Cold Plasmas

Hoffmann et al.
Medical Gas Research 2013, 3:21

http://www.medicalgasresearch.com/content/3/1/21 MEDICAL GAS
RESEARCH
REVIEW Open Access
Cold Atmospheric Plasma: methods of production

and application in dentistry and oncology
Clotilde Hoffmann1, Carlos Berganza1 and John Zhang1,2*
Abstract
Cold Atmospheric Plasma is an ionized gas that has recently been extensively studied by researchers as a possible
therapy in dentistry and oncology. Several different gases can be used to produce Cold Atmospheric Plasma such
as Helium, Argon, Nitrogen, Heliox, and air. There are many methods of production by which cold atmospheric
plasma is created. Each unique method can be used in different biomedical areas. In dentistry, researchers have
mostly investigated the antimicrobial effects produced by plasma as a means to remove dental biofilms and
eradicate oral pathogens. It has been shown that reactive oxidative species, charged particles, and UV photons play
the main role. Cold Atmospheric Plasma has also found a minor, but important role in tooth whitening and
composite restoration. Furthermore, it has been demonstrated that Cold Atmospheric Plasma induces apoptosis,
necrosis, cell detachment, and senescence by disrupting the S phase of cell replication in tumor cells. This unique
finding opens up its potential therapy in oncology.
Keywords: Cold Atmospheric Plasma, Dentistry, Oncology, Reactive Oxidative Species, Apoptosis, Senescence,
Necrosis
Introduction detachment, and cause death in cancer cells, researchers

William Crookes identified plasma in 1879. 99% of the vis- have been interested in finding uses for CAP in dentistry
ible universe is made up of plasma, referred to as the fourth and oncology.
state of matter. The other states of matter are liquid, gas,
and solid (Figure 1). Plasma is a partially ionized gas with Methods of production
ions, electrons, and uncharged particles such as atoms, Several different types of CAP have been developed for bio-
molecules, and radicals. There are two types of plasma: medical uses. Energy is needed to produce and maintain
thermal and non-thermal or cold atmospheric plasma. plasma. Thermal, electric, or light energy can be used. Usu-
Thermal plasma has electrons and heavy particles (neutrals ally, the discharge needed to produce CAP is induced elec-
and ions) at the same temperature. Cold Atmospheric trically. Some methods used to produce CAP include:
Plasma (CAP) is said to be non-thermal because it has elec- Dielectric Barrier Discharge (DBD), Atmospheric Pressure
trons at a hotter temperature than the heavy particles that Plasma Jet (APPJ), Plasma Needle, and Plasma Pencil.
are at room temperature. CAP is a specific type of plasma
that is less than 104°F at the point of application. There are
several methods to produce CAP such as Dielectric Barrier Dielectric barrier discharge
Discharge (DBD), Atmospheric Pressure Plasma Jet (APPJ), In 1857, Siemens was first to conduct experiments on
plasma needle, and plasma pencil. Several different gases Dielectric Barrier Discharge (DBD). DBD has many ap-
can be used to produce CAP such as Helium, Argon, Nitro- plications including: sterilization of living tissue, bacteria
gen, Heliox (a mix of helium and oxygen), and air. Due to inactivation, angiogenesis, surface treatment, and
the ability of CAP to deactivate microorganisms, cause cell excimer formation [1-12]. The dielectric barrier dis-
charge (DBD) consists of two flat metal electrodes that
* Correspondence: [email protected] are covered with dielectric material. A carrier gas moves
1
Department of Physiology, Loma Linda University School of Medicine, Risley between the two electrodes and is ionized to create
Hall, Room 223, Loma Linda, CA 92354, USA
2
Department of Neurosurgery, Loma Linda University School of Medicine, plasma. One electrode is a high voltage electrode and
Loma Linda, CA, USA the other is a grounded electrode. High voltages are
© 2013 Hoffmann et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Hoffmann et al. Medical Gas Research 2013, 3:21 Page 2 of 15
http://www.medicalgasresearch.com/content/3/1/21
Plasma jet
Radio frequency plasma jets
One type of plasma jet, which is employed for bacterial
sterilization, is the Atmospheric Pressure Plasma Jet
(APPJ) [26]. The APPJ consists of two coaxial electrodes
between which a feed gas (mixtures of helium, oxygen,
and other gases) flows at a high rate. The outer electrode
is grounded while Radio Frequency (RF) power (50-
100W) at 13.56 MHz is applied to the central electrode
that creates a discharge. The reactive species produced
exits the nozzle at high velocity and arrives to the area
Figure 1 The four states of matter.
that is to be treated. APPJ has been used for the inacti-
vation of several micro-organisms [27-35].
Koinuma et al. developed the earliest RF cold plasma
jet in 1992 [36]. The cathode is a needle electrode made
required to produce the discharge needed to create the of tungsten or stainless steel with a 1 mm diameter con-
plasma. Alternative Current (AC) high voltages generally nected to a RF source (13.56 MHz). The needle elec-
drive dBD’s with frequencies in the kHz range. The trode lies within a quartz tube whereas the anode
power consumption is between 10 and 100 W [13-16]. electrode is grounded. Depending on the application, he-
There are many variations in the configuration of the lium or argon were mixed with various gases. This group
electrodes, but the concept behind them all remains the published several papers describing its variants and ap-
same. For example, some electrodes are cylindrical in- plications of the plasma jet [37-43]. In 2002, Stoffels
stead of flat and sometimes the dielectric material covers et al. created a miniature atmospheric plasma jet that
only one electrode instead of both. they called plasma needle [44] and created a new version
More recently, Fridman et al. developed the floating- in 2004 [45]. In the former version, the needle was
electrode DBD (FE-DBD) [17]. It is similar to the ori- enclosed in a box and as a result, the samples had to be
ginal DBD and consists of two electrodes: an insulated placed inside of the box to be treated. In the new ver-
high voltage electrode and an active electrode. The dif- sion, the plasma needle consists of a 0.3 mm metal
ference between FE-DBD and DBD is that the second strand diameter with a sharpened tip inside of a Perspex
electrode is not grounded; it is active meaning that the tube. The length of the entire needle is 8 cm and 1.5 cm
second electrode can be human skin, a sample, and remains uncovered by the Perspex tube. The gas used
even an organ. The powered electrode needs to be most frequently is Helium due to its high thermal con-
close to the surface of the second electrode (< 3mm) to ductivity. The gas is then mixed with air at the needle
create the discharge. It has been used on endothelial tip where a micro discharge is created. Gases other than
cells, melanoma skin cancer, and blood coagulation. It Helium are also used [46]. The diameter of the plasma
has also been used in living tissue sterilization and in glow generated is 2 mm. Microplasma is created when
deactivation of Bacillus stratosphericus (Figure 2) RF power at 13.05 MHz ranging between 10 mW and
[18-22]. Plasma jets using a DBD system have also been several watts is applied to the needle. Its small size en-
created [23-25]. ables it to be used to treat small areas where accuracy is
Figure 2 .Diagram of a Dielectric Barrier Discharge and a Floating Electrode Dielectric Barrier Discharge. A presents the formation of
Plasma by the Dielectric Barrier Discharge (DBD) and B presents the Floating Electrode Dielectric Barrier Discharge (FE-DBD).
required like in dentistry [47-52]. It has also been used

