Review on the Biomedical and Environmental Applications of Nonthermal Plasma

Abstract

Recent advances in atmospheric plasmas have led to the formation of nonthermal plasma (NTP). In recent decades, a number of novel plasma diagnostic approaches have been implemented and reported in order to better understand the physics of NTP. The use of NTP is a novel approach to producing reactive oxygen and nitrogen species. Plasma technology has many applications, including electrical device microfabrication, biomedicine, dentistry, agriculture, ozone generation, chemical synthesis, surface treatment, coating, and disease therapy. Furthermore, NTP is thought to be a successful strategy for the degradation of hazardous pollutants in the environment, making it a future hope. Recent studies showed that various operating parameters affect the yield of NTP-based technology. Especially, the presence of a catalyst, properly placed in an NTP reactor, leads to a significant increase in process performance as compared to NTP alone. Scientists have looked at using NTP in conjunction with catalysts to remove various sorts of pollutants from the environment. In this context, review articles are crucial due to the prevalence of NTP-based applications and ongoing developments. This review will describe recent advancements in NTP-based biomedical applications, bacterial inactivation, food preservation and storage, and environmental catalytic formulations. This review could be useful in providing a platform for advancements in biological applications and environmental protection through the use of NTP technology.

1. Introduction

The American physicist Irving Langmuir identified plasma as a fourth state of matter in 1922 [1]. Plasmas are gases that have been totally or partially ionized. In order to remove electrons from atoms, enough energy is given to the gas, resulting in a combination of free electrons, free radicals, neutrals, and positively charged species [2,3,4]. Nonthermal plasma (NTP) or cold atmospheric plasma differs from thermal plasma because of the properties of electrons, ions, and neutrality. The charge species, reactive oxygen species (ROS), reactive nitrogen species (RNS), electromagnetic field, electric field, ability to influence pH, visible light, charged particles, neutral species, ozone, and ultraviolet (UV) radiations were all found in NTP as shown in Figure 1, making it a feasible tool for a variety of tasks [5,6,7,8,9]. The temperature of plasma electrons might reach tens of thousands of kelvin, significantly exceeding the neutral gas’ temperature of roughly room temperature. In bulk, most plasmas are electrically neutral, which adds to plasma’s unique properties and categorization as the fourth state of matter. Plasma parameters can vary dramatically depending on the energy source and amount delivered. Furthermore, NTP devices such as jet plasma, dielectric barrier discharge (DBD) plasma, and spark plasma depicted in Figure 2a often operate in a room environment, making them ideal for life science research [9,10,11,12] and a wide range of biomedical applications [13,14,15,16,17,18,19,20,21,22]. Sterilization, skin disinfection, oral/dental disease treatment, blood coagulation, wound healing, cancer therapy, and immunotherapy have all seen new possibilities in medicine by using NTP [23]. Gliding arc discharge (Figure 2d) and corona discharge (Figure 2e) devices are commonly used for environmental applications such as the removal of gaseous pollutants.

1.1. Plasma

As plasma makes up 99% of the universe, it is the most prevalent kind of matter. The Sun and other stars, galaxies, solar winds, lightning, and the aurora borealis are all examples of the plasma state. Plasma televisions, neon and fluorescent lights, and plasma displays are well-known applications for man-made plasma. From Figure 1 and Figure 2c, it can be seen that plasma is made up of neutral, ionized, and/or excited charged particles, ions, and molecules, and ozone with the ability to influence the pH of solutions, as well as the existence of different ROS and RNS. A significant source of UV and vacuum UV radiation is plasma made up of several gases [24]. Plasma is a unique material treatment technology since it can employ a single component or a mix of components.

