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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

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Front. Chem. Sci. Eng.    2019, Vol. 13 Issue (2) : 238-252    https://doi.org/10.1007/s11705-019-1801-8
REVIEW ARTICLE
Important parameters in plasma jets for the production of RONS in liquids for plasma medicine: A brief review
Anna Khlyustova1,2, Cédric Labay1,2, Zdenko Machala3, Maria-Pau Ginebra1,2, Cristina Canal1,2()
1. Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Universitat Politècnica de Catalunya, Barcelona 08019, Spain
2. Research centre in Multiscale Science and Engineering, Universitat Politècnica de Catalunya, Barcelona 08019, Spain
3. Faculty of Mathematics, Physics and Informatics, Comenius University, Bratislava 84248, Slovakia
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Abstract

Reactive oxygen and nitrogen species (RONS) are among the key factors in plasma medicine. They are generated by atmospheric plasmas in biological fluids, living tissues and in a variety of liquids. This ability of plasmas to create a delicate mix of RONS in liquids has been used to design remote or indirect treatments for oncological therapy by treating biological fluids by plasmas and putting them in contact with the tumour. Documented effects include selective cancer cell toxicity, even though the exact mechanisms involved are still under investigation. However, the “right” dose for suitable therapeutical activity is crucial and still under debate. The wide variety of plasma sources hampers comparisons. This review focuses on atmospheric pressure plasma jets as the most studied plasma devices in plasma medicine and compiles the conditions employed to generate RONS in relevant liquids and the concentration ranges obtained. The concentrations of H2O2, NO2−, NO3− and short-lived oxygen species are compared critically to provide a useful overview for the reader.
Keywords atmospheric plasma jets      liquids      ROS      RNS      plasma-dose     
Corresponding Author(s): Cristina Canal   
Online First Date: 29 April 2019    Issue Date: 22 May 2019
 Cite this article:   
Anna Khlyustova,Cédric Labay,Zdenko Machala, et al. Important parameters in plasma jets for the production of RONS in liquids for plasma medicine: A brief review[J]. Front. Chem. Sci. Eng., 2019, 13(2): 238-252.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-019-1801-8
https://academic.hep.com.cn/fcse/EN/Y2019/V13/I2/238
Fig.1  Representative picture of three examples of plasma jets of interest in plasma medicine: (a) atmospheric pressure argon plasma jet (kINPen), (b) plasma needle, and (c) microplasma COST
Fig.2  Overview of the short- and long-lived RONS generated in liquid media by APPJ with detail of the liquid media in which each species has been quantified in literature and the corresponding detection methods employed therein
Gas Flow rate/ (L?min−1) Conditions t/s V/mL Liquid [H2O2] /(µmol?L−1) Ref.
He 0.05 U = 8 kV, f = 20 kHz,
d = 10 mm		 240 500 PBS (Ca2+/Mg2+) 1300a) [28]
0.1 U = 8 kV, f = 15 kHz,
P = 5 W		 120 100 DMEM+FBS 14b) [29]
DI water 26b)
1 U = 7 kV, f = 10 kHz 300 4000 DI water 18b) [30]
1.67 U = 7.5 kV, f = 10 kHz, d = 2 mm, shielding gas O2/N2 600 2000 PBS 265b) [31]
2 U = 18 kV, f = 24.9 kHz, d = 10 mm 60 100 Aqueous solutions 50?80a) [32]
3 U = 10 kV, f = 9.69 kHz 150 100 DI water 1750a) [33]
DMEM 1600a)
DMEM+ 10% FCS 1600a)
4.7 U = 3.16 kV, d = 30 mm 60 or