to deactivate E. Coli (Figure 3) [53].
Pulsed direct current-driven plasma jets

Laroussi et al. developed a miniature jet that they called
plasma pencil [54]. It consists of a dielectric cylindrical
tube of 2.5 cm in diameter where two disk electrodes of
the same diameter as the tube are inserted. The two
electrodes are separated by a gap (the distance can vary
from 0.3 to 1 cm) and consist of a thin copper ring at-
tached to a dielectric disk. To create the plasma, sub-
microsecond high voltage pulses are applied between the Figure 4 A schematic of the plasma pencil created by
Laroussi et al.
two electrodes while a gas is injected through the holes
of the electrodes. When the discharge is created, a
plasma plume is launched through the hole of the outer
electrode into the air. Because the plasma plume (up to
5cm in length) remains at low temperature (290K), it sterilization purposes. In 1999, Herrmann et al. used
can be touched safely. The electrical power is supplied APPJ with and without oxygen. They observed that the
to the electrodes by a high voltage pulse generator. The D value (the time needed to kill 90% of the microorgan-
high voltage is supplied to the pulse generator by a DC isms) was higher when oxygen was absent [27]. Moreau
voltage supply with variable output. The plasma pencil et al. concluded that oxygen played the main role in the
has been used in the treatment of E. coli, Leukemia cells, sterilization of Bacillus Subtilis [65] whereas Richardson
and P. Gingivalis [55-57]. Forster et al., Zhang et al., and et al. also observed that adding oxygen to the discharge
Wash et al. developed a plasma jet using a DBD config- gas helium made the device more effective at killing bac-
uration (Figure 4) [58-60]. teria [66]. Kuzmichev et al. concluded that the best bac-
tericidal effects were found using moistened oxygen and
Different components of plasma involved in sterilization air.
Laroussi et al. first demonstrated in 1996 that glow dis- Laroussi and Leipold used different gases to deactivate
charge plasma generated at atmospheric pressure is a Bacillus spores: either pure helium, a mix of 97% he-
very effective sterilization agent [61]. The reactive spe- lium/ 3% of oxygen, or air. They observed that the use
cies, charged particles, and UV photons are said to be of pure helium resulted in a D value of over 20 minutes,
the major components involved in sterilization of a wide the use of the mixture of helium and oxygen resulted in
range of gram-positive bacteria, gram-negative bacteria, a D value of 10 minutes, and the use of air resulted in a
spores, biofilms, viruses, and fungi [62-64]. D value of 20 seconds [67]. The oxygen species were
found to play the major role in the sterilization process
Effect of reactive oxidative species due to their strong oxidative effects on the outer struc-
According to several authors, reactive neutral species tures of cells [68].
such as Oxygen, Hydroxyl Radicals, and Nitrogen Diox- Reactive Oxidative Species (ROS) was found to be the
ide play the main role in the use of plasma for major mechanism involved in the deactivation of
Figure 3 .Diagram of a Atmospheric Pressure Plasma Jet and a Plasma Needle. A presents a schematic of the APPJ created by Schütze et al
in 1992 and B presents a schematic of the plasma needle created by Stoffels et al in 2004.
bacteria by the FE-DBD plasma [69]. They observed that wavelengths of UV radiation produced at atmospheric
plasma generates ROS that causes morphological pressure. Choi et al. treated samples with a DBD oper-
changes of E. coli, depolarization of the membrane, lipid ated in air at atmospheric pressure and did not observe
peroxidation, and DNA damage in a dose dependent any UV radiation below 290 nm [76]. Laroussi et al. did
manner. In this study they also used ROS scavengers not observe any UV radiation in the wavelength of 200–
and found no inactivation of E. coli after the plasma 285 nm after using the flowing afterglow of a DBD in air
treatment. This confirms that ROS is the major compo- at atmospheric pressure on spores of B. genus [68].
nent involved in the sterilization process. Kelly-Wintenberg et al. exposed several microorgan-
isms to an atmospheric pressure glow DBD in air. Ac-
Effect of charged particles cording to the authors, the time needed to deactivate the
Kelly-Wintenberg et al. employed an atmospheric pres- microorganism was the same if the samples were in
sure glow discharge for the inactivation of Gram- opaque bags or not, negating that deactivation was due
negative E. coli and used transmission electron micros- to UV radiation [77]. Herrmann et al. treated Bacillus
copy (TEM) to visualize the plasma-induced physical globigii with an atmospheric pressure plasma jet operat-
damage to the microorganism. Plasma exposure rapidly ing in helium/oxygen mixtures and blocked the reactive
disrupts the cell wall and leads to a release of cellular species produced with a quartz window in order to allow
contents in the surrounding medium [70]. only UV radiation to be in contact with the spores. They
Mendis et al. [71] and Laroussi et al. [72] suggested did not observe any significant decrease in the number
that charged particles can play a significant role in the of bacteria after treatment [27]. Birmingham et al. tested
rupture of the outer membrane of bacterial cells. They a plasma blanket and noticed that the plasma blanket
showed that the electrostatic force caused by charge ac- does not generate sufficient photons of the appropriate
cumulation on the outer surface of the cell membrane wavelength and therefore concluded that the deactiva-
could overcome the tensile strength of the membrane tion of the bacterial spore was not the result of the UV
and cause its rupture. Nevertheless, it is more likely to radiation [78]. In the plasma needle created in 2004 by
occur for gram-negative bacteria because of its irregular Stoffels et al., UV emission was quantified between 250
cell surface. Laroussi et al. confirmed this by not observ- and 400 nm with the highest intensities between 305
ing any rupture of the cell of the gram-positive B. Subti- and 390 nm. At these wavelengths, the damage to cells
lis. Furthermore, Fridman et al. showed that charged and tissues is limited [45]. Kostov et al. also concluded
particles play an essential role in sterilization, especially that UV radiation does not play any significant role in
when the plasma is in direct contact with the microor- the sterilization process [79]. The preponderance of the
ganisms. They observed that a direct application of studies suggests that UV radiation does not contribute
plasma resulted in better sterilization efficacy. They con- significantly to the sterilization process.
cluded that it might be possible that charge-induced Nevertheless, some authors do mention the possible
mechanisms contribute to the sterilization process in role of UV radiation in plasma sterilization at atmos-
direct plasma exposure [73]. Stoffels et al. confirmed pheric pressure. Trompeter et al. [80] and Heise et al.
that charged particles play an important role [74]. [81] both used argon plasma and concluded the inactiva-
tion of spores was due to UV radiation. Park et al., Lee
Effect of UV radiation et al., and Boudam et al. also claimed that UV radiation
According to the literature, the role of UV radiation in has a main role [82-84]. Further studies are required to
the sterilization process is still unclear. The presence of investigate and clear up these controversies in the
UV radiation in the plasma strongly depends on the op- literature.
erating pressure. Vacuum plasma at very low pressure
discharges can produce UV radiation in the range of CAP in dentistry
wavelengths known to be involved in sterilization (200– The mouth is a microbial habitat with over 700 species
290 nm) [75]. that live in harmony with the human body [85]. How-
Nevertheless, at atmospheric pressure, plasma does ever, periodontal disease and caries are the two most
not produce UV radiation in adequate wavelengths to common diseases in dentistry. Every year, $60 Billion is
produce sterilization. In 1996, Laroussi et al. compared spent in the United States to treat dental disease. Dental
the efficacy between sterilization with UV radiation pro- caries are defined as the localized destruction of tooth
duced by a low-pressure mercury vapor lamp versus tissue by the acids produced by bacteria. [86]. Caries
glow discharge plasma at atmospheric pressure. They start with small demineralization areas under the en-
concluded that UV radiation was not the first agent in- amel. The demineralization can progress through the
volved in the sterilization process at atmospheric pres- dentine and to the pulp (Figure 5). S. mutans is one of
sure [61]. Choi et al. and Laroussi et al. measured the the major causes of caries [87]. Before filling cavities,
necrotic, infected, and demineralized tissue is removed CAP + saline [110]

by using ozone treatment, mechanical drilling, or laser Carbamide Peroxide + CAP [111]
techniques [88-95]. Unfortunately, these methods can be Plasma plume + 36% H2O2 gel on extracted teeth
destructive as they might remove an excess of healthy [112]
tissue to make sure that the cavity is bacteria free. Peri-
odontal disease is related to dental plaque, which is a Instrument Sterilization-
complex oral biofilm with several microbial species orga-
nized in communities [96]. It leads to the detachment of Removal of biofilms on microstructures titanium
the gum from the tooth as a result of inflammation, [113,114]
which is the body’s natural response to dental plaque. Dental instruments [115]
Several authors have been studying possible use of CAP Ti discs inoculated with biofilms [116]
on dental bleaching, dental disinfection, biofilm removal,
instrument sterilization, and composite restoration (See Composite Restoration-
list of different uses of CAP in dentistry section).
CAP treatment increases dentin/adhesive interfacial
bonding [117]
CAP treatment improves the tensile-shear bond
strength between post and composite [118]
Use of CAP on oral pathogens

