpose, atmospheric pressure plasmas with room
temperature are suitable (Fig. 1) to avoid thermal
damages to human body. Of course, instead ofplasma itself some chemical species can penetrate
into the liquid to induce some chemical reactions.
In other words, plasma is a sort of tool for
producing reactive species. Although many

Fig. 1 Plasma jet exhausted to a finger withoutburning.

applications in plasma medicine have been
proposed, such a plasma-induced reactive species isknown to be toxic to living organism in general.
Our research target is the disinfection of human
body, achieving beneficial use of these activespecies. We have developed the reduced pH method,where strong bactericidal activity can be achieved if
the solution is sufficiently acidic [1]. This method
has been confirmed to be effective to sterilize
human extracted tooth as caries infected model [2].
In this paper, the interactions between gaseous
plasma and living organism are discussed in turnbased on physico-chemical approach, by taking thetheme of the reduced pH method.
2. Effective sterilization by the reduced pHmethod
For the plasma disinfection in the body fluid, wehave successfully developed the reduced pH
method that strong bactericidal activity can beachieved when the solution is sufficiently acidic. It
is considered that strong bactericidal activity isbrought by hydroperoxy radical (HOO•) generated
from the association of hydrogen ion (H+) andsuperoxide anion radical (O2–•). The critical pH
value is associated with pKa of the dissociation
equilibrium between these radicals, which is knownto be approximately 4.8. This means that O2–• canbe changed into HOO•, which have much stronger
bactericidal activity, in lower pH [3].

3. Active species in gas and liquid phases
Atmospheric plasmas generate ROS (reactiveoxygen species) and RNS (reactive nitrogenspecies) by contacting and/or mixing source gas(e.g. air, oxygen, and nitrogen). These activespecies exist not only inside plasma plume but
outside. Some ions with hydrated cluster can exist
apart from plasma source, which sometimes called
as air ions. Spatial distributions of each species aredependent on chemical reaction, charge transfer andso on. Many types of negative and positive ionswere analyzed by atmospheric MS (massspectrometer) with 3-stage differential pumping.
Species in a gas phase can be transferred into aliquid phase beyond the gas-liquid interface.
Chemical reactions occur in the liquid andpenetration depth depends on primary reactions.
Numerical simulation of assumed chemical
reactions in the liquid was done using ourexperimental results. In short, species with shorthalf-life hardly diffuse into the liquid. ESR(electron spin resonance) measurements was used
to measure O2-•, OH•, 1O2, and H• [4]. IC (ionchromatography) was to nitrate (NO3-) and nitrite
ions (NO2-). Ozone (O3) and hydrogen peroxide(H2O2) was done by another method. For scientificdiscussion on complex and extreme reaction fields
induced by plasmas, positive and negative control
experiments were done.
4. Biochemical reactions of biomacromolecule
Active species in the liquid react withbiomacromolecule ( protein, polysaccharide, lipid,nucleic acid) of living organism as elementary
reaction, and macro effect (propagation, aging,apoptosis, necrosis, sterilization and so on) would
be brought in consequence. To understand thischemical reaction process, the solutions ofbiomacromolecules were treated by plasma andanalyzed by MALDI-TOFMS, CD (circulardichroism) spectroscopy, quantitative PCR, enzyme
assay and so on [5-7]. Key point is that chemicallymodified biomacromolecules should be analyzed
from the view point of 'function'. For instance,
FT-IR and XPS measurements of chemical binding
have little information against such macromolecules.
This is a fundamental step for elucidating chemical
reactions by plasma for biomedical applications.
5. Molecular biological approach
Although many types of molecular reactions arebrought to living organism at the same time, key
reaction (factor) to contribute should be identified
using molecular biological method. Usually, one
affect is brought by one reaction with otherirrelative reactions. By the reduced pH method,bacteria are not simply killed but proliferation
activity is inactivated with some physiologicalactivity. This resembles UV sterilization, but noeffective damage of DNA is observed.
6. How to supply active species
For the purpose of supplying chemical species,
indirect plasma exposure can be used besides direct
plasma exposure. It is not necessary that plasma andliquid (human body) are in contact. Remote(afterglow) plasma can be used for some
application like ozone therapy. The plasma treatedwater (PTW) with strong bactericidal activity canbe used by cryopreservation. Key concept isselective supply of active species with many typesof supplying methods. To minimize undesirable
side effects, non-related species should not besupplied. To maximize the desired effect, related
species should be supplied selectively withadequate quantity.
7. Plasma medical applications as science
Although many types of applications to medicine
have been proposed and tried, experimental
researches have been done with theoretical research
postponed. For scientific research, reactions should
be understood step by step.
Acknowledgments
This study was supported by KAKENHI
Grant-in-Aid for Scientific Research B (23340176)
and Innovative Areas "Plasma Medical Innovation"(25108505), A-STEP (AS2124901F) from JST andthe national cancer center research and development
fund (23-A-15).
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