Plasma medicine
Encyclopedia
Plasma medicine is an innovative and emerging field combining plasma physics
, life sciences
and clinical medicine
to use physical plasma for therapeutic applications
. Initial experiments confirm that plasma can be effective in in vivo
antiseptic
s without affecting surrounding tissue
and, moreover, stimulating tissue regeneration. Based on sophisticated basic research on plasma-tissue interaction, first therapeutic applications in wound
healing, dermatology
and dentistry
will be opened.
Plasma, described as the fourth state of matter, comprises charged species, active molecules and atoms and is also a source of UV-photons. These plasma-generated active species are useful for several bio-medical applications such as sterilization of implant
s and surgical instruments. Sensitive applications of plasma, like subjecting human body or internal organs to plasma treatment for medical purposes, are also possible. This possibility is profoundly being investigated by research groups worldwide under the highly-interdisciplinary research field called 'plasma medicine'.
into medicine years ago.
Plasma medicine can be subdivided into three main fields:
can be used, for direct therapeutic applications only atmospheric pressure plasma source
s are applicable.
One such plasma source that can be applied on human body is based on the dielectric barrier discharge
(DBD) principle. A conventional DBD device comprises two planar electrodes with at least one of them covered with a dielectric material and the electrodes are separated by a small gap which is called the discharge gap. However, for medical application of DBD devices, the human body itself can serve as one of the two electrodes making it sufficient to devise plasma sources that comprise of only one electrode covered with a dielectric
such as alumina or quartz
. DBD for medical applications such as for treatment of skin diseases and wounds, tumor treatment and disinfection of skin surface are currently under investigation.
The high reactivity of plasma is a result of different plasma components: electromagnetic radiation
(UV/VUV
, visible light, IR
, high-frequency electromagnetic fields, etc.) on the one hand and ion
s, electron
s and reactive chemical species, primarily radicals
, on the other. Besides surgical plasma application like argon plasma coagulation
(APC), which is based on high-intensity lethal plasma effects, first and sporadic non-thermal therapeutic plasma applications are documented in literature. However, the basic understanding of mechanisms of plasma effects on different components of living systems is in the early beginning.
Especially for the field of direct therapeutic plasma application, a fundamental knowledge of the mechanisms of plasma interaction with living cells
and tissue is essential as a scientific basis.
or to qualify polymer surfaces
for cell culturing
and tissue engineering
. Plasma-based methods and processes for sterilization, decontamination or reprocessing of medical and diagnostic devices, pharmaceutical products or packaging materials are under development worldwide. Both fields are more or less indirect medical plasma applications.
plasma activity, current research in plasma medicine is mainly focussed on the following fields:
Combination of plasma technology and plasma diagnostics
with cell biological
, biochemical and chemical analytical techniques
based on in vitro models using microorganism
s as well as cell and tissue cultures, will facilitate a sophisticated evaluation of biological plasma effects.
To achieve sustained success of plasma medicine, for any potential therapeutic application optimal plasma composition (radicals, irradiation, temperature, etc.), useful application rate and acceptable relation between desired therapeutic effects and adverse reactions
have to be found. This can be realized only in close collaboration between plasma physicists, life scientists and clinical physicians.
M. Moisan, J. Barbeau, S. Moreau, J. Pelletier, M. Tabrizian, and L’H. Yahia, “ Low Temperature Sterilization Using Gas Plasmas: A Review of the Experiments, and an Analysis of the Inactivation Mechanisms”, Int. J. Pharmaceutics, Vol. 226, pp. 1–21, 2001.
M. Laroussi, A. Fridman, and R. M. Satava, “Plasma Medicine”, Plasma Processes and Polymers, Vol. 5, No. 6, 2008.
M. Laroussi, “ Non-Thermal Decontamination of Biological Media by Atmospheric Pressure Plasmas: Review, Analysis, and Prospects”, IEEE Trans. Plasma Sci., Vol. 30, No. 4, pp. 1409–1415, 2002 .
I.E. Kieft, M. Kurdi, and E. Stoffels, “Reattachment and Apoptosis after Plasma-Needle Treatment of Cultured Cells”, IEEE Trans. Plasma Sci., Vol. 34, No.4, pp. 1331–1336, 2006.
M. Laroussi, D. A. Mendis, and M. Rosenberg, “Plasma Interaction with Microbes”, New Journal of Physics, Vol. 5, pp. 41.1-41.10, 2003.
M. G. Kong, G. Kroesen, G. Morfill, T. Nosenko, T. Shimizu, J. van Dijk and J. L. Zimmermann, “Plasma Medicine: An Introductory Review”, New J. Physics, Vol. 11, 115012, 2009.