A promising application of CAP in dentistry is the disin-
fection of dental cavities due to its high efficiency at de-
activating biofilms. It could offer a less destructive
method to prepare dental caries for filling. Since it
operates at room temperature, it does not cause any pain
or destruction of the tissue. Cold Atmospheric Plasma
could also be used for the treatment of periodontal dis-
ease based on its microorganism deactivation property.
CAP has been shown to be effective at deactivating
biofilms. Goree et al. investigated using a plasma needle
to kill S. mutans, which is the main microorganism
Figure 5 The different components of a tooth [153]. causing dental caries [97]. They observed that the
plasma needle could kill these bacteria after 10 seconds
of treatment. They concluded the plasma needle could
provide an attractive alternative for dental clinical treat-
List of different uses of CAP in dentistry ment. Morris et al. used CAP to deactivate Geobacillus
Deactivation of Biofilms- stearothermophilus and Bacillus cereus microorganisms
[98]. B. cereus, a gram-positive microorganism, has
S. mutans [97] been associated with periodontal disease and food poi-
B. cereus and G. Stearothermophilus [98] soning. G. stearothermophilus is used as a biological in-
L. acidophilus and S. mutans [99] dicator of treatment efficacy in sterilization studies. Both
P. Gingivalis [57] of the microorganisms were in vegetative cells and
S. mutans [100] spores and were treated either with direct or indirect
Root canal disinfection [101] plasma. They concluded that cold plasma is effective in
E. coli, L. casei, S. mutans and C. albicans on agar killing B. cereus vegetative cells and spores at various
and dentine plates [102] time points. G. stearothermophilus vegetative cells were
E. faecalis in the root canal [103] killed with direct and indirect exposure to plasma. In
Ex-vivo biofilms on root canals of extracted teeth [50] 2011, Yang et al. used a cold atmospheric argon plasma
brush to deactivate oral bacteria of Streptococcus mutans
and Lactobacillus acidophilus [99]. They observed that
Tooth Bleaching-
the argon plasma brush was effective at killing bacteria.
Between 11 and 15 seconds (depending on the bacterial
Hydrogen Peroxide + CAP enhanced the tooth supporting media) was needed to deactivate S. mutans. A
bleaching [104-109] little more time was needed to deactivate L. acidophilus:
up to 5 minutes, depending on the bacteria supporting teeth [50]. They divided the teeth into three groups:
media. treatment with the plasma needle, treatment with 6% so-
Mahasneh et al. used Low Temperature Atmospheric dium hypochlorite (an antiseptic), and control. They
plasma to kill Porphyromonas gingivalis, which is a peri- concluded that the plasma needle was effective at killing
odontal pathogen associated with periodontal disease biofilms in extracted teeth. However, using 6% sodium
[57]. The plasma pencil created by Laroussi et al. was hypochlorite is more efficient.
used for the experiment. They observed a significant in-
crease in a dose dependent manner in the inactivation of
P. gingivalis in the treatment group compared with con- Tooth whitening
trol. Kang et al. used RF atmospheric plasma to inacti- Researchers have been interested in the use of CAP in
vate Streptococcus mutans [100]. The gas used was a mix tooth whitening. Hydrogen peroxide is currently used to
of Argon and Hydrogen Peroxide. They observed that whiten teeth [104]. Hydroxyl radicals generated from
the inactivation efficacy was highly dependent on the Hydrogen peroxide play the main role in tooth bleaching
Hydroxyl radical concentration. Moreover, by adding [105]. Some researchers looked for an alternative treat-
hydrogen peroxide to the gas, they decreased the ozone ment and found CAP to be an interesting candidate.
formation that is naturally formed in CAP. Ozone has They either used it in complement with the hydrogen
bactericidal properties, but is toxic which is a disadvan- peroxide treatment or alone. Lee et al. used an atmos-
tage for the use in the clinic. pheric pressure plasma jet for tooth bleaching [106]. The
CAP was also effective at destroying biofilms either on carrier gas used was Helium. 28 extracted teeth were
root canals or on dental slices. Jiang et al. developed a used for the experiment. All of them were cut in half
plasma plume at room temperature [102]. They used it longitudinally and all the pieces were placed in two
to disinfect root canals from extracted human teeth. groups. The dentin and the tooth surface of the treat-
Two teeth were placed at a distance of 5 mm from the ment group received H2O2 + Plasma for 10 minutes
plasma nozzle. One of them was exposed to the helium/ while the dentin and the tooth surface of the control
oxygen plasma for 5 minutes, whereas the other one was only received H2O2 for the same amount of time. The
exposed to the same helium/oxygen flow for five mi- results showed a three fold improvement in tooth
nutes, but without plasma. They observed better results bleaching of the treatment group compared with control.
in the reduction of the biofilms in the tooth treated with The greater efficacy of tooth bleaching in the treated
plasma compared with control. Nevertheless, the plasma group compared with control was reported to be due to
failed to reach the lower zone of the tooth. The authors both the removal of the tooth surface protein and the
explained it by the fact that the plasma plume did not double concentration of Hydroxyl radicals.
have the optimal width and length to effectively treat the Lee et al. also investigated bleaching of teeth stained
lower zone. with coffee or red wine. Using plasma with hydrogen
Rupf et al. used a CAP jet to kill adherent oral mi- peroxide improved the bleaching efficacy by a factor of
crobes, known to cause dental carries [102]. The gas 3.7 for teeth stained with red wine and 3.1 for teeth
mixture used was Helium, Oxygen, and Nitrogen. Four stained with coffee compared with using hydrogen per-
microorganisms were used: E. coli, L. casei, S. mutans, oxide alone [107]. Sun et al. also concluded that using
and C. albicans. These microorganisms were placed on plasma with hydrogen peroxide enhanced tooth whiten-
agar plates and on Dentin slices. The plasma treatment ing compared to hydrogen peroxide alone [108]. Pan
showed antimicrobial efficacy against all of the organ- et al. created a new method of tooth whitening by using
isms. The antimicrobial efficacy was better on agar a Cold Plasma Microjet driven by Direct Current at At-
plates than on dental slices. Moreover, S. mutans, a mospheric Pressure [109]. 60 teeth were chosen and
gram-positive bacteria, showed the strongest resistance were randomly divided into three different groups. In
to plasma-jet treatment. the first one, the teeth were exposed to a saline solution
Lu et al. used a plasma-jet device, which could generate and airflow for twenty minutes. In the second group, the
plasma inside the root canal [103]. They used it on Entero- teeth were exposed to the plasma and saline solution for
coccus faecalis, which is one of the most important bac- twenty minutes. In the last group, the teeth were ex-
teria causing failure of the root-canal treatment. Owing to posed to hydrogen peroxide gel at room temperature for
its low temperature, the plasma could be touched and the same duration of time. They observed that the
placed into the root canal without any pain. A mix of He- whiteness of the teeth of the plasma treated group was
lium & Oxygen was used. They observed that the plasma significantly improved compared to the first and the last
jet was efficient at deactivating Enterococcus faecalis. group. They suggested that the Reactive Species formed
In 2013, Schaudinn et al. used a plasma needle to at the plasma-liquid-tooth interface was the cause for
eliminate ex vivo biofilms on root canals of extracted greater tooth whitening.
Park et al. demonstrated the effect of CAP on an intra- Koban et al. used CAP on biofilms of Streptococcus
coronal tooth stained with blood [110]. They extracted mutans and saliva multispecies grown on titanium discs
single root human teeth and cavities were created artifi- in vitro. They compared the efficacy of sterilizing the
cially. The teeth were then artificially stained by disks with CAP and sterilizing with chlorhexidine diglu-
hemoglobin-rich hemolysed blood. Two groups were used. conate [114]. In contrast to Chlorhexidine digluconate
The control group was treated with 30% hydrogen perox- (CHX), a mouth rinse solution used in dental clinics,
ide in the pulp chamber for 30 min and the experimental treatment with CAP was very effective against S. mutans
group was treated with 30% hydrogen peroxide with CAP. and multispecies saliva biofilms.
The bleaching efficacy of the treated group was approxi- Sung et al. also used CAP to assess the sterilization ef-
mately 2 fold better than that of the control group. fect on dental instruments [115]. They inoculated B.
Tooth bleaching agents are mostly based on hydrogen subtilis and E. coli on diamond burs and polyvinyl silox-
peroxide and carbamide peroxide where light sources ane materials. Then they exposed them to the plasma
can be used in combination. Light sources can increase for a different length of time (from 30 to 240 seconds).
the effectiveness of the tooth whitening. Nam et al. used They compared the plasma device efficacy with the UV
a Plasma jet on forty extracted human molar teeth with sterilizer. The plasma device decreased the colony-
intact crowns [111]. The forty teeth were randomly di- forming unit (CFU) for both E. coli and B. subtilis sig-
vided into four groups (n=10) and were treated with nificantly on both diamond burs and polyvinyl siloxane
Carbamide peroxide + CAP, Carbamide peroxide + materials. The atmospheric pressure of non-thermal air
Plasma Arc Lamp (PAC), Carbamide peroxide + diode plasma showed better sterilization rates than the UV
laser, or Carbamide Peroxide alone (control). They ob- sterilizer.
served CAP was the most effective at bleaching teeth. Idlibi et al. treated Ti discs inoculated with biofilms
Moreover, they observed that CAP does not damage the with CAP [116]. The biofilms were divided randomly
tooth due to its low temperature. among the following treatments: CAP, diode laser, air-
Laroussi et al. used a plasma plume on thirty extracted abrasion, and chlorhexidine. They observed CAP treat-
human teeth randomized into two groups: Group I re- ment decreased the quantity of the biofilms the most
ceived plasma plume + 36% H2O2 gel for 10, 15 and among all the treatments. Nevertheless, CAP did not
20 min and Group II received 36% H2O2 gel only for the succeed in completely removing the biofilms.
same time duration [112]. They observed a statistically
significant increase in the whitening of the teeth after Dental composites
exposure to CAP + 36% H2O2 gel, compared with 36% Dental composites are currently used to fill cavities.
H2O2 only, in the 10 and 20 min groups. The Some researchers investigated CAP in composite resto-
temperature in both treatment groups remained under rations. The plasma generates reactive species that arrive
80°F throughout the study, which is below the thermal on the surface of the composite resulting in both micro-
threat for vital tooth bleaching. structural and surface chemistry modifications that im-
prove adhesive bonding. They observed plasma
Sterilization of dental instruments treatment increases bonding strength at the dentin/com-
Autoclaves and UV sterilizers are currently used to posite interface that enables it to last longer on teeth.
sterilize dental instruments. To develop a dental steril- Ritts et al. investigated a non-thermal atmospheric