120		 1000 DMEM 35c) [34]
PBS 42c)
5 U = 5?9 kV, f = 5 kHz, d = 25 mm 60 500 MEM 30c) [35]
5 U = 2 kV, P = 6 W,
d = 20 mm		 1800 4000 McCoy 1470.6d) [36]
advDMEM 2117.6d)
He+O2 2 U = 15 kV, f = 1 kHz,
d = 5 mm		 300
600
900		 360 PBS 174c)
391c)
1250c)		 [37]
8 U = 28 kV, f = 2 kHz 60 300 Phenol-free RPMI 1640 6c) [38]
Ar 1 U = 9 kV, f = 16 kHz,
d = 9 mm		 60 100 PBS 88.2c) [39]
2 U = 7 kV, f = 60 Hz,
d = 13 mm		 300 3000 DMEM+P/S+FBS 110c) [40]
DMEM 92c)
2 U = 10 kV, f = 60 Hz,
d =3 mm		 120 8000 Ringer’s saline 8c) [41]
3 U = 0.7 kV, I = 3 mA,
f = 16 kHz, P = 0.2 W		 1800 DI water 800a) [42]
3 U = 7 kV, f = 10 kHz,
d = 15, 25 and 80 mm		 300 4000 DI water d = 15 mm, 16b) [43]
d = 11 mm, 80b)
d = 25 mm, 3.7b)
Other gases 1, O2 U = 9 kV, f =16 kHz,
d = 9 mm		 60 100 PBS 1559c) [39]
1, N2 PBS 735c)
1, CO2 PBS 1265c)
1, air PBS 58.8c)
Ar, RF plasma jet 1.5 F = 13.7 MHz,
d = 5?13 mm		 60 3000 PBS (Ca2+/Mg2+)+
1 g?L–1 D-glucose		 15?250c) [44]
Ar, kINPen 3 U = 2?6 kV, f = 1.1 MHz, d = 5 mm 60 1000 Phenol-free RPMI 1640 60c) [45]
3 U = 2?6 kV, f = 1 MHz, d = 9 mm 100 5000 RPMI 1640+8% FCS+1% P/S 45?210d) [46]
3 U = 2?6 kV, f = 1 MHz 180 5000 Phenol-free RPMI 1640 100c) [47]
3 U = 2?6 kV, f = 1 MHz 180 NaCl 78d) [48]
3 DPBS 60d)
3 RPMI 1640 88d)
3 U = 2?6 kV, f = 1 MHz, d = 10 mm 300 2000 PBS 1300a) [49]
3 U = 2?6 kV, f = 1 MHz, d = 2?18 mm 60 3000 PBS (Ca2+/Mg2+)+
1 g?L–1 D-glucose		 19?20d) [44]
COST microplasma jet 1.4 He 250 RPMI1640 75c) [50]
He+ O2 250 5c)
He+ H2O 250 25c)
He+ H2O+ O2 250 20c)
Tab.1  Concentration of hydrogen peroxide after treatment by APPJ from different authors and configurations (working conditions and measurement technique are specified for each device)
Gas Flow rate/
(L?min−1)		 Conditions t/s V/mL Liquid [NO2−]/(µmol?L−1) Ref.
He 0.05 U = 8 kV, f = 20 kHz,
d = 10 mm		 240 500 PBS (Ca2+/Mg2+) 1600a) [28]
0.05 U = 8 kV, f = 20 kHz,
d = 10 mm		 60 500 PBS (Ca2+/Mg2+) 400a) [28]
0.1 U = 8 kV, f = 15 kHz,
P = 5 W		 120 100 DMEM+FBS 340b) [29]
DI water 137b)
1 U = 7 kV, f = 10 kHz 300 4000 DI water 18c) [30]
1.67 U = 7.5 kV, f = 10 kHz,
d = 2 mm, shielding gas O2/N2		 600 2000 PBS 620c) [31]
2 U = 1.8 kV, f = 35 kHz 180 Serum-free HBSS 125?138b) [53]
2 U = 15 kV, f = 1 kHz,
d = 5 mm		 300 360 PBS 5a) [37]
2 U = 15 kV, f = 1 kHz,
d = 5 mm		 600 360 PBS 10a) [37]
2 U = 15 kV, f = 1 kHz,
d = 5 mm		 900 360 PBS 19.5a) [37]
3 U = 10 kV, f = 9.69 kHz 150 100 DI water 25a) [33]
DMEM 200a)
DMEM+ 10% FCS 500a)
5 U = 2 kV, P = 6 W,
d = 20 mm		 1800 4000 McCoy 435d) [36]
advDMEM 174d)
He+N2 2 U = 7.5 kV, f =10 kHz,
d= 15 mm		 600 2000 PBS 590c) [54]
Ar 1 U= 9 kV, f= 16 kHz,
d = 9 mm		 60 100 PBS 8.8a) [39]
2 U = 7 kV, f = 60 Hz,
d = 20 mm		 300 3000 DMEM+P/S+FBS 3350a) [40]
DMEM 2750a)
3 U = 0.7 kV, I = 3 mA,
f = 16 kHz, P = 0.2 W		 1800 DI water 10b) [42]
3 U = 7 kV, f = 10 kHz,
d = 15, 25 and 80 mm		 300 4000 DI water d = 15 mm, 11c) [43]
d = 25 mm, 16c)
d = 80 mm, 3.7c)
1, O2 U = 9 kV, f = 16 kHz,
d = 9 mm		 60 100 PBS <2.5a) [39]
1, N2 PBS <2.5a)
1, CO2 PBS <2.5a)
1, air PBS 1782a)
Ar, RF plasma jet 1.5 F = 13.7 MHz, d = 5?13 mm 60 3000 PBS (Ca2+/Mg2+)
+1 g?L−1 D-glucose		 250b) [44]
Ar, kINPen 3 U = 2?6 kV, f = 1 MHz 180 NaCl 10a) [48]
3 DPBS 6.5a)
3 Phenol free RPMI 1640 19.5a)
3 d = 10 mm 300 2000 PBS 500b) [49]
Tab.2  Concentration of nitrite ions in different liquids following APPJ or kINPen treatment
Gas Flow rate/ (L?min−1) Conditions t/s V/mL Liquid [NO3−]/(µmol?L−1) Ref.