1.2. Thermal and Nonthermal Plasmas

All of the particles in a thermal plasma are at about the same temperature and completely ionized. Hot, completely ionized, and equilibrium plasma are other names for thermal plasma. Depending on the demands, equilibrium plasma is used in a variety of applications [25]. Plasma is a (partially) ionized gas made up of neutral species (molecules, radicals, excited species), ions, photons, and electrons. As the electron temperature is much higher than the temperature of heavy species (ions and neutrals) in nonthermal plasma (NTP) or non-equilibrium plasma, radicals and excited species are formed at temperatures that are closer to room temperature. This nonthermal energy distribution provides a potential route to getting around both the kinetic and thermodynamic constraints on the chemical conversion of reactants into desired products. Cold, partially ionized, atmospheric pressure, low temperature, and non-equilibrium plasma are other names for NTP. The NTP technology is suitable for treating a range of biological materials, including solids, liquids, and aerosols because it is at a low temperature when applied. There are several uses for two different types of NTP, low pressure and atmospheric pressure [26,27,28,29]. Although atmospheric-pressure plasma is only permitted in areas with strong electric fields, low-pressure plasma can spread across a considerable area [30]. When compared to low-pressure plasma, atmospheric pressure may offer more appealing applications. Plasma sustainability is frequently achieved via electric discharges. Despite the fact that the presence of reactive species affects the temperature of gas, it has a much higher chemical reactivity than the source gas. Atmospheric pressure plasma has been used in biological systems for practical reasons [28].

2. Generation of Reactive Species in NTP Discharge

The NTP is well recognized for generating exceptionally high concentrations of reactive species. NTP produces a variety of reactive oxygen species (ROS), including OH radicals, O₂, H₂O₂, O, O₃, and ¹O₂, as well as reactive nitrogen species (RNS), such as NO, NO₂, N₂O, N₂O₅, and atomic N [5]. Some of them, such as OH radicals, O, NO, N, and ¹O₂, have a short lifespan [19]. Helium plasma discharge was also applied by a number of studies [31,32,33,34]. The mechanisms by which ROS are produced in helium plasma jets have been well reported [35]. A number of species, including N₂⁺, atomic (He, O) radicals, and molecular OH, were discovered in helium discharge [32,34]. The RONS, also referred to as primary reactive species, are generated by the energy released during collisions between accelerating electrons and neutrals. In the gas phase right after the collision, electrons (e⁻), ionized neutrals and gas (M⁺), excited neutrals and gas (M*), N, O, atomic H, NO, and O₂*^- are produced [13]. They are categorized as primary reactive species [36], and the intensities of these species are very high in the plasma region. The lifetimes of primary reactive species are relatively short; for example, the lifespan of OH radicals, NO, and O₂*⁻, is 2.7 μs, 1.2 μs, 1.4 μs, and 1.3 μs, respectively [37]. Some of these reactive species immediately experience radiative decay, while others combine with neutrals, water molecules, and other reactive species. The main reactive species change into secondary reactive species such as H₂O₂, NO₂, NO₃, and O₃ [38] in an ambient environment_, as shown in Figure 3. The liquid phase (or another target) is where the RONS produced in the gas phase dissolve and form tertiary reactive species. The tertiary reactive species are formed when the RONS produced in the gas phase dissolve in the liquid phase [36]. Long-living reactive species include O₃, H₂O₄, NO₃, and NO₂ because of their lifespans of a few milliseconds over several days [39]. Water can dissolve H₂O₂, NO₂, and NO₃; NO₂ and NO₃ are immediately converted into NO₂⁻ and NO₃⁻, respectively [13,40]. Depending on the plasma source, working gas, power source, treatment time, and sample volume, these reactive species can reduce the pH of the target liquid by up to 2 [40]. However, whether a target is dry or aqueous affects the chemistry of ROS and RNS formation in a target [40]. The target, gas region, plasma/target interface, and discharge region of RONS formation are schematically depicted in Figure 3.

DBD plasma and jet plasma have been shown to produce high levels of ROS [26,41,42]. Indirect plasmas are produced between two electrodes of certain devices and transferred to the application region through a gas flow. ROS are often produced at the border of jets with the surrounding air by a variety of causes. Several authors claim that ROS generated by plasma can induce morphological alterations, membrane depolarization, lipid peroxidation, and DNA damage in cells [43,44,45,46]. The transport of reactive oxygen/nitrogen species (RONS) is the major mechanism of NTP anti-neoplastic action [47]. The quantity of reactive species created in plasma-treated liquids is extremely important in plasma therapy. Several lines of study now focus on utilizing plasma to treat cancer using the ROS generation feature [48,49,50]. In human cells, plasma treatment induces the mitochondrial membrane potential to depolarize, resulting in the generation of ROS [51]. The therapeutic effects of air plasma have been linked to the generation of RONS such as H₂O₂, Ox, OH, •O₂, and NO_x as a result of mitochondrial membrane potential depolarization and ROS accumulation [49]. Previous reports provide a more thorough explanation of plasma–liquid interactions and the plasma roadmap [23,52,53].