izer that can sterilize most materials including metals, plasma brush on dental composite restoration [117].
rubber, and plastics, researchers have investigated CAP They observed that atmospheric cold plasma brush
as a universal sterilizer. Rupf et al. employed a CAP jet (ACPB) treatment could modify the dentin surface and
to remove biofilms on micro-structured titanium [113]. increase dentin/adhesive interfacial bonding. Yavrich
They created biofilms by intraoral exposure on micro- et al. studied the effects of plasma treatment on the
structured titanium discs. A mini plasma device 1.5 cm shear bond strength between fiber reinforced composite
wide and 2.5 cm tall was used with helium as the carried posts and resin composite for core buildup and con-
gas. By using fluorescence microscopy and Scanning cluded that plasma treatment appeared to increase the
Electron Microscopy (SEM) they observed a complete tensile-shear bond strength between post and compos-
disinfection of the biofilms with a single plasma treat- ites [118].
ment. Nevertheless, a combination of plasma with air/
surface spray resulted in a complete biofilm removal. Effects of CAP on malignant cells
Using an extra plasma treatment at the end even in- CAP and mammalian cells
creased the probability of the complete removal of the Few studies have been performed on the effect of CAP
biofilm. They also showed that plasma was superior to on eukaryotic cells thus far. Eukaryotic cells are defined
chlorhexidine in biofilm removal. as cells where the genetic material is inside the nucleus.
Some researchers observed either cell detachment, de- Effect of CAP on various cancers
crease of cell migration, apoptosis, or necrosis on several A few in vitro and in-vivo studies have been published
types of cells depending on the power and the time of by researchers regarding CAP use in cancer. In an
exposure to plasma. Necrosis is defined as an unpro- in vitro study, Fridman et al. used a FE-DBD plasma
grammed death of cells in living tissue. This leads to in- treatment to treat Melanoma cancer cells [20]. They ob-
flammation by releasing intracellular content. In served either apoptosis or necrosis depending on the
contrast with necrosis, apoptosis is a programmed cell dose of the treatment. Melanoma cells, treated by
death process resulting in no inflammation. Different plasma at low dose, developed apoptosis several hours
groups have conducted in vitro experiments with fibro- post treatment. At higher dosage, melanoma cells devel-
blasts, endothelial cells, ovarian cells, human hepato- oped necrosis. Apoptosis was also observed on cultured
cytes, and smooth muscle cells. Stoffels et al. used a human breast cancer cells treated with a pulsed atmos-
plasma needle on Chinese Hamster ovarian cells and ob- pheric pressure plasma jet used with Heliox [127]. At
served different results depending on the power and the low plasma dosage apoptosis was observed while at a
time of exposure. For exposure times longer than 10s higher dose, necrosis was observed. Thiyagarajan et al.
and powers higher than 0.2W, necrosis was observed. observed that CAP can cause cell death in leukemia can-
With lower doses of exposure to the plasma, apoptosis cer cells (THP-1 cells), and there is a dose dependent re-
was observed. With power level at about 50 mW and an sponse in the induction of cell death. They also observed
exposure time of 1s, the cells detached from the sample that higher treatment doses cause necrosis, while lower
without undergoing apoptosis [119]. Yonson et al. [120] treatment doses induce apoptosis [128]. In 2012, Par-
also showed detachment of human hepatocytes (HepG2) tecke et al. observed Tissue Tolerable Plasma (TTP)
after CAP treatment. Shashurin et al. used a plasma jet treatment significantly induces apoptosis in pancreatic
on fibroblast cells and observed cell detachment at cancer cells in vitro, with treatment duration of 10 sec-
medium plasma treatment levels [121]. Kieft et al. [122] onds showing the strongest effect [129].
induced apoptosis in 3T3 mouse fibroblast cells and in Walk et al. used a CAP on neuroblastoma cells
another study they used a plasma needle for treatment in vitro [130] and concluded that CAP decreases meta-
of mammalian endothelial and smooth muscle cells. At bolic activity, induces apoptosis, and reduces numbers of
lower doses cell detachment was observed while at viable cancer cells in direct proportion to the duration
higher doses necrosis was observed [123]. Some re- of treatment. Kaushik et al. used an Atmospheric Pres-
searchers observed that CAP decreases cells migration sure non-thermal plasma jet on T98G brain cancer cells
of both fibroblasts and epithelial cells by increasing in- [131]. They observed the mortality percent of T98G cells
tegrin activation [124]. directly depends on exposure time. As plasma exposure
increases, the plasma treatment increases cell death and
inhibits the colony formation capability of the T98G cell
CAP and malignant cells population. They observed that plasma treatment in-
Because of the effect of CAP on mammalian cells, re- hibits the colony formation capabilities of T98G cells at
searchers have been interested in using it on malig- all doses.
nant cells also. The conventional therapies for Glioblastoma is the most aggressive brain tumor in
cancerous diseases are based on removal of the adults. Therapy with Temozolomide (TMZ) is efficient
tumor, chemotherapy, or radiation. Nevertheless some only when patients have methylation of the MGMT gene
cancers remain hard to eradicate. In-vitro and in-vivo in the tumor. Köritzer et al. used plasma produced on a
studies have been performed on the efficacy of CAP Surface Micro-Discharge (SMD) electrode on the human
at killing cancer cells. The results of the pilot studies glioblastoma cell lines LN18, LN229 and U87MG [132].
performed by several research groups confirmed that The cell lines U87MG and LN229 do not express the
treatment with low-temperature plasma is able to in- MGMT protein, while the cell line LN18 expresses the
duce several modes of cell death including apoptosis MGMT protein. TMZ was also used as a treatment on
and necrosis. They also noticed decreased cell migra- the human glioblastoma cell lines either alone or in
tion and induction of senescence in cancer cells. Re- combination with CAP. They observed TMZ was only
garding the mechanism of the Atmospheric Pressure efficient on the cell lines with MGMT when used alone.
Plasma therapy on cancer cells, the hypothesis is that They observed that previous CAP treatment restores the
the ROS plays the main role. ROS are well known to sensitivity of TMZ resistant glioma cells. 60 seconds of
be harmful to cells inducing apoptosis, senescence, or CAP treatment combined with 100 mM or 200 mM
cell cycle arrest [125]. Sensenig et al. proposed that TMZ showed a statistically significance increase in indu-
ROS is the mechanism through which CAP induces cing a cell cycle arrest in G2/M phase compared with
apoptosis [126]. TMZ treatment alone.
Laroussi et al. used a plasma pencil on non-adherent growth rate was decreased and median survival of the
leukemia cancer cells and Helium was the carrier gas mice in the treatment group was almost two fold from
used [133]. CCRF-CEM cells, which are non-adherent 15 to 28 days. CAP treatment resulted in a dramatically
leukemia cancer cells, were suspended in media solution improved survival compared to the control group.
and treated with CAP for 0–10 minutes. They observed In another in-vivo study, Kim et al. demonstrated no
a dose dependent response in the induction of cell death. initial reduction in melanoma size, but did show CAP's
They suppose that a longer exposure to plasma results ability to inhibit tumor growth in mice [137]. Female
in an increase in the reactive species formation. The de- mice between 6 and 8 weeks old were subcutaneously
layed effect of plasma exposure on leukemia cells might injected with B16F0 cells. After tumors reached a size of
be attributed to the initiation of an intracellular signaling about 40 mm3, the mice were treated with a micro-
cascade that leads to programmed cell death. plasma for 5 seconds each either one time or four times
Some researchers have studied the effect of CAP on for four consecutive days. They then measured the
the invasion activity in colorectal cancer [134]. They length and width of the tumors every 2 to 3 days and
concluded that CAP significantly inhibited cell migration they calculated the tumor volume. They observed no an-
and invasion in SW480 colorectal cancer cells. However, titumor effect for the one-time treatment. However, the
the best results were when they were treated with a mix four-time treatment was effective at inhibiting tumor
of Helium plus Oxygen compared to control or Helium growth (Table 1).
only. They also observed that increasing plasma voltage Vandamme et al. used FE-DBD plasma on U87-
improves the results. bearing mice [138]. They started the treatment when the
Cold atmospheric plasma can be used as a new strat- tumor reached 150 ± 50 mm3 corresponding to Day 0.
egy to induce senescence in melanoma cells [135]. Some Mice received a daily plasma treatment for 6 minutes for
researchers used a ‘miniFlat-Plaster’ that uses the flexible five consecutive days. At day 6 they measured the tumor
and scalable Surface Micro Discharge (SMD) technology volume and observed a significant reduction of 56% for
for plasma production in air. Melanoma cells were the treatment group compared with the control. They
treated for either one or two minutes. Two minutes of also performed a bioluminescence imaging (BLI) of the
CAP treatment resulted in about 50% apoptosis in mel- tumor on Day 0 (D0) and Day 6 (D6). They calculated
anoma cancer cell lines. On the contrary, 1 min of CAP the ratio D6/D0 of BLI intensity, corresponding to the
treatment was not enough to induce apoptosis, but it tumor activity between the beginning and the end of the
created senescence (a permanent cell cycle arrest, con- treatment. They observed in the control group a 24-fold
sidered as a good mechanism which prevents aged or BLI intensity increase, whereas in the treatment group,
abnormal cells from expansion) and as a result stopped BLI intensity only increased sevenfold. They also evalu-
proliferation. Kim et al. used Atmospheric non-thermal ated the long-term effect of the plasma treatment. After
plasma to treat HCT-116 colorectal cancer cells and also plasma completion, tumors started to grow again, but
observed CAP induced cell growth arrest and apoptosis. slowly compared with the control group. They also ob-
Moreover, plasma reduced cell migration and invasion served a decrease in mortality for the treatment group of
activities [136]. 58%. These results showed significant anti-tumor prop-
erty of the CAP treatment.
In-vivo studies on the use of CAP in cancer Keidar et al. applied a plasma jet to 10 nude mice
Walk et al. performed an in vivo study of neuroblastoma bearing subcutaneous bladder cancer (SCaBER) and to 8
cells injected in mice [130]. Mice were injected with mice with B16 melanoma cells. In the bladder cancer
Neuro2a cells and treated with CAP. 7 treated mice re- group, they observed that a single treatment with CAP
ceived 5 min of CAP while 7 control mice received no of 5 minutes led to tumor ablation. They also observed
therapy after inoculation. CAP initially ablated the tu- that tumors of about 5mm in diameter are ablated after
mors. Although tumors recurred in some mice, their 2 min of single time plasma treatment, whereas larger
Table 1 In vitro and in vivo studies performed in Oncology with CAP