M. Laroussi, “Low Temperature Plasmas for Medicine?”, IEEE Trans. Plasma Sci., Vol. 37, No. 6, pp. 714–725, 2009.
Atmospheric-pressure plasma sources: Prospect tools for plasma medicine, K.-D. Weltmann, E. Kindel, T. von Woedtke, M. Hähnel, M. Stieber and R. Brandenburg, Pure Appl. Chem. 82 (2010) 1223–1237
Atmospheric Pressure Plasma Jet for Medical Therapy: Plasma Parameters and Risk Estimation, K.-D. Weltmann, E. Kindel, R. Brandenburg, C. Meyer, R. Bussiahn, C. Wilke and T. von Woedtke, Contrib. Plasma Phys. 49 (2009) 631–640
Antimicrobial treatment of heat sensitive products by miniaturized atmospheric pressure plasma jets (APPJs), K.-D. Weltmann, R. Brandenburg, T. von Woedtke, J. Ehlbeck, R. Foest, M. Stieber and E. Kindel, J. Phys. D: Appl. Phys. 41 (2008) 194008
Plasma (physics)
In physics and chemistry, plasma is a state of matter similar to gas in which a certain portion of the particles are ionized. Heating a gas may ionize its molecules or atoms , thus turning it into a plasma, which contains charged particles: positive ions and negative electrons or ions...
, life sciences
Life sciences
The life sciences comprise the fields of science that involve the scientific study of living organisms, like plants, animals, and human beings. While biology remains the centerpiece of the life sciences, technological advances in molecular biology and biotechnology have led to a burgeoning of...
and clinical medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
to use physical plasma for therapeutic applications
Therapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
. Initial experiments confirm that plasma can be effective in in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
antiseptic
Antiseptic
Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...
s without affecting surrounding tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
and, moreover, stimulating tissue regeneration. Based on sophisticated basic research on plasma-tissue interaction, first therapeutic applications in wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
healing, dermatology
Dermatology
Dermatology is the branch of medicine dealing with the skin and its diseases, a unique specialty with both medical and surgical aspects. A dermatologist takes care of diseases, in the widest sense, and some cosmetic problems of the skin, scalp, hair, and nails....
and dentistry
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
will be opened.
Plasma, described as the fourth state of matter, comprises charged species, active molecules and atoms and is also a source of UV-photons. These plasma-generated active species are useful for several bio-medical applications such as sterilization of implant
Implant (medicine)
An implant is a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. Medical implants are man-made devices, in contrast to a transplant, which is a transplanted biomedical tissue...
s and surgical instruments. Sensitive applications of plasma, like subjecting human body or internal organs to plasma treatment for medical purposes, are also possible. This possibility is profoundly being investigated by research groups worldwide under the highly-interdisciplinary research field called 'plasma medicine'.
Research fields
Progress in life sciences is increasingly caused by utilization of unrelated technologies and knowledge. In this spirit, microelectronics, optics, material sciences or nanotechnology became key technologies in modern medicine. A similar trend is expected now concerning plasma technology. Actually, plasma medicine is emerging worldwide as an independent medical field - comparable to the launch of laser technologyLaser medicine
Laser medicine is the use of various types of lasers in medical diagnosis, treatment, or therapy. Types of lasers used in medicine include in principle any laser design, especially:* CO2 lasers* diode lasers* dye lasers* excimer lasers* fiber lasers...
into medicine years ago.
Plasma medicine can be subdivided into three main fields:
- Non-thermal atmospheric-pressure direct plasma for medical therapy
- Plasma-assisted modification of bio-relevant surfacesBiocompatibilityBiocompatibility is related to the behavior of biomaterials in various contexts. The term may refer to specific properties of a material without specifying where or how the material is used , or to more empirical clinical success of a whole device in...
- Plasma-based bio-decontamination and sterilizationSterilization (microbiology)Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents present on a surface, contained in a fluid, in medication, or in a compound such as biological culture media...
Non-thermal atmospheric-pressure plasma for medical therapy
Recently, one of challenges is the application of non-thermal plasmas directly on the surface of human body or on internal organs. Whereas for surface modification and biological decontamination both low-pressure and atmospheric pressure plasmasAtmospheric-pressure plasma
Atmospheric-pressure plasma is the name given to the special case of a plasma in which the pressure approximately matches that of the surrounding atmosphere – the so-called normal pressure....
can be used, for direct therapeutic applications only atmospheric pressure plasma source
Plasma source
Plasma sources generate plasmas.Excitation of a plasma requires partial ionization of neutral atoms and/or molecules of a medium.There are several ways to cause ionization:collisions of energetic particles, strong electric fields acting on bond...
s are applicable.