3. NTP Application for Cancer Treatment

The NTP technology has advanced dramatically in the previous two decades, from theoretical and experimental study to real-world implementations. The generation of plasma at atmospheric pressure and room temperatures to deal with biological systems has given rise to a new multidisciplinary field known as “plasma medicine” [2]. NTP has a variety of potentials in biomedical engineering nowadays [54]. Figure 4 depicts the interaction of NTP with the biological system, indicating the main molecular mechanisms involved in the use of LTP in cancer treatment. NTP technology has the potential to provide a less intrusive surgical procedure for removing particular cells without causing injury to the surrounding tissue. Traditional laser surgery relies on heat contact, which can result in unintentional cell death (necrosis) and lasting tissue damage. NTP contact with tissue, on the other hand, may allow selective cell elimination without necrosis [55]. Cell detachment without influencing cell viability, regulated cell death, and other interactions are examples of these interactions. It can also be employed for cosmetic approaches to dermis reticular architecture regeneration.

The goal of plasma contact with tissue is to operate below the temperature damage threshold and cause chemically specific reactions or alterations, rather than to denature the tissue. The presence of plasma, in particular, can enhance chemical processes that have the desired effect. Pressure, gas composition, and power may all be adjusted to enhance chemical reactions. As a result, finding plasma conditions that generate a positive influence on tissue without having heat treatment is crucial. NTP produces a variety of reactive species that can be employed to increase cancer cells’ oxidative stress and ultimately kill them [41,57,58]. Different ROS can be produced in plasma, and some of them can cause oxidative stress in cells [47]. As a result, it can alter any pathway that is regulated by or connected to ROS, either directly or indirectly [41,59]. Recent research has found that cancer cells generate more ROS [60] and are thus prone to oxidative stress higher than normal cells, making them more appropriate for targeting by ROS in combination with plasma technology [61,62]. Because NTP-killing activity is greater in cancer cells than in normal cells, the outcome of an NTP cancer treatment is more optimistic [62]. NTP medicinal applications have achieved this incredible breakthrough from initial discovery through fundamental scientific research to clinical applications [63].

Previous studies dealt with the optimal duration of treatment to maximize plasma’s anticancer effects [33,64,65,66]. The improvement of plasma on-time during treatment is a critical issue that needs to be addressed. The biomedical effects are directly impacted by RONS levels, which are directly impacted by plasma on-time. Recently, research on the effects of plasma on-times was conducted while keeping the duty ratio and treatment time fixed (Figure 5) [67]. The selected plasma on-times are 25, 50, 75, and 100 ms for 10% and 36% duty ratios, respectively. Figure 5a–c depict, respectively, the experimental setups, a photo taken during the preparation of PTM using a soft plasma jet, and the application of PTM to cells. Figure 5d,e show that the NO_x concentration in PTM corresponds to the plasma on-time, in 10% and 36% duty ratios. Similarly, Figure 5f,g show the concentrations of H₂O₂. Figure 5h,i indicate the viability of the U87-MG cell line when PTM was applied. It is interesting to note that by increasing the plasma on-time, the levels of ROS/RNS dramatically increased in PTM and significantly impacted the viability and ATP levels of the U87-MG cell line. The findings of this study offer a significant indication of progress by introducing the optimization of plasma on-time to enhance the effectiveness of the soft plasma jet for biomedical applications [67]. It is interesting to observe from this research that the ROS/RNS levels can be altered to suit needs by adjusting the plasma on-time within the fixed duty ratio and treatment time.

A new cancer treatment modality is being developed by the multidisciplinary field of plasma medicine, which combines plasma physics, chemistry, biology, and clinical medicine. In order to specifically target malignant cells for the prevention of cell proliferation and tumor progression, it primarily relies on the use of low-temperature plasmas in atmospheric pressure. A comprehensive discussion is given of intracellular mechanisms of action, important pathways, and the selectivity of NTP against cancer cells as shown in Figure 4. The in vivo, in vitro, and in ovo experiments are all studied using the NTP technology. Figure 6 depicts two recent in vivo and in ovo experiments using NTP for anticancer purposes. According to reports and widespread knowledge, the NTP raises the rate of apoptosis in cancer cells when compared to the control group (Figure 6a) [68].