Studies performed Types of cancer
in Oncology
In vitro studies Melanoma cells [20], Human Breast cancer cells [127], Leukemia cells (THP-1 cells) [128], Pancreatic cancer cells [129],
Neuroblastoma cells [130], T98G brain cancer cells [131], human glioblastoma cell lines LN18, LN229 and U87MG [132],
CCRF-CEM cells (non-adherent leukemia cells) [133], Colorectal cancer cells (SW480 cells) [134], Melanoma cells [135],
Colorectal cancer cells (HCT-116 cells) [135], lung cancer (SW900) cell lines and murine melanoma cells [143], TC-1
lung carcinoma cells [145], Murine melanoma B16F0 tumor cells [144], B16 cancer cells and COLO320 cancer cells [144],
Lung cancer cell lines (H460 and HCC1588) [145]
In vivo studies Pancreatic tumor [129], Neuroblastoma [130], Melanoma [137], Glioma [138], Bladder cancer tumor and melanoma [139]
tumors decreased in size. Moreover, the ablated tumors Between S and G2 phases and between G2 and M
did not grow back, while partially removed tumors phases we can find checkpoints that check if the pro-
started growing back a week after treatment without cesses at each phase of the cell cycle have been accur-
reaching the original size even after 3 weeks post- ately completed before progressing into the next phase.
treatment. They also observed good outcomes for the Volotskova et al. found that CAP delayed progression of
mice inoculated with melanoma. After the treatment skin cancer cells by hindering them at the checkpoint
with CAP for five minutes, they observed the tumor between G2 and M phases. It correlated with the in-
growth rates were markedly decreased and the median crease of cH2A.X that is a marker showing damage in
survival was 33.5 days while it was of 24.5 days for the the S phase of the cycle.
control group [139]. Keidar et al. used CAP in vitro on normal human
Partecke’s in-vivo experiment using TTP induced Bronchial epithelial cells (NHBE), lung cancer (SW900)
apoptosis only in the top cell layers of pancreatic tumor cell lines, murine melanoma cells, and primary macro-
showing a depth of effective tissue penetration of up to phages. They observed cell detachment of 60–70% of
60μm [129]. Some improvement needs to be done to SW900 cancer cells treated with plasma, while no de-
enable plasma to reach deeper in the tumor. tachment was observed in the treated zone for the nor-
mal human Bronchial epithelial cells (NHBE). Plasma
CAP in cancer therapy conjugated to gold nanoparticles treatment leads to a significant reduction in SW900 cell
Kim et al. created a novel approach to treat cancerous number, whereas NHBE cell count remains almost the
cells by incubating cancer cells with gold nanoparticles same. Concerning the murine macrophages and B16
making them more vulnerable to CAP treatment. They melanoma cells, they observed plasma selectivity for
bound Gold nanoparticles (GNP) to G361 melanoma murine melanoma cancer cells while murine macro-
skin cancer cells with an anti-FAK antibody. FAK anti- phages were not affected [139].
body is a protein overexpressed in G361 melanoma cells Kim et al. used a microplasma jet device on mouse
compared to normal tissues. They observed a five-fold TC-1 lung carcinoma and CL.7 fibroblast cells. They ob-
improvement of melanoma cell death over using plasma served more apoptotic activity in TC-1 lung carcinoma
alone by using air plasma with gold nanoparticles bound cells compared with the CL.7 fibroblast cells treated with
to anti-FAK antibodies [140]. Later, they investigated the the same dosage and same duration. They concluded
effect of GNP conjugates with anti-EGFR antibody and that the TC-1 tumor cells are more sensitive to plasma
anti-TFR antibody treated with CAP for the selective treatment than CL.7 fibroblast cells under these experi-
treatment of cancerous cells [141]. Epidermal growth re- mental conditions. They even noticed for certain plasma
ceptor (EGFR) and transferring receptor (TFR) are over- dose conditions, the microplasma jet induced only apop-
expressed in several oral cancer cells. Therefore, anti- tosis of the TC-1 lung carcinoma cells. This micro-
EGFR antibody and anti-TFR antibody were conjugated plasma could be used to selectively kill TC-1 lung
to GNPs for targeting oral cancers. They observed a sig- carcinoma cells [143]. In another study, they also used a
nificant improvement of oral carcinoma cell death over micro-plasma to treat both Murine melanoma B16F0
using plasma alone by using CAP with bound nanoparti- tumor cells and murine fibroblast CL.7 cells for 0–20
cles to anti-EGFR antibody or anti-TFR antibody. seconds respectively [144]. They observed the murine
melanoma tumor cells were more sensitive to plasma
CAP selectivity of cancer cells treatment than murine fibroblast cells under specific
Despite the good results observed on in vitro and a few plasma dose conditions. The plasma treatment induced
in vivo studies, more work is required to make CAP use- more apoptosis in B16F0 tumor cells than in CL.7 cells
ful in the clinic. Finding a therapy for cancer remains when the treatment was lower than 20 seconds.
challenging because it has to selectively attack only the Gweon et al. used a microplasma jet on both meta-
cancer cells and let the normal cells live. Some re- static cancerous SK-HEP-1 and normal THLE-2 cells for
searchers found that the cancer cells are more sensitive a duration of two minutes with Helium as a carrier gas
to CAP treatment than normal cells, which could make [145]. They observed that the cancer cells had a better
CAP an ideal cancer therapy. ability to detach compared to normal cells after treat-
Volotskova et al. showed that the cancer cells are more ment. According to the biochemical and biophysical as-
susceptible to the effects of CAP because a higher per- says, cancer cells seemed to have weaker adhesion and
centage of cells are in the S phase of the cell cycle [142]. different responses against plasma treatment compared
The cell cycle is defined as a series of events that takes to the normal cells.
place in a cell leading to its division and replication. The Georgescu et al. observed no apoptosis in macrophage
cell cycle consists of four different phases: G1, S (Syn- cells treated with CAP while apoptosis was observed on
thesis of DNA), G2 (Interphase) and M phase (Mitosis). B16 cancer cells and COLO320 cancer cells [146]. Amdt
et al. also observed that normal melanocytes are less by approximately 2-fold and 2.6-fold in HeLa cells
sensitive to CAP therapy in comparison with tumor cells treated with N2 and air plasma jets, respectively, com-
derived from primary or metastatic melanomas [135]. pared with untreated cells. Interestingly, they observed
Panngom et al. treated Lung cancer cell lines (H460 and depolarization of the mitochondrial membrane potential
HCC1588) and lung normal cell lines (MRC5 and L132) which is an early event of apoptosis. The depolarization
with non-thermal DBD plasma [147]. They observed results in mitochondrial membrane permeability, and as
higher apoptotic cell death in lung cancer cell lines than a result releases proapoptotic factors. They noticed a de-
that in lung normal cell lines treated with plasma. crease of the apoptotic effect of the CAP by using scav-
engers of ROS. It suggests that the apoptotic effects of
Molecular mechanism of the action of CAP on cancer cells the plasma jet may be mediated by ROS. By using
Tuhvatulin et al. have been interested in the mechanism caspase-3 and caspase-9 inhibitors, they also noticed a
involved in the cell death after plasma exposition. They diminution of cell death showing the potential involve-
observed that CAP treatment of human colon carcinoma ment of mitochondria in apoptosis.
cells (HCT116) induces activation of protein p53, known Panngom et al. also concluded that mitochondria may
to initiate cell death via the p53-dependant pathway. be involved in the apoptosis process following lung can-
They found that the activation of caspase 3 depends on cer cells exposure with non-thermal DBD plasma [147].
the presence of p53. They concluded that treatment of They observed that Mitochondrial Membrane Potential,
human colon carcinoma cells by CAP results in apop- mitochondrial enzyme activity and respiration rate were
tosis dependent of p53 [148]. Nevertheless, more studies significantly decreased in cancer cells with CAP treat-
need to be performed regarding the type of damage in ment compared with the normal lung cells treated with
cells resulting in p53 activation. plasma. They also observed an alternation of the morph-
Yan et al. observed plasma treatment increases the ology of mitochondria.
percentage of apoptotic cells being associated with cell Yan et al. proposed a mechanism of action of CAP on
cycle arrest at the G2/M phase. They found the expres- cancer cells in 2012 [152]. They observed CAP can con-
sion of the p21 CDK inhibitor (cell cycle inhibitor) and trol the intracellular concentrations of ROS, NO, and
the protein p53 are increased [149]. lipid peroxide. They showed that the concentrations of
Vandamme et al. treated human glioblastoma ROS, NO, and lipid peroxide are directly related to the
(U87MG) and human colon carcinoma (HCT-116) cells mechanism of liver hepatocellular carcinoma (HepG2)
with CAP. They observed that CAP generated a large cell death, which involves several steps. First, the plasma
amount of reactive oxidative species (ROS) that is the generates NO species, which increases the NO concen-
main cause of cell death. After CAP treatment a cell tration in the extracellular medium. Then, due to a dif-
cycle arrest in S and G2/M phase was observed. DNA fusion process, the intracellular NO concentration
damage is observed 1 hour after treatment, suggesting increases which leads to the increase of the intracellular
this is a consequence of the treatment. They concluded ROS concentration. Finally the oxidative stress creates
that formation of DNA damages in treated cells leads to lipid peroxidation that injures the cell. The combined
cell cycle arrest and finally to apoptosis [150]. They also action of NO, ROS, and lipid peroxide species results in
conducted an in vivo experiments on U87MG (human HepG2 cell death. The increased concentrations of NO,
glioblastoma cells) bearing mice and observed a signifi- ROS, and lipid peroxide during the plasma exposure
cant inhibition of tumor growth (40%) at the end of the correlated with the decreasing numbers of viable cells.
treatment compared with control group [138]. They hy- (See list of mechanisms of CAP on cancer cells).
pothesized that DNA strand break formation mediates
accumulation of tumor cells in S phase causing apop- List of mechanisms of CAP on cancer cells
tosis in the whole tumor. It suggests that plasma compo-
nents either penetrate in the tissue or induce ROS Activation of p53 protein [148]
release inside of the tissue. It is encouraging, but the Activation of p21 CDK inhibitor [149]
exact mechanism remains unclear. Cell cycle arrest at the G2/M and S phase
Ahn et al. observed that treatment with nitrogen gas [142,149,150]
(N2) and air plasma jet induced apoptosis via ROS gen- ROS leads to DNA damages leading to cell cycle
eration and dysfunction of mitochondria in human cer- arrest [150]