One such plasma source that can be applied on human body is based on the dielectric barrier discharge
Dielectric barrier discharge
Dielectric-barrier discharge is the electrical discharge between two electrodes separated by an insulating dielectric barrier. Originally called silent discharge and also known as ozone production discharge or partial discharge, it was first reported by Ernst Werner von Siemens in 1857.- Process...
(DBD) principle. A conventional DBD device comprises two planar electrodes with at least one of them covered with a dielectric material and the electrodes are separated by a small gap which is called the discharge gap. However, for medical application of DBD devices, the human body itself can serve as one of the two electrodes making it sufficient to devise plasma sources that comprise of only one electrode covered with a dielectric
Dielectric
A dielectric is an electrical insulator that can be polarized by an applied electric field. When a dielectric is placed in an electric field, electric charges do not flow through the material, as in a conductor, but only slightly shift from their average equilibrium positions causing dielectric...
such as alumina or quartz
Quartz
Quartz is the second-most-abundant mineral in the Earth's continental crust, after feldspar. It is made up of a continuous framework of SiO4 silicon–oxygen tetrahedra, with each oxygen being shared between two tetrahedra, giving an overall formula SiO2. There are many different varieties of quartz,...
. DBD for medical applications such as for treatment of skin diseases and wounds, tumor treatment and disinfection of skin surface are currently under investigation.
The high reactivity of plasma is a result of different plasma components: electromagnetic radiation
Electromagnetic radiation
Electromagnetic radiation is a form of energy that exhibits wave-like behavior as it travels through space...
(UV/VUV
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
, visible light, IR
Infrared
Infrared light is electromagnetic radiation with a wavelength longer than that of visible light, measured from the nominal edge of visible red light at 0.74 micrometres , and extending conventionally to 300 µm...
, high-frequency electromagnetic fields, etc.) on the one hand and ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s, electron
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...
s and reactive chemical species, primarily radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
, on the other. Besides surgical plasma application like argon plasma coagulation
Argon plasma coagulation
Argon plasma coagulation or APC is a medical endoscopic procedure used primarily to control bleeding from certain lesions in the gastrointestinal tract, and also sometimes to debulk tumours in the case of patients for whom surgery is not recommended...
(APC), which is based on high-intensity lethal plasma effects, first and sporadic non-thermal therapeutic plasma applications are documented in literature. However, the basic understanding of mechanisms of plasma effects on different components of living systems is in the early beginning.
Especially for the field of direct therapeutic plasma application, a fundamental knowledge of the mechanisms of plasma interaction with living cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
and tissue is essential as a scientific basis.
First therapeutic approaches of plasma medicine: dermatology and wound healing
Initial experiments confirm the fact that infectious agents can be killed without adverse reactions on surrounding healthy body cells. Furthermore, it is possible to stimulate physiological and biochemical processes in living tissues by plasma treatment under special conditions. This opens the possibility to use plasma to support wound healing as well as to treat several skin diseases. Therefore, application-oriented research is directed to develop an integrated concept of plasma-based wound treatment comprising both superficial wound cleaning and antiseptics and stimulation of tissue regeneration in deeper tissue layers. On a solid scientific basis, further therapeutic plasma applications e.g. in dentistry, or surgery, will be opened during the next yearsPlasma-assisted modification of bio-relevant surfaces
Plasma-assisted modification of bio-relevant materials is an established technique to optimize the biofunctionality of implantsImplant (medicine)
An implant is a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. Medical implants are man-made devices, in contrast to a transplant, which is a transplanted biomedical tissue...
or to qualify polymer surfaces
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
for cell culturing
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
and tissue engineering
Tissue engineering
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions...
. Plasma-based methods and processes for sterilization, decontamination or reprocessing of medical and diagnostic devices, pharmaceutical products or packaging materials are under development worldwide. Both fields are more or less indirect medical plasma applications.
Interdisciplinary basic research on plasma interaction with living matter
Based on knowledge about mechanisms of antimicrobialAntimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
plasma activity, current research in plasma medicine is mainly focussed on the following fields:
- Selective inactivation of infectiousInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
agents in the close presence of living tissue (in vivo antisepsis) - Direct interaction of active plasma components with biochemicalBiochemistryBiochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
and physiologicalPhysiologyPhysiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
processes influencing growth and vitality of cells and tissue - Indirect influencing of cells and tissue via changes of the vital environment (physiological liquids) of cells and tissue through physical plasma.
