900-mhz nonthermal atmospheric pressure plasma jet for biomedical applications

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258

900-MHz Nonthermal Atmospheric PressurePlasma Jet for Biomedical Applications

Jun Choi, Abdel-Aleam H. Mohamed, Sung Kil Kang, Kyung Chul Woo,Kyong Tai Kim, Jae Koo Lee*

A portable microwave-excited atmospheric pressure plasma jet (APPJ) using a coaxial trans-mission line resonator is introduced for applications of plasma biomedicine. Its unique featureincludes the portability andno need formatching network and cooling systemwith high powerefficiency, operating at 900MHzwith low ignitionpower less than 2.5W in argon at atmosphericpressure. The temperature at the downstream ofthe APPJ stays less than 47 8C (�320K) during5min of continuous operation. The optical emis-sion spectrum of the APPJ shows various reactiveradicals such as OH, NO, and O which are respon-sible for biomedicine. The APPJ was applied toinvestigate the acceleration of blood coagulation,which occurredwithin 20 s of plasma treatment invitro andwithin 1min in vivo. This is significantlyfaster than the natural coagulation.

Introduction

Nonthermal atmospheric pressure plasma sources are in

great demand for biomedical applications including cancer

cell treatment,[1] sterilization,[2] and coagulation.[3] Ideally,

the plasma generated should have low power and low gas

temperature. Furthermore, plasma sources should operate

at atmospheric pressure, have low cost and a long

operational life. Diverse plasma devices with different

J. K. Lee, J. Choi, A.-A. H. Mohamed, S. K. KangDepartment of Electronic and Electrical Engineering, PohangUniversity of Science and Technology, Pohang 790-784, Republicof KoreaFax: (þ82) 54 279 2903; E-mail: [email protected]. H. MohamedDepartment of Physics, Faculty of Science, Taibah University,Almadinah Almunawwarah, Saudi ArabiaDepartment of Physics, Faculty of Science, Beni-Suef University,Beni-Suef, EgyptK. C. Woo, K. T. KimDepartment of Life Science, Pohang University of Science andTechnology, Pohang 790-784, Republic of Korea

Plasma Process. Polym. 2010, 7, 258–263

� 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

power sources and electrode configurations have been

presented that partially fulfill these conditions.[4] The

plasma sources can be operatedwithDC,[5,6] low-frequency

(kHz),[7] RF,[8,9] microwave,[10,11] and pulsed power.[12]

Microwave-excited plasmas at atmospheric pressure

havebeendeveloped for surfacemodification,[11] analytical

purposes,[13] and biomedical applications including ster-

ilization[14] and detoxification.[15,16] These plasmas are

useful because the energy of the ions that strike the

electrodes in the high-frequency devices is very low due to

the collisionality of the sheath[17–19] and the low sheath

potential that develops at microwave frequency.[20] In

addition, the size of the device can be reduced as the

microwave operating frequency increases. For operating

frequencies of 900MHz and 2.45GHz, a number of low-cost

power modules and solid-state components are available

because they have been developed for mobile communica-

tions systems. Thus microwave-excited microplasmas

operating at low power may meet the need for long-

lifetime devices capable of operating at atmospheric

pressure.[10]

In this study, we propose a portable, matching-network-

free microwave-excited atmospheric pressure plasma jet

DOI: 10.1002/ppap.200900079

900-MHz Nonthermal Atmospheric Pressure Plasma . . .

(APPJ) based on a coaxial transmission line resonator (CTLR)

and show a potential use of biomedical applications.

Experimental Part

Configuration of Device

The device has been designed to minimize power losses and

maximize the power efficiency based on an analytic model and

finite elementmethod (FEM) simulation.We reported the electrical

characteristics of thedevice in detail in thepreviouswork.[21] In the

device (Figure 1), the resonator consists of a quarter wavelength of

coaxial line (characteristic impedance¼50V) connected tothe feed

power by a subminiature type A (SMA) connector (Figure 1a). One

endof thecoaxial line iselectricallyopen (Figure1b)andtheother is

short-circuited to resonate at the exciting frequency. Therefore, at

resonance, the current is zero and the voltage is maximal at the

open end where the plasma is discharged. A metal tip is used to

reduce thegapdistance to40mmand toenhance theelectricfield to

ignite the plasma.