He 0.05 U = 8 kV, f = 20 kHz, d = 10 mm 240 500 PBS (Ca2+/Mg2+) 500a) [28]
1 U = 7 kV, f = 10 kHz, d = 12 mm 900 100 DI water 2.4b) [55]
1 U = 7 kV, f = 10 kHz 300 4000 DI water 0.47c) [30]
1.67 U = 7.5 kV, f = 10 kHz, d = 2 mm, shielding gas O2/N2 600 2000 PBS 260c) [31]
3 U = 10 kV, f = 9.69 kHz 150 100 DI water 250a) [33]
DMEM 400a)
He+ N2 2 U = 7.5 kV, f = 10 kHz 600 2000 PBS 460b) [54]
Ar 3 U = 0.7 kV, I = 3 mA, f = 16 kHz, P = 0.2 W 1800 DI water 20c) [42]
3 U = 7 kV, f = 10 kHz 300 4000 DI water d = 15 mm, 0.9b) [43]
d = 25 mm, 1.5b)
d = 80 mm, 0.2b)
Air 1 U = 9 kV, f = 16 kHz, d = 9 mm 60 100 PBS 2580a) [39]
Ar, kINPen 3 U = 2?6 kV, f = 1 MHz, shielding gas O2 + N2 at 5 L?min–1 180 NaCl 7a) [48]
3 U = 2?6 kV, f = 1 MHz, shielding gas O2 + N2 at 5 L?min–1 180 DPBS 5a) [48]
Tab.3  Concentration of nitrate ions in solutions after APPJ treatment.
Gas Flow rate/(L?min−1) Conditions t/s V/mL Liquid [ROS]/(µmol?L−1) Ref.
He 1 U = 9 kV, f = 16 kHz, d = 9 mm 60 100 DI water OH•, 68 [57]
2 U =18 kV, f =24.9 kHz, d =10 mm 60 100 Aqueous solutions OH•, 23.5 [32]
HOO•, 17
O3/O2/O, 170
3 U = 10 kV, f = 9.69 kHz 150 100 DI water OH•, 4.12 [33]
DMEM OH•, 3
DMEM+ 10% FCS OH•, 0.4
N2 1 U = 9 kV, f = 16 kHz, d = 9 mm 60 100 DI water OH•, 130 [57]
Ar 1 OH•, 84
Ar+H2O 1 OH•, 210
O2 1 OH•, 32
CO2 1 OH•, 28
Air 1 OH•,<10
Ar, kINPen 3 Shielding gas O2, O2 + N2, flow rate 5 L?min–1 180 NaCl OH• + O2–, 1.9 [48]
DPBS OH• + O2–, 5.6
RPMI 1640 OH• + O2–, 3.6
Tab.4  Concentration of short-lived ROS detected by spin-trap after APPJ treatment, using different gases for plasma generation
Fig.3  Concentration ranges of RONS in PAM described in literature with emphasis on the nature of the liquid media
PAM tplasma/s [H2O2]max
/(mmol?L−1)		 [NO2−]max
/(mmol?L−1)		 Cell viability (Cv)
/%		 Cell lines Ref.
PBS(Ca2+/Mg2+) (1 h exposure followed by DMEM addition) 120 1300 1600 Cv24h≈ 4% Normal human skin fibroblasts (NHSF) [28]
480 Cv24h≈ 1%
120 Cv24h≈ 10% MRC5Vi cell line (derived from normal human lung fibroblasts MRC5)
480 Cv24h≈ 1%
120 Cv24h ≈ 45% Human colon cancer cells (HCT116)
480 Cv24h≈ 1%
120 Cv24h≈ 30% Melanoma cell line (Lu1205)
480 Cv24h≈ 1%
DMEM+FBS 120 14 340 Cv24h≈ 60.8%
Cv48h ≈ 45%–49%		 Glioblastoma (U87MG) [29]
DMEM/modified DMEM 240 35–42 – Cv72h≈ 40% Human breast cancer (MDA-MB-231) cells [34]
240 Cv72h≈ 15% Human glioblastoma (U87MG) cells
240 Cv72h≈ 20% Pancreatic cancer (PA-TU-8988T) cells
MEM+10% FBS 120 30 – Cv12h≈ 50%
Cv48h≈ 50%		 ScaBER (from human bladder cancer) [35]
240 Cv12h≈ 10%
Cv48h≤5%
RPMI 1640 20?300 6 – Cv24h≤10% Human hepatocellular carcinoma Bel7402 [38]
20 Cv24h≈ 92% 5-FU-resistant Bel7402/5FU cells
40 Cv24h≈ 80%
60 Cv24h≈ 60%
120 Cv24h≈ 40%
300 Cv24h≈ 10%
DMEM w/wo 10% FBS 180 110 3350 Cv24h ≈ 10%–12% Human glioblastoma cell line (U251SP) [40]
180 64a) 1740a) Cv24h≈ 95%–98% Human mammary epithelial cell
Line (MCF10A)
PBS 300 & 540 1300 500 Cv24h≈ 2%–5% Glioblastoma human GBM cell lines (U87, U251 and LN229) [49]
Tab.5  Correlation between RONS concentration generated by atmospheric plasma treatment in cell culture media by indirect treatment and the corresponding cell viability
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