Combination of plasma technology and plasma diagnostics
Plasma diagnostics
Plasma diagnostics are experimental techniques used to measure properties of a plasma such as temperature and density.-Langmuir probe:Measurements with electric probes, called Langmuir probes, are the oldest and most often used procedures for low-temperature plasmas...
with cell biological
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
, biochemical and chemical analytical techniques
Analytical chemistry
Analytical chemistry is the study of the separation, identification, and quantification of the chemical components of natural and artificial materials. Qualitative analysis gives an indication of the identity of the chemical species in the sample and quantitative analysis determines the amount of...
based on in vitro models using microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
s as well as cell and tissue cultures, will facilitate a sophisticated evaluation of biological plasma effects.
To achieve sustained success of plasma medicine, for any potential therapeutic application optimal plasma composition (radicals, irradiation, temperature, etc.), useful application rate and acceptable relation between desired therapeutic effects and adverse reactions
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
have to be found. This can be realized only in close collaboration between plasma physicists, life scientists and clinical physicians.
Further reading
M. Vandamme, Robert E, Pesnel S, Barbosa E, Dozias S, Sobilo J, Lerondel S, Le Pape A, and Pouvesle JM (2010). Antitumor Effect of Plasma Treatment on U87 Glioma Xenografts: Preliminary Results. Plasma Process. Polym. 7, 264-273.M. Moisan, J. Barbeau, S. Moreau, J. Pelletier, M. Tabrizian, and L’H. Yahia, “ Low Temperature Sterilization Using Gas Plasmas: A Review of the Experiments, and an Analysis of the Inactivation Mechanisms”, Int. J. Pharmaceutics, Vol. 226, pp. 1–21, 2001.
M. Laroussi, A. Fridman, and R. M. Satava, “Plasma Medicine”, Plasma Processes and Polymers, Vol. 5, No. 6, 2008.
M. Laroussi, “ Non-Thermal Decontamination of Biological Media by Atmospheric Pressure Plasmas: Review, Analysis, and Prospects”, IEEE Trans. Plasma Sci., Vol. 30, No. 4, pp. 1409–1415, 2002 .
I.E. Kieft, M. Kurdi, and E. Stoffels, “Reattachment and Apoptosis after Plasma-Needle Treatment of Cultured Cells”, IEEE Trans. Plasma Sci., Vol. 34, No.4, pp. 1331–1336, 2006.
M. Laroussi, D. A. Mendis, and M. Rosenberg, “Plasma Interaction with Microbes”, New Journal of Physics, Vol. 5, pp. 41.1-41.10, 2003.
M. G. Kong, G. Kroesen, G. Morfill, T. Nosenko, T. Shimizu, J. van Dijk and J. L. Zimmermann, “Plasma Medicine: An Introductory Review”, New J. Physics, Vol. 11, 115012, 2009.
M. Laroussi, “Low Temperature Plasmas for Medicine?”, IEEE Trans. Plasma Sci., Vol. 37, No. 6, pp. 714–725, 2009.
Atmospheric-pressure plasma sources: Prospect tools for plasma medicine, K.-D. Weltmann, E. Kindel, T. von Woedtke, M. Hähnel, M. Stieber and R. Brandenburg, Pure Appl. Chem. 82 (2010) 1223–1237
Atmospheric Pressure Plasma Jet for Medical Therapy: Plasma Parameters and Risk Estimation, K.-D. Weltmann, E. Kindel, R. Brandenburg, C. Meyer, R. Bussiahn, C. Wilke and T. von Woedtke, Contrib. Plasma Phys. 49 (2009) 631–640
Antimicrobial treatment of heat sensitive products by miniaturized atmospheric pressure plasma jets (APPJs), K.-D. Weltmann, R. Brandenburg, T. von Woedtke, J. Ehlbeck, R. Foest, M. Stieber and E. Kindel, J. Phys. D: Appl. Phys. 41 (2008) 194008
External links
- plasmatis is the name of a Center of Innovation Competence in Greifswald (Germany) which aims at the basic research of the interactions of physical plasma with cells and tissue
- Plasma research and life sciences work together in the new Campus PlasmaMed located in the farthest north-east of Germany. The main topics of Campus PlasmaMed are: Plasma Medicine, biofunctional surfaces and plasma decontamination
- The Leibniz Institute for Plasma Science and Technology (INP Greifswald e.V.) is the largest non-university institute in the area of low temperature plasmas in Europe
- International Society for Plasma Medicine (ISPM)