Theoverall lengthof thedevice is83mm,which isone-quarterof

the wavelength of 900-MHz radiation. At resonance, the input

impedance of the CTLR is real and its value depends on the location

of the power feed as Equation (1):

Fig(a)

Plasma

� 2010

Zin � 4Z0 sin bl1ð Þal

V (1)

where Zin is the input impedance of the resonator, Z0 the

characteristic impedance of the coaxial transmission line, l the
1
length fromfeedingpoint to shortport, j the complexnumberffiffiffiffiffiffiffi�1

p,

l the wavelength for the given frequency and dielectric constant

(er¼ 1 for air), a the attenuation constant, and b¼ 2p/l is the phaseconstant of the coaxial line, i.e., k¼ b – ja the complex propagation

constant or wave number. Accordingly, the CTLR is powered at a

point by an SMA connector where the input impedance to the

device is 50V. This eliminates the need formatchingnetworks and

the power losses that they cause.

Air was used as a dielectric of the coaxial line to make the

working gas flow through the device through two gas holes at the

short end of the device. This use of air as a dielectric for the coaxial

line reduces power loss and improves the power efficiency of the

CTLR.Consequently, theCTLR is capableof self-ignitingbelow2.5W

ure 1. The configuration of the CTLR operating at 900MHzside view (b) front view (c) nonthermal microwave-excited APPJ.

Process. Polym. 2010, 7, 258–263

WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

input power[21] in argonunder awide range of pressures, including

atmosphericpressure.The lengthof theAPPJ canbevaried from5to

15mm (Figure 1c) depending on the gas flow rate and input power.

Experimental Setup

A signal generator (Agilent N5181A) and a microwave power

amplifier (AR 60S1G3) were used to supply power to the CTLR

(Figure 2). The forward and reflected powers were measured

simultaneously using two directional couplers (Narda 3202B-20),

two sets of power sensors (Agilent N1921A, HP 8482A), and power

meters (Agilent N1911A, HP EPM-441A). In this experiment, we

used a commercial signal source and a large size of a microwave

power amplifier. However, a compact power amplificationmodule

includingdirectional couplersandpowersensors isquite feasible to

manufacture and we are developing it on a printed circuit board

and eventually on a chip for the hand-held plasma sourceworking

on microwave power.

The emission spectrum of the APPJ was characterized by optical

emission spectroscopy, using a 750mm focal length scanning

monochromator (Dong Woo Optron Monora 700i) equipped with a

built-in high-sensitivity photomultiplier tube (PMT, Hamamatsu

R928) with a 2400gr �mm�1 grating blazed at 240nm. The

monochromator collects light using an optical fiber. In this work,

thefiberwasorientedperpendicular to the longaxisofAPPJ,with its

tip2mmfromtheAPPJ.Duringall spectroscopicmeasurements, the

discharge was operating at atmospheric pressure using argon flow

in ambient air.

Blood samples from a mouse (CBA/N strain) were used to

investigate coagulationbydirect and indirect contactwith theAPPJ.

A10ml of bloodwasplacedonaslideglassand treated invitrobythe

plasmaover9mmdistancefromthenozzleofCTLR.A tail-cutmouse

was applied to evaluate the blood coagulation in vivo by the APPJ.

Results and Discussion

HFSS Simulation and Description of AtmosphericPressure Plasma Jet (APPJ)

To investigate the electric field (E-field) distribution at the

open end of the device before the plasma ignites, a

simulation based on the FEM was performed using a

commercial package (Ansoft HFSS). The HFSS simulation

(Figure3) showsthatattaching themetal tipat theopenend

of the CTLR increases the E-field to 5� 106V �m�1 for 1W

Figure 2. Experimental setup for the APPJ based on the CTLR.

www.plasma-polymers.org 259

J. Choi, A.-A. H. Mohamed, S. K. Kang, K. C. Woo, K. T. Kim, J. K. Lee

Figure 3. HFSS simulation of the CTLR with 40mm gap distanceand 1W input power (a) E-field distribution in the direction offront view (Figure 1b) (b) E-field radiation in the direction of sideview (Figure 1a) at the open end of the device before plasmaignition. (The inset is a magnification of E-field for each figure).

a)

260

input power (Figure 1b and 3a). The CTLR can ignite the

argon plasma with the auxiliary tip using less than 3W

input power at atmospheric pressure. Inserting the metal

tip to theCTLRdidnotcauseanysignificantperturbation for

the overall electromagnetic behavior of the resonator such

as a shift of resonant frequency. The E-field is radiated only

fromtheopenendof thedeviceanddecreases to zerowithin

5mm (Figure 3b). This confinement of the E-field prevents

unwanted electromagnetic interference and allows the

array of the device to enlarge the plasma treatment area.