vical carcinoma (HeLa) cells [151]. They used a plasma Apoptosis induced via ROS generation and
jet with either air or N2 on human cervical carcinoma dysfunction of mitochondria [151]
HeLa cells. The cells were treated for 2 to 8 minutes. Mitochondrial Membrane Potential, mitochondrial
They observed N2 and air plasma jets induce apoptosis enzyme activity and respiration rate are significantly
in a dose-dependent manner. The level of ROS increased decreased in cancer cells after CAP treatment [147]
CAP can control the intracellular concentrations of 4. Chiper AS, Chen W, Mejlholm O, Dalgaard P, Stamate E: Atmospheric
ROS, NO, and lipid peroxide [152] pressure plasma produced inside a closed package by dielectric barrier
discharge in Ar/CO2 for bacterial inactivation of biological samples.
Plasma Sources Sci Technol 2011, 20:10.
The exact mechanism of action of CAP on cells still 5. Chiang MH, Wu JY, Li YH, Wu S, Chen SH, Chang CL: Inactivation of E. coli
remains unclear. What cell signals CAP induces has not and B. subtilis by a parallel-plate dielectric barrier discharge jet. Surf Coat
Technol 2010, 204:3729–3737.
been clarified so far. A better understanding regarding 6. Kogelschatz U, Eliasson B, Walter E: From ozone generator to flat
the signaling events induced by CAP treatment on cells television screens: history and future potential of dielectric barrier
is required to find the optimal dose and type of plasma discharges. Pure Appl Chem 1999, 71:1819–1828.
7. Kogelschatz U, Hirth M, Eliasson B: Ozone synthesis from oxygen in
to be used successfully in the clinic. dielectric barrier discharges. J Phys D: Appl Phy 1987, 20:1421–1437.
8. Wagner HE, Brandenburg R, Kozlov KV, Sonnenfeld A, Michel P, Behnke JF:
Conclusion The barrier discharge: basic properties and application to surface
treatment. Vacuum 2003, 71:417–436.
CAP has a bright future in dentistry and oncology due 9. Boyd IW, Zhang ZY, Kogelschatz U: In Development and applications of UV
to its anti-microbial properties and its cell death proper- excimer lamps, Photo-Excited Processes, Diagnostics and Applications. Edited
ties on cells. Concerning dentistry, studies of CAP by Peled A. The Netherlands: Kluwer Academic; 2003:161–199.
10. Lomaev MI, Sosnin EA, Tarasenko VF, Shitts DV, Skakun VS, Erofeev MV:
showed promising results in tooth bleaching, deactiva- Capacitive and barrier discharge excilamps and their applications.
tion of biofilms in teeth, instrument sterilization, and in Instrum Exp Tech 2006, 49:595–746.
composite restoration. Nevertheless, progress needs to 11. Tarasenko VF: Excilamps as efficient UV-VUV light sources. Pure Appl Chem
2002, 74:465–469.
be made concerning the ideal width and depth of the 12. Morimoto Y, Sumitomo T, Yoshioka M, Takemura T: Recent progress on UV
plume of plasma to enable the treatment to reach lower lamps for industries. Ind Appl Confer, IAS, IEEE 2004, 2:1008–1015.
in teeth. Promising findings obtained from in vivo and 13. Oppenlander T, Sosnin E: Mercury free (VUV) and UV excil lamps: lamps
of the future. IUVA news 2005, 7:16–20.
in vitro studies of CAP in oncology show that CAP will 14. Eliasson B, Kogelschatz U: Non-equilibrium volume plasma chemical
find its niche in the treatment of cancer patients in the processing. IEEE Trans Plasma Sci 1991, 19:1063–1077.
future. However, more studies need to be performed re- 15. Pietsch GJ: Peculiarities of dielectric barrier discharges. Contrib Plasma
Phys 2001, 41:620–628.
garding the mechanism of action. 16. Kogelschatz U: Dielectric-barrier discharges: Their history, discharge
physics, and industrial applications. Plasma Chem Plasma Proc 2003,
Abbreviations 23:1–46.
AC: Alternative Current; APPJ: Atmospheric Pressure Plasma Jet; 17. Chirokov A, Gutsol A, Fridman A: Atmospheric pressure plasma of
BLI: Bioluminescence Imaging; CAP: Cold Atmospheric Plasma; CFU: Colony dielectric barrier discharges. Pure Appl Chem 2005, 77:487–495.
Forming Unit; DC: Direct Current; DBD: Dielectric Barrier Discharge; FE- 18. Fridman G, Peddinghaus M, Ayan H, Fridman A, Balasubramanian M, Gutsol
DBD: Floating Electrode Dielectric Barrier Discharge; GNP: Gold Nanoparticles; A, Brooks A, Friedman G: Blood coagulation and living tissue sterilization
NO: Nitrogen Oxide; RF: Radio Frequency; ROS: Reactive Oxidative Species; by floating-electrode dielectric barrier discharge in air. Plasma Chem
SEM: Scanning Electron Microscopy; SMD: Surface Micro Discharge; Plasma 2006, 26:425–442.
TEM: Transmission Electron Microscopy; TMZ: Temozolomide; TTP: Tissue 19. Kalghatgi SU, Fridman G, Fridman A, Friedman G, Clyne AM: 2008 Non-
Tolerable Plasma. thermal dielectric barrier discharge plasma treatment of endothelial
cells. Conf Proc IEEE Eng Med Biol Soc 2008, 2008:3578–3581.
Competing interests 20. Fridman G, Shereshevsky A, Jost MM, Brooks AD, Fridman A, Gutsol A,
The authors declare that they have no competing interests. Vasilets V, Friedman G: Floating electrode dielectric barrier discharge
plasma in air promoting apoptotic behavior in melanoma skin cancer
Authors’ contributions cell lines. Plasma Chem Plasma Process 2007, 27:163–176.
CH identified the subject, did literature search, and wrote the initial draft. CB 21. Cooper M, Fridman G, Fridman A, Joshi SG: Biological responses of Bacillus
helped with organization and revised the manuscript. JZ-Role included re- stratosphericus to floating electrode-dielectric barrier discharge plasma
view design and manuscript proof reading. All authors read and approved treatment. J Appl Microbiol 2010, 109:2039–2048.
the final manuscript. 22. Joshi SG, et al: Control of methicillin-resistant Staphylococcus aureus in
planktonic form and biofilms: a biocidal efficacy study of nonthermal
Acknowledgments dielectric-barrier discharge plasma. Am J Infect Control 2010, 38:293–301.
We thank Damien Bachelet for his work on the figures. 23. Teschke M, Kedzierski J, Finantu-Dinu EG, Korzec D, Engemann J: High-
speed photographs of a dielectric barrier atmospheric pressure plasma
Received: 3 July 2013 Accepted: 5 September 2013 jet. IEEE Trans Plasma Sci 2005, 33:310.
Published: 1 October 2013 24. Chen G, Chen S, Zhou M, Feng W, Gu W, Yang S: The preliminary
discharging characterization of a novel APGD plume and its application
References in organic contaminant degradation. Plasma Sources Sci Technol 2006,
1. García-Alcantara E, López-Callejas R, Morales-Ramírez PR, Peña-Eguiluz R, 15:603.
Fajardo-Muñoz R, Mercado-Cabrera A, Barocio SR, Valencia-Alvarado R, 25. Kim DB, Rhee JK, Moon SY, Choe W: Study of geometrical and operational
Rodríguez-Méndez BG, Muñoz-Castro AE, de la Piedad-Beneitez A, parameters controlling the low frequency microjet atmospheric pressure
Rojas-Olmedo IA: Accelerated mice skin acute wound healing in vivo by plasma characteristics. Appl Phys Lett 2006, 89:061502.
combined treatment of argon and helium plasma needle. Arch Med Res 26. Schütze A, Jeong JY, Babayan SE, Park J, Selwyn GS, Hicks RF: The
2013, 44(3):169–177. atmospheric-pressure plasma jet: a review and comparison to other
2. Ziuzina D, Patil S, Cullen PJ, Keener KM, Bourke P: Atmospheric cold plasma plasma sources. IEEE Trans Plasma Sci 1998, 26:1685.
inactivation of Escherichia coli in liquid media inside a sealed package. 27. Herrmann HW, Henins I, Park J, Selwyn GS: Decontamination of chemical
J Appl Microbiol 2012, 114(3):778–787. and biological warfare (CBW) agents using an atmospheric pressure
3. Arjunan KP, Clyne AM: Hydroxyl radical and hydrogen peroxide are plasma jet (APPJ). Phys Plasmas 1999, 6:2284.
primarily responsible for dielectric barrier discharge plasma induced 28. Abramzon N, Joaquin JC, Bray J, Brelles-Marino G: Biofilm destruction by RF
angiogenesis. Plasma Process Polym 2011, 8:1154–1164. high-pressure cold plasma jet. IEEE Trans Plasma Sci 2006, 34(4):1304–1309.
29. Fricke K, Koban I, Tresp H, Jablonowski L, Schröder K, Kramer A, Weltmann 52. Sladek REJ, Baede TA, Stoffels E: Plasma-needle treatment of substrates
K-D, von Woedtke T, Kocher T: Atmospheric pressure plasma: a high- with respect to wettability and growth of Escherichia coli and
performance tool for the efficient removal of biofilms. PLOS ONE 2012, Streptococcus mutans. IEEE T Plasma Sci 2006, 34:1325–1330.
7(8):e42539. doi:10.1371/journal.pone.0042539. 53. Sladek REJ, Stoffels E: Deactivation of Escherichia coli by the plasma
30. Niemira BA: Cold plasma reduction of salmonella and escherichia coli needle. J Phys D-Appl Phys 2005, 38:1716–1721.
O157:H7 on almonds using ambient pressure gases. J Food Sci 2012, 54. Laroussi M, Lu X: Room temperature atmospheric pressure plasma plume
77(3):M171–M175. for biomedical applications. Appl Phys Lett 2005, 87:113902.
31. Tseng S, Abramzon N, Jackson JO, Lin W-J: Gas discharge plasmas are ef- 55. Laroussi M, Tendero C, Lu X, Alla S, Hynes WL: Inactivation of bacteria by
fective in inactivating Bacillus and Clostridium spores. Appl Microbiol Bio- the plasma pencil. Plasma Processes Polym 2006, 3:470–473.
technol 2012, 93:2563–2570. 56. Barekzi N, Laroussi M: Dose-dependent killing of leukemia cells by low-
32. Alkawareek MY, Algwari QT, Gorman SP, Graham WG, O'Connell D, et al: temperature plasma. J Phys D Appl Phys, 45:422002. doi:10.1088/0022-3727/
Application of atmospheric pressure nonthermal plasma for the in vitro 45/42/422002.
eradication of bacterial biofilms. FEMS Immunol Med Microbiol 2012, 57. Mahasneh A, Darby M, Tolle SL, Hynes W, Laroussi M, Karakas E: Inactivation
65:381–384. of Porphyromonas gingivalis by low-temperature atmospheric pressure
33. Jiang C, Schaudinn C, Jaramillo DE, Webster P, Costerton JW: In vitro plasma. Plasma Med 2011, 1(3–4):191–204.
antimicrobial effect of a cold plasma jet against Enterococcus faecalis 58. Foster JE, Weatherford B, Gillman E, Yee B: Underwater operation of a DBD
biofilms. ISRN Dentistry 2012, 2012:295736. plasma jet. Plasma Sources Sci T 2010, 19(2):025001.
34. Matthes R, Bekeschus S, Bender C, Hübner N-O, Kramer A: Pilot-study on 59. Zhang J, Sun J, Wang D, Wang X: A novel cold plasma jet generated by
the influence of carrier gas and plasma application (open resp. atmospheric dielectric barrier capillary discharge. Thin Solid Films 2006,
delimited) modifications on physical plasma and its antimicrobial effect 506:404.
against Pseudomonas aeruginosa and Staphylococcus aureus. GMS 60. Walsh JL, Shi JJ, Kong MG: Contrasting characteristics of pulsed and
Krankenhaushygiene Interdisziplinär 2012, 7(1):Doc02. doi:10.3205/dgkh000186. sinusoidal cold atmospheric plasma jets. Appl Phys Lett 2006, 88:171501.
35. Hong YF, Kang JG, Lee HY, Uhm HS, Moon E, Park YH: Sterilization effect of 61. Laroussi M: Sterilization of contaminated matter with an atmospheric
atmospheric plasma on Escherichia coli and Bacillus subtilis endospores. pressure plasma. IEEE Trans Plasma Sci 1996, 24:1188–1191.
Lett Appl Microbiol 2009, 48(1):33–37. 62. Ermolaeva SA, Sysolyatina EV, Kolkova NI, Bortsov P, Tuhvatulin AI, Vasiliev
36. Koinuma H, Ohkubo H, Hashimoto T, Inomata K, Shiraishi T, Miyanaga A, MM, Mukhachev AY, Petrov OF, Tetsuji S, Naroditsky BS, Morfill GE, Fortov
Hayashi S: Development and application of a microbeam plasma VE, Grigoriev AI, Zigangirova NA, Gintsburg AL: Non-thermal argon plasma