Once the plasmawas ignited, themetal tipwas removed

from the CTLR. Figure 4(a) shows the APPJs by the CTLR

Figure 4. Microwave-excited APPJs and temperature measure-ment (a) argon APPJ pictures in ambient air by the CTLR with3W as a function of gas flow rate (b) temperature at the down-stream of the APPJ at 5 slm gas flow and 3W input power for5min of continuous measurement.



without the tip at 3W input power and gas flow ranged

from 2 to 10 slm. The average length of the APPJ (Lp) was

9.14mm in the given condition. The APPJ showed stable

operationup to 6 slm (cross-sectional area of thenozzlewas

125.6mm2 and effective gas flow speedwas 0.8m � s�1) gas

flow rate and changed to turbulent-like mode for higher

flow rate than 6 slm. The Lp was maximal at 6 slm and

getting shorter as the gas flow increased. Figure 4(b)

presents the measured temperature of the downstream of

the APPJ (�9mm from the nozzle) at 3W input power and

5 slm (0.66m � s�1 of effective gas flow speed), which is a

stable operation condition of the APPJ. The temperature

was measured by a fiber optic sensor (FISO FTI-10). As a

result of continuous measurement for 5min, the gas

temperature of the APPJ did not exceed 47 8C (�320K).

Analysis of Optical Emission Spectrum

The rotational temperature of theAPPJwas estimated from

the OH (A2Sþ!X2P), v(0–0) band using LIFBASE[22]

(Figure 5). The discharge is far from equilibrium and the

rotational temperature of OHmolecules in the discharge is

b)

Figure 5. Gas temperature of the APPJ (a) optical emission spec-trum of OH band of the CTLR with 1.5W input power and 6 slmargon gas flow rate at atmospheric pressure compared withLIFBASE calculations of OH band for 450 and 550K (b) dependenceof the gas temperature on the microwave input power at atmos-pheric pressure.

DOI: 10.1002/ppap.200900079


Figure 7. NO radical emission of the microwave-excited APPJ at8 slm argon flow and 3W input power.

�450–550Kwhen input power is 1.5Wand gas flow rate is

6 slm (Figure 5a). This temperature decreases with increase

in distance from the CTLR open end and no thermal effect

was observed in the downstream of the APPJ (Figure 1c). At

6 slm, the gas temperature increases linearly from 500K at

1.5W to 620K at 3.5W (Figure 5b) due to gas heating as the

input power to the APPJ increases (i.e., the difference

between the forward and reflected power). These results

are consistent with observations in other high pressure

plasmas.[23] The dominant gas heating mechanism in

microwave-excited argon microplasma at atmospheric

pressure is the elastic collisions between electrons and

atoms,[24] so the observed heating is probably a conse-

quence of the increase in electron density.[25] Above 3.5W,

the gas temperature stabilized, which agrees with results

reported for air plasma[26] and could result from the

enlargement of the plasma dimension as a function of

increasing input power.

Figure 6 shows the optical emission spectra from 200 to

900nm. Because the argon APPJ was flushed into the

ambient air, argon lines dominate the 700–900nm and the

energetic charged particles and excited argon species can

stimulate the ground-state oxygen molecules. As a result,

b)

a)

Figure 6. Optical emission spectra of the microwave-excited APPJat 2mm from the nozzle with 4W input power and 8 slm argongas flow rate (a) 200–600nm and (b) 600–900nm.



they present strong emission lines of argon species as well

as highly reactive species such as nitrogen species (230–

280nm) andOH radicals (309nm) in Figure 6(a) and atomic

oxygen lines (777.4 nm) in Figure 6(b). Emission bands

corresponding to nitric oxide (NO) were observed in the

emission spectra (Figure 7) of the APPJ. The NO radical of

nonthermalatmosphericpressureplasmacanhelpregulate

blood coagulation and accelerate wound treatment.[27]

Thehighgas temperatureat the ignitionpointof theAPPJ

is likely to contribute the NO formation[28,29] and the APPJ

cools down at the afterglow due to the flow ofworking gas.

Themechanism of NO production in nonthermal plasma is

controlledby reactionsofatomicnitrogenwithO2andO3as

follows.[30]

Nþ O2 ! NOþ O (2)

Nþ O3 ! NOþ O2 (3)

Toaccelerate (2) and (3), thenitrogenmolecules shouldbe

dissociated to atomic nitrogen by the impact of electrons. A

recent computational work shows that the microwave

discharge can generate high population of energetic

electrons.[20] This presents the microwave-exited plasma

has high possibility to produce atomic nitrogen and NO

abundantly. In addition, the NO generation is favored by

the gas temperature by the following equation:

k ¼ 1:5� 10�11 exp � 3 600

Tg

� �cm3 �mol�1 � s�1 (4)

where k is the rate coefficient of the reactions and Tg is the

gas temperature.[31] As Equation (4), it is noted that

the reaction rate constant is dependent on the gas

temperature. The NO production, therefore, increases with


J. Choi, A.-A. H. Mohamed, S. K. Kang, K. C. Woo, K. T. Kim, J. K. Lee

262

increase in the gas temperature at the ignition point of the

APPJ. The NO radical has multiple biological functions:

regulation of blood vessel tone, blood coagulation,

immune system and early apoptosis, etc.[29] Furthermore,

NO shows anti-microbial effect and strong sterilization

activity of bacteria.[14] It is suggested that the microwave-

excited discharge presented could be a good candidate for

biomedical applications, particularly inflammation

remedy, healing of wound surface, and stimulation of

regenerative processes.