generator. Appl Phys Lett 1992, 60(7):816–817. is bactericidal for the intracellular bacterial pathogen Chlamydia
37. Inomata K, Ha H, Chaudhary KA, Koinuma H: Open air deposition of SiO2 trachomatis. J Med Microbiol 2012, 61:793–799.
film from a cold plasma torch of tetramethoxysilane‐H2‐Ar system. Appl 63. Klämpfl TG, Isbary G, Shimizu T, Li Y-F, Zimmermann JL, Stolz W, Schlegel J,
Phys Lett 1994, 64:46. Morfill GE, Schmidt H-U: Cold atmospheric air plasma sterilization against
38. Ha H, Inomata K, Koinuma H: Plasma chemical vapor deposition of SiO2 spores and other microorganisms of clinical interest. Appl Environ Micro-
on air-exposed surfaces by cold plasma torch. J Electrochem Soc 1995, biol 2012, 78(15):5077.
142(8):2726–2730. 64. Leclaire C, Lecoq E, Orial G, Clement F, Bousta F: Fungal decontamination by
39. Inomata K, Koinuma H, Oikawa Y, Shiraishi T: Open air photoresist ashing cold plasma : an innovating process for wood treatment. Braga (Portugal):
by a cold plasma torch: catalytic effect of cathode material. Appl Phys Lett COST Action IE0601 / ESWM - International Conference 5–7 November
1995, 66:2188. 2008; 2008.
40. Ha H, Yoshimoto M, Koinuma H, Moon BK, Ishiwara H: Open air plasma 65. Moreau S, Moisan M, Tabrizian M, Barbeau J, Pelletier J, Ricard A, Yahia L:
chemical vapor deposition of highly dielectric amorphous TiO2 films. Using the flowing afterglow of a plasma to inactivate Bacillus subtilis
Appl Phys Lett 1996, 68:2965. spores: Influence of the operating conditions. J Appl Phys 2000,
41. Ha H, Moon BK, Horiuchi T, Inushima T, Ishiwara H, Koinuma H: Structure 88:1166–1174.
and electric properties of TiO2 films prepared by cold plasma torch 66. Richardson JP, Dyer FF, Dobbs FC, Alexeff I, Laroussi M: Year. On the use of
under atmospheric pressure. Mater Sci Eng 1996, B41(1):143–147. the resistive barrier discharge to kill bacteria: Recent results. In 27th IEEE
42. Inomata K, Aoki N, Koinuma H: Jpn J Appl Phys 1994, 33:197. International Conference on Plasma Science - ICOPS2000. New Orleans(USA);
43. Lee B, Kusano Y, Kato N, Naito K, Horiuchi T, Koinuma H: Oxygen plasma 2000:109–109.
treatment of rubber surface by the atmospheric pressure cold plasma 67. Laroussi M, Leipold F: Evaluation of the roles of reactive species, heat,
torch. Jpn J Appl Phys 1997, 36(5A):2888–2891. and UV radiation in the inactivation of bacterial cells by air plasmas at
44. Stoffels E, Flikweert AJ, Stoffels WW, Kroesen GMW: Plasma needle: a atmospheric pressure. Int J Mass Spectrom 2004, 233:81–86.
non–destructive atmospheric plasma source for fine surface treatment 68. Fridman G, Friedman G, Gutsol A, Shekhter AB, Vasilets VN, Fridman A:
of (bio) materials. Plasma Sources Sci T 2002, 4:383–388. Applied plasma medicine. Plasma Processes Polym 2008, 5:503–533.
45. Kieft IE, Laan EPvd, Stoffels E: Electrical and optical characterization of the 69. Joshi SG, Cooper M, Yost A, Paff M, Ercan UK, Fridman G, Friedman G,
plasma needle. New J Phys 2004, 6:149. Fridman A, Brooks AD: Nonthermal dielectric-barrier discharge plasma-
46. Li S-Z, Huang W-T, Zhang J, Wang D: Optical diagnosis of an argon/oxy- induced inactivation involves oxidative dna damage and membrane
gen needle plasma generated at atmospheric pressure. Appl Phys Lett lipid peroxidation in Escherichia coli. Antimicrob Agents Chemother 2012,
2009, 94:111501. 56(4):2028–2036.
47. Govil S, Gupta V, Pradhan S: Plasma needle: the future of dentistry. Indian 70. Kelly-Wintenberg K, Hodge A, Montie TC, Deleanu L, Sherman D, Roth JR,
J Basic Appl Med Res 2012, 1(2):143–147. Tsai P, Wadsworth L: Use of a one atmosphere uniform glow discharge
48. Jiang C, Gundersen MA, Schaudinn C, Webster P, Jaramillo DE, Sedghizadeh plasma to kill a broad spectrum of microorganisms. J Vac Sci Technol A-
PP, Costerton JW: An atmospheric pressure non-thermal plasma needle Vacuum Surfaces and Films 1999, 17:1539–1544.
for endodontic biofilm disinfection. IEEE Int Confer Plasma Sci - ICOPS 71. Mendis DA, Rosenberg M, Azam F: A note on the possible electrostatic
2011:1–1. doi:10.1109/PLASMA.2011.5993048. disruption of bacteria. IEEE T Plasma Sci 2000, 28:1304–1306.
49. van den Bedem LJM, Sladek REJ, Steinbuch M, Stoffels Adamowicz E: 72. Laroussi M: Nonthermal decontamination of biological media by
Plasma treatment of S. mutans biofilms cultured in a simulated dental cavity atmospheric pressure plasmas: Review, analysis, and prospects. IEEE T
model. Eindhoven, the Netherlands: XXVIIth ICPIG; 2005. Plasma Sci 2002, 30:1409–1415.
50. Schaudinn C, Jaramillo D, Freire MO, Sedghizadeh PP, Nguyen A, Webster P, 73. Fridman G, Brooks AD, Balasubramanian M, Fridman A, Gutsol A, Vasilets VN,
Costerton JW, Jiang C: Evaluation of a nonthermal plasma needle to Ayan H, Friedman G: Comparison of direct and indirect effects of
eliminate ex vivo biofilms in root canals of extracted human teeth. Int nonthermal atmospheric-pressure plasma on bacteria. Plasma Processes
Endod J 2013, 46(10):1–8. Polym 2007, 4:370–375.
51. Sladek REJ, Filoche SK, Sissons CH, Stoffels E: Treatment of Streptococcus 74. Stoffels E, Sakiyama Y, Graves DB: Cold atmospheric plasma: charged
mutans biofilms with a nonthermal atmospheric plasma. Lett Appl species and their interactions with cells and tissues. IEEE Trans Plasma Sci
Microbiol 2007, 45(3):318–323. 2008, 36:1441–1457.
75. Munakata N, Hieda K, Kobayashi K, Ito A, Ito T: Action spectra in ultraviolet 100. Sung Kil K, Myeong Yeol C, Il Gyo K, Kim PY, Yoonsun K, Gon Jun K,
wavelengths (150–250 nm) for inactivation and mutagenesis of Bacillus Mohamed A-AH, Collins GJ, Jae Koo L: Reactive hydroxyl radical-driven
subtilis spores obtained with synchrotron radiation. Photochem Photobiol oral bacterial inactivation by radio frequency atmospheric plasma.
1986, 44:385–390. Appl. Phys. Lett 2011, 98(14):143702–143702–3.
76. Choi JH, Han I, Baik HK, Lee MH, Han DW, Park JC, Lee IS, Song KM, Lim YS: 101. Jiang CQ, Chen MT, Gorur A, Schaudinn C, Jaramillo DE, Costerton JW,
Analysis of sterilization effect by pulsed dielectric barrier discharge. Sedghizadeh PP, Vernier PT, Gundersen MA: Nanosecond Pulsed Plasma
J Electrostat 2006, 64:17–22. Dental Probe. Plasma Processes and Polymers 2009, 6:479–483.
77. Kelly-Wintenberg K, Montie TC, Brickman C, Roth JR, Carr AK, Sorge K, 102. Rupf S, Lehmann A, Hannig M, Schäfer B, Schubert A, Feldmann U,
Wadsworth LC, Tsai PPY: Room temperature sterilization of surfaces and Schindler A: Killing of adherent oral microbes by a non-thermal
fabrics with a One Atmosphere Uniform Glow Discharge Plasma. atmospheric plasma jet. J Med Microbiol 2010, 59:206–212.
J Ind Microbiol Biotechnol 1998, 20:69–74. 103. Lu XP, Cao YG, Yang P, Xiong Q, Xiong ZL, Xian YB, Pan Y: An RC Plasma
78. Birmingham JG: Mechanisms of bacterial spore deactivation using Device for Sterilization of Root Canal of Teeth. IEEE Transactions on
ambient pressure nonthermal discharges. IEEE T Plasma Sci 2004, Plasma Science 2009, 37:668–673.
32:1526–1531. 104. Li Y: Tooth bleaching using peroxide-containing agents: current status of
79. Kostov KG, Rocha V, Koga-Ito CY, Matos BM, Algatti MA, Honda RY, Kayama safety issues. Compend Contin Educ Dent 1998, 19(8):783–786. 788, 790,
ME, Mota RP: Bacterial sterilization by a dielectric barrier discharge (DBD) passim; quiz 796.
in air. Surf Coat Tech 2010, 204:2954–2959. 105. Kawamoto K, Tsujimoto Y: Effects of the hydroxyl radical and hydrogen
80. Trompeter FJ, Neff WJ, Franken O, Heise M, Neiger M, Liu SH, Pietsch GJ, peroxide on tooth bleaching. J Endod 2004, 30:45–50.
Saveljew AB: Reduction of Bacillus Subtilis and Aspergillus Niger spores 106. Lee HW, Kim GJ, Kim JM, Park JK, Lee JK, Kim GC: Tooth bleaching with
using nonthermal atmospheric gas discharges. IEEE T Plasma Sci 2002, nonthermal atmospheric pressure plasma. J. Endod. 2009, 35(4):587–591.
30:1416–1423. 107. Lee HW, Nam SH, Mohamed AH, Kim GC, Lee JK: Atmospheric Pressure
81. Heise M, Neff W, Franken O, Muranyi P, Wunderlich J: Sterilization of Plasma Jet Composed of Three Electrodes: Application to Tooth
polymer foils with dielectric barrier discharges at atmospheric pressure. Bleaching. Plasma Process. Polym. 2010, 7:274–280.
Plasmas Polym 2004, 9:23–33. 108. Sun P, Pan J, Tian Y, Bai N, Wu H, Wang L, Yu C, Wei S, Zhang J, Zhu W,
82. Park BJ, Lee DH, Park JC, Lee IS, Lee KY, Hyun SO, Chun MS, Chung KH: Fang J: Tooth-whitening with hydrogen peroxide assisted by a direct
Sterilization using a microwave-induced argon plasma system at atmos- current, cold, atmospheric-pressure air plasma microjet. IEEE Trans.
pheric pressure. Phys Plasmas 2003, 10:4539–4544. Plasma Sci. 2010, 38(8):1892–1896.
83. Lee KY, Park BJ, Lee DH, Lee IS, Hyun SO, Chung KH, Park JC: Sterilization of 109. Jie P, Peng S, Ye T, Haixia Z, Haiyan W, Na B, Fuxiang L, Weidong Z, Jue Z,
Escherichia coli and MRSA using microwave-induced argon plasma at Becker KH, Jing F: A Novel Method of Tooth Whitening Using Cold
atmospheric pressure. Surf Coat Tech 2005, 193:35–38. Plasma Microjet Driven by Direct Current in Atmospheric-Pressure Air.
84. Boudam MK, Moisan M, Saoudi B, Popovici C, Gherardi N, Massines F: IEEE TRANSACTIONS ON PLASMA SCIENCE 2010, 38(NO. 11):3143–3151.
Bacterial spore inactivation by atmospheric-pressure plasmas in the 110. Park JK, Nam SH, Kwon HC, Mohamed AAH, Lee JK, Kim GC: Feasibility of
presence or absence of UV photons as obtained with the same gas non thermal atmospheric pressure plasma for intracoronal bleaching.
mixture. J Phys D Appl Phys 2006, 39:3494. Int. Endod. J. 2011, 44:170.
85. Pennies E: A mouth full of microbes. Science 2005, 307:1899–1901. 111. Seoul Hee NAM, Hyun Woo LEE, Soo Hyun CHO, Jae Koo LEE, Young Chan
86. Gibbons RJ, Van Houte J: Dental caries. Annu Rev Med 1975, 26:121–136. JEON, Gyoo Cheon KIM: High-efficiency tooth bleaching using
87. Mosci F, Perito S, Bassa S, Capuano A, Marconi PF: The role of nonthermal atmospheric pressure plasma with low concentration of
Streptococcus mutans in human caries. Minerva Stomatol 1990, hydrogen peroxide. J Appl Oral Sci 2013, 21(3):265–270.
39(5):413–429. 112. Claiborne D, McCombs G, Lemaster M, Akman MA, Laroussi M: Low-
88. Yip HK, Samaranayake LP: Caries removal techniques and instrumentation: temperature atmospheric pressure plasma enhanced tooth whitening:
a review. Clin Oral Investig 1998, 2(4):148–154. the next-generation technology. Int J Dent Hygiene 2013. doi:10.1111/
89. Banerjee A, Watson TF, Kidd EA: Dentine caries excavation: a review of idh.12031.
current clinical techniques. Br Dent J 2000, 188(9):476–482. 113. Rupf S, Idlibi AN, Umanskaya N, Hannig M, Nothdurft F, Lehmann A,
90. Baysan A, Whiley RA, Lynch E: Antimicrobial effect of a novel ozone– Schindler A, Lv M, Spitzer W: Disinfection and removal of biofilms on
generating device on micro–organisms associated with primary root microstructured titanium by cold atmospheric plasma. Deutscher Ärzte-
carious lesions in vitro. Caries Res 2003, 34(6):498–501. Verlag 2012, 28(2):126–137.
91. Nagayoshi M, Fukuizumi T, Kitamura C, Yano J, Terashita M, Nishihara T: 114. Koban I, Holtfreter B, Hu¨bner N-O, Matthes R, Sietmann R, Kindel E,
Efficacy of ozone on survival and permeability of oral microorganisms. Weltmann K-D, Welk A, Kramer A, Kocher T: Antimicrobial efficacy of non-
Oral Microbiol Immun 2004, 19(4):240–246. thermal plasma in comparison to chlorhexidine against dental biofilms
92. Hems RS, Gulabivala K, Ng YL, Ready D, Spratt DA: An in vitro evaluation of on titanium discs in vitro – proof of principle experiment. J Clin Periodon-
the ability of ozone to kill a strain of Enterococcus faecalis. Int Endod J tol 2011, 38:956–965.
2005, 38:22–29. 115. Su-Jin S, Jung-Bo H, Mi-Jung Y, Chang BMW, Chang-Mo J, Young-Chan J:
93. Malmstrom HS, McCormack SM, Fried D, Featherstone JDB: Effect of CO2 Sterilization effect of atmospheric pressure non-thermal air plasma on
laser on pulpal temperature and surface morphology: an in vitro study. dental instruments. J Adv Prosthodont 2013, 5:2–8.
J Dent 2001, 29(8):521–529. 116. Ahmad Nour I, Fuad A-M, Matthias H, Antje L, Andre R, Axel S, Holger J,
94. Yoon G, Zabaznov M, Tsvetkov B, Kim S, Shcherbakov A: A compact 1.06/ Stefan R: Destruction of oral biofilms formed in situ on machined
1.32/2.94 mm pulsed laser for dentistry. Opt Laser Technol 2002, 34 titanium (Ti) surfaces by cold atmospheric plasma. Biofouling 2013,
(3):213–217. 29(No. 4):369–379.
95. Holmes J: Clinical reversal of root caries using ozone, double–blind, 117. Andy Charles R, Hao L, Qingsong Y, Changqi X, Xiaomei Y, Liang H, Yong W:
randomized, controlled 18–month trial. Gerontology 2003, 20(2):106–114. Dentin surface treatment using a non-thermal argon plasma brush for
96. Marsh PD: Dental plaque as a biofilm and a microbial community – interfacial bonding improvement in composite restoration. Eur J Oral Sci
implications for health and disease. BMC Oral Health 2006, 6(Suppl 1):S14. 2010, 118(5):510–516.
97. Goree J, Liu B, Drake D, Stoffels E: Killing of S-mutans bacteria using a 118. Yavirach P, Chaijareenont P, Boonyawan D, Pattamapun K, Tunma S,
plasma needle at atmospheric pressure. IEEE Transactions on Plasma Takahashi H, Arksornnukit M: Effects of plasma treatment on the shear
Science 2006, 34:1317–1324. bond strength between fiber reinforced composite posts and resin
98. Morris AD, McCombs GB, Akan T, Hynes W, Laroussi M, Tolle SL: Cold Plasma composite for core build-up. Dental Materials Journal 2009, 28(6):686–692.
Technology: Bactericidal Effects on Geobacillus Stearothermophilus and 119. Stoffels E: Plasma needle: Treatment of living cells and tissues, in Proc. San
Bacillus Cereus Microorganisms. J Dent Hygiene 2009, 83(2):55–61. Francisco, CA: Gaseous Electron. Conf; 2003:16.
99. Bo Y, Jierong C, Qingsong Y, Hao L, Mengshi L, Azlin M, Liang H, Yong W: 120. Yonson S, Coulombe S, Leveille V, Leask R: Cell treatment and surface
Oral bacteria deactivation using a low-temperature atmospheric argon functionalization using a miniature atmospheric pressure glow discharge
plasma brush. J Dent 2011, 39:48–56. plasma torch. J.Phys. D, Appl. Phys 2006, 39(16):3508–3513.
121. Shashurin A, Keidar M, Bronnikov S, Jurjus RA, Stepp M: Living tissue under 145. Bomi G, Mina K, Dan Bee K, Daeyeon K, Hyeonyu K, et al: Differential
treatment of cold atmospheric jet. Appl. Phys. Lett 2008, 93(no. 18):181–501. responses of human liver cancer and normal cells to atmospheric
122. Kieft IE, Kurdi M, Stoffels E: Reattachment and apoptosis after plasma- pressure plasma. APPLIED PHYSICS LETTERS 2011, 99:063701.
needle treatment of cultured cells. IEEE Trans. Plasma Sci. 2006, 146. Georgescu N, Lupu AR: Tumoral and normal cells treatment with
34(4):1331–1336. high-voltage pulsed cold atmospheric plasma jets. Plasma Science,
123. Kieft IE, Darios D, Roks AJM, Stoffels E: Plasma treatment of mammalian IEEE Trans 2010, 38:1949–55.
vascular cells: a quantitative description. IEEE Trans Plasma Sci 2005, 147. Panngom K, Baik KY, Nam MK, Han JH, Rhim H, Choi EH: Preferential killing
33:771–5. of human lung cancer cell lines with mitochondrial dysfunction by
124. Olga V, Mary Ann S, Michael K: ntegrin activation by a cold atmospheric nonthermal dielectric barrier discharge plasma. Cell Death Dis 2013,
plasma jet. New Journal of Physics 2012, 14(16pp):053019. 4(5):e642.
125. Lehnert BE, Iyer R: Exposure to low-level chemicals and ionizing radiation: 148. Tuhvatulin AI, Sysolyatina EV, Scheblyakov DV, DYu L, Vasiliev MM, Yurova
reactive oxygen species and cellular pathways. Hum Exp Toxicol 2002, MA, Danilova MA, Petrov OF, Naroditsky BS, Morfill GE, Grigoriev AI, Fortov
21:65–9. VE, Gintsburg AL, Ermolaeva SA: Non-thermal Plasma Causes p53-
126. Sensenig R, Kalghatgi S, Cerchar E, et al: Non-thermal plasma induces Dependent Apoptosis in Human Colon Carcinoma Cells. Acta Naturae
apoptosis in melanoma cells via production of intracellular reactive 2012, 4(3):82–87.
oxygen species. Ann Biomed Eng 2011, 39:674–87. 149. Yan X, Zou F, Zhao S, Lu X, He G, Xiong Z, Xiong Q, Zhao Q, Deng P, Hunag
127. Sun Ja K, Chung TH, Bae SH, Leem SH: Induction of apoptosis in human J, Yang G: On the mechanism of plasma inducing cell apoptosis. IEEE
breast cancer cells by a pulsed atmospheric pressure plasma jet. Trans Plasma Sci 2010.
Appl. Phys. Lett 2010, 97:023702. 150. Vandamme M, Robert E, Lerondel S, Sarron V, Ries D, Dozias S, Sobilo J,
128. Thiyagarajan M, Waldbeser L, Whitmill A: THP-1 leukemia cancer treatment Gosset D, Kieda C, Legrain B, Pape J-MPAL: ROS implication in a new
using a portable plasma device. Stud Health Technol Inform. 2012, antitumor strategy based on non-thermal plasma. Int. J. Cancer 2012,
173:515–7. 130:2185–2194.
129. Lars Ivo P, Katja E, Jan H, Friderike D, Lars N, Stephan D, Frank-Ulrich W, 151. Hak Jun A, Kang Il K, Geunyoung K, Eunpyo M, Sang Sik Y, Jong-Soo L:
Matthias E, Nils Olaf H, Cristin G, Claus Dieter H, Axel K, René B, Klaus-Dieter Atmospheric-Pressure Plasma Jet Induces Apoptosis Involving
W, Onur P, Claudia B, von Wolfram B: Tissue Tolerable Plasma (TTP) Mitochondria via Generation of Free Radicals. PLoS ONE 2011,
induces apoptosis in pancreatic cancer cells in vitro and in vivo. 6(11):e28154. doi:10.1371/journal.pone.0028154.
Partecke et al. BMC Cancer 2012, 12:473. 152. Xu Y, Zilan X, Fei Z, Shasha Z, Xinpei L, Guangxiao Y, Guangyuan H, Ostrikov
130. Walk RM, Snyder JA, Srinivasan P, Kirsch J, Diaz SO, Blanco FC, Shashurin A, K (K): Plasma-Induced Death of HepG2 Cancer Cells: Intracellular Effects
Keidar M, Sandler AD: Cold atmospheric plasma for the ablative of Reactive Species, Plasma Process. Polym 2012, 9:59–66.
treatment of neuroblastoma. J Pediatr Surg 2013, 48:67–73. 153. Rodríguez-Lozano FJ, Insausti CL, Iniesta F, Blanquer M, Ramírez MD,
131. Nagendra K, Kaushik, Yong Hee K, Yong Gyu H, Eun Ha C: Effect of jet Meseguer L, Meseguer-Henarejos AB, Marín N, Martínez S, Moraleda JM:
plasma on T98G human brain cancer cells. Current Applied Physics 2012. Mesenchymal dental stem cells in regenerative dentistry. Med Oral Patol
132. Köritzer J, Boxhammer V, Schäfer A, Shimizu T, Klämpfl TG, Li Y-F, Welz C, Oral Cir Bucal 2012, 17(6):e1062–e1067.
Schwenk-Zieger S, Morfill GE, Zimmermann JL, Schlegel J: Restoration of
Sensitivity in Chemo — Resistant Glioma Cells by Cold Atmospheric doi:10.1186/2045-9912-3-21
Plasma. PLoS ONE 2013, 8(5):e64498. Cite this article as: Hoffmann et al.: Cold Atmospheric Plasma: methods
133. Barekzi N, Laroussi M: Dose-dependent killing of leukemia cells by low- of production and application in dentistry and oncology. Medical Gas
temperature plasma. J. Phys. D: Appl. Phys 2012, 45:6pp. Research 2013 3:21.
134. Chul-Ho K, Seyeoul K, Jae Hoon B, Keunho L, Seung Ik J, Rack PD, Seung
Joon B: Effects of atmospheric nonthermal plasma on invasion of
colorectal cancer cells. APPLIED PHYSICS LETTERS 2010, 96:243701.
135. Arndt S, Wacker E, Li Y-F, Shimizu T, Thomas HM, Morfill GE, Karrer S,
Zimmermann JL, Bosserhoff A-K: Cold atmospheric plasma, a new strategy
to induce senescence in melanoma cells. Experimental Dermatology 2013,
22:284–289.
136. Kim CH, Bahn JH, Lee SH, et al: Induction of cell growth arrest by
atmospheric non thermal plasma in colorectal cancer cells. J Biotechnol
2010, 150(4):530–538.
137. Kim JY, Wei Y, Li J, et al: Single-cell-level microplasma cancer therapy.
Small 2011, 7:2291–5.
138. Vandamme M, Robert E, Pesnel S, et al: Antitumor effect of plasma
treatment on U87 glioma xenografts: preliminary results. Plasma
Processes Polym 2010, 7:264–73.
139. Keidar M, Walk R, Shashurin A, Srinivasan P, Sandler A, Dasgupta S, Ravi R,
Guerrero-Preston R, Trink B: Cold plasma selectivity and the possibility of
a paradigm shift in cancer therapy. Br J Cancer 2011, 105:1295–1301.
140. Kim GC, Kim GJ, Park S, Jeon S, Seo H, Iza F, Lee J: Air plasma coupled with
antibody-conjugated nanoparticles: a new weapon against cancer. Submit your next manuscript to BioMed Central
J. Phys. D: Appl. Phys 2009, 42(No 3):032005. 5pp. and take full advantage of:
141. Gan Young P, Myoung Soo K, June Ho B, Kyong Tai K, Gyoo Cheon K, Jae
Koo L: Biomedical Applications of Low Temperature Atmospheric
• Convenient online submission
Pressure Plasmas to Cancerous Cell Treatment and Tooth Bleaching.
Jpn. J. Appl. Phys 2011, 50:7. 08JF01. • Thorough peer review
142. Volotskova O, Hawley TS, Stepp MA, Keidar M: Targeting the cancer cell • No space constraints or color ﬁgure charges
cycle by cold atmospheric plasma. Sci. Rep. 2012, 2:636.
• Immediate publication on acceptance
143. Jae Young K, John B, Paul F, Thomas H, Yanzhang W, Jinhua L, Sung-O K:
Apoptosis of lung carcinoma cells induced by a flexible optical fiber- • Inclusion in PubMed, CAS, Scopus and Google Scholar
based cold microplasma. Biosensors and Bioelectronics 2011, 28:333–338. • Research which is freely available for redistribution
144. Jae Young K, John B, Paul F, Thomas H, Yanzhang W, Jinhua L, Sung-O K:
Single Cellular and Endoscopic Micro-plasma Cancer Therapy, Small.
2011, 7(16):2290. Submit your manuscript at
www.biomedcentral.com/submit

Cold Plasmas

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Hoffmann et al.

Medical Gas Research 2013, 3:21

REVIEW Open Access

Cold Atmospheric Plasma: methods of production

Introduction detachment, and cause death in cancer cells, researchers

required like in dentistry [47-52]. It has also been used

Pulsed direct current-driven plasma jets

necrotic, infected, and demineralized tissue is removed CAP + saline [110]

Use of CAP on oral pathogens

Table 1 In vitro and in vivo studies performed in Oncology with CAP

You might also like

Cold Plasmas

Uploaded by

Copyright:

Available Formats

Cold Plasmas

Uploaded by

Document Information

Copyright

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Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

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Cold Plasmas

Uploaded by

Copyright:

Available Formats

Hoffmann et al.

Medical Gas Research 2013, 3:21

REVIEW Open Access

Cold Atmospheric Plasma: methods of production

Introduction detachment, and cause death in cancer cells, researchers

required like in dentistry [47-52]. It has also been used

Pulsed direct current-driven plasma jets

necrotic, infected, and demineralized tissue is removed  CAP + saline [110]

Use of CAP on oral pathogens

Table 1 In vitro and in vivo studies performed in Oncology with CAP

You might also like

necrotic, infected, and demineralized tissue is removed CAP + saline [110]