Blood Coagulation

We investigated whether the APPJ could accelerate blood

coagulation, both in vitro and in vivo. Blood samples were

collected from a healthy mouse (CBA/N strain). The blood

was treated with ethylene diamine tetra-acetic acid in the

concentration of 5mmol � l�1which is an anti-coagulant for

inhibiting fast blood coagulation naturally in the air. To

quantify in vitro coagulation rates, a 10-ml sample of this

bloodwas placed on a slide glass (Figure 8a–c) and the APPJ

was applied to the blood at 3W input power and 3 slm gas

flow rate. Measurements were replicated at least three

times for each sample. Untreated blood did not coagulate

during the measurements (Figure 8a). The blood started to

coagulate after 10 s of plasma treatment (Figure 8b) and

was completely coagulated after 20 s of treatment

(Figure 8c). This result is comparable to a previous report[27]

and the role of atmospheric nonthermal plasma in

blood coagulation was studied by Kalghatgi et al.[3]

To investigate the effect of gas flow, same 10-ml blood

samples were treated by argon gas at 3 slm for 10 and 20 s.

Although coagulation was observed in the test, the effect

Figure 8. In vitro and in vivo blood coagulation using APPJ at 3.5Winput power and 3 slm argon flow rate: (a) control; (b) aftertreatment for 10 s; (c) after treatment for 20 s [10ml anti-coagu-lated blood was used for (a–c)]; (d) side-view (noncontact) of invitro blood coagulation after treatment for 30 s; (e) in vivocoagulation of bleeding for living mouse.



was minor. Indirect coagulation was also observed

(Figure 8d) after 30 s of treatment when the APPJ was held

3mm away from the blood sample. Even though the APPJ

didnot contact theblooddirectly, coagulationoccurred. The

noncontact coagulation may result from various radicals

generated from the APPJ and minor thermal effect. In fact,

the gas temperature of the APPJ did not exceed 38.3 8C on

average during 20 s treatmentwhich is slightly higher than

the human body temperature (Figure 4b).

To quantify the effect of plasma application on coagula-

tion in vivo, the mouse was anesthetized and the tail was

cut to inducebleeding (Figure 8e). At first,we left the cut tail

without any treatment. The bleeding stopped naturally

within 5–6min. When the APPJ was applied, the blood

started to coagulate at once and changed toa clotwith time.

Furthermore, this clot closed the wound and reduced the

amount of bleeding. The bleeding usually stopped within

1min with the plasma treatment. This work shows the

potential of the microwave-excited APPJ as a medical

method for rapid and thermally safe coagulation.

Conclusion

In summary, we have developed a portable microwave-

excitedAPPJ that uses a coaxial transmission line resonator

operating at 900MHz with low power. HFSS simulation

based on FEM demonstrated that the E-field distribution at

the open end of the CTLR was �106V �m�1 and that the

metal tip caused no significant perturbation. The APPJ

shows highly reactive species including OH, NO, and O

radicals. The emission spectrumof theOHbandwasused to

determine the gas temperature of an APPJ using argon in

ambient air. The APPJ was clearly nonthermal and the

gas temperature increased from 500 to 620K for given

input power. In in vitro tests tomeasurewhether using the

APPJ accelerates blood coagulation significantly, this

process began after 10 s of treatment and was completed

within 20 s. In vivo blood coagulation was observed after

less than 1min of plasma treatment. These results indicate

that this APPJ has potential possibility for biomedical

applications including coagulation, wound healing, and

sterilization.

Acknowledgements: The authors are grateful to Top EngineeringCo. for lending their microwave power amplifier for theexperiment. This work was supported by the Korea Science andEngineering Foundation (KOSEF) grant funded by the Koreagovernment (MOST) (no. R01-2007-000-10730-0), and the KoreaMinistry of Education, Science, and Technology through its BrainKorea 21 program.

Received: July 6, 2009; Revised: November 10, 2009; Accepted:November 18, 2009; DOI: 10.1002/ppap.200900079

DOI: 10.1002/ppap.200900079


Keywords: atmospheric pressure plasma jet (APPJ); blood coagu-lation; microwave discharges; nonthermal plasma; plasmatreatment

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900-mhz nonthermal atmospheric pressure plasma jet for biomedical applications

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