There is still a lack of understanding of the molecular mechanisms underlying NTP’s therapeutic effect on thyroid cancer. Understanding the anticancer effects of NTP-activated medium (NTPAM) on thyroid cancer cells and clarifying the signaling mechanisms causing NTPAM-induced thyroid cancer cell death was explored in a recent study [68]. The in vivo analysis demonstrates that, when compared to control groups, NTPAM-treated groups had significantly lower tumor weights (Figure 6b). The findings of the reported study showed that NTPAM inhibited THCA cell growth more potently than the control did and that ROS controlled EGR1/GADD45α to mediate NTPAM-induced apoptotic cell death (Figure 6c). Recent research offers a fresh understanding of the basic chemical mechanisms underlying NTP–cancer cell interactions as well as a previously unrecognized benefit of current NTP cancer therapy: lowering immunosuppressive signals on the surface of cancer cells (Figure 6g–k) [69]. Researchers can better explain many disagreements by having a thorough understanding of the underlying mechanisms. This includes choosing the best plasma parameters to regulate the combination and concentration of reactive species, delivering plasma to deep-lying tumors, and figuring out the best plasma dose to achieve particular clinical translational outcomes. Designing low-temperature plasma sources that satisfy medical device technical standards is a unique approach for cancer therapy in clinical trials, but it still has to be safer and more effective.

Table 1. An overview of recent NTP developments for anti-cancer applications.

Plasma Type	Treatment Time	Method	Cell Type	Main Findings	Ref.
Plasma jet	60 and 120 s	in vivo	MCF7 and HCC1806	After CAP treatment, apoptosis appears to be the most common type of cell death, though the HCC1806 cell line also demonstrated a sizeable percentage of cells going through necrosis. Cell cycle arrest happened in the G2/M phase. Only in HCC1806, where higher nitric oxide levels were observed, is it possible that nitrite reductase activity is naturally higher.	[70]
Microwave plasma	60, 120, 180 s (PAM)	in vitro and in vivo	A549 and H1299	PAM induces ferroptosis in human lung cancer cells, which promotes cell death. Lipid peroxidation, and a decrease in FSP1 expression after PAM treatment. PAM causes mitochondrial dysfunction by raising intracellular and lipid ROS. PAM inhibits tumor growth in a xenograft model.	[71]
DBD(CAP)	2–6 min	in vitro	MDA-MB231, Hs578T and MCF-7	Both ER+ and ER- cells underwent drastic phenotypic changes after receiving CAP treatment. Elevated Bax/Bcl-2 ratio and the cleavage of PARP-1, after CAP treatment. When compared to other proteins, proteases, and inflammatory mediators, CD44 protein expression was significantly decreased by CAP. Breast cancer cell growth is inhibited by CAP, which also controls a number of tumor microenvironment effectors.	[72]
Pulsed streamer discharge	-	in vivo	CT26 tumor-bearing mice	Occasionally, radiotherapy and plasma therapy show an antitumor abscopal effect. Plasma irradiation of healthy tissue delayed the growth of the tumor.	[73]
Cold atmospheric plasma jet	-	in vitro	A431 skin carcinoma and MX7	When using the grounded substrate for both cell lines, there is a stronger suppression of the viability of the cells. The use of a grounded electrode beneath the bio target has the potential to effectively harm tumor cells with less radiation exposure.	[74]
Argon plasma jet kINPen	3 or 6 min	in vitro and in vivo	U251 and U87	Glioblastoma was inhibited by H2O2 in combination with vitamin C and plasma-conditioned medium. Combination of vitamin C and plasma-conditioned medium treatment increased aquaporin-3. The JNK signaling pathway is activated by the combined effects.	[75]
Plasma jet kINPen	5, 10, and 20 s	in vitro	786-O, caki-1 and HREpC, Renel cell carcinoma (RCC)	The proliferation of RCC cells is significantly reduced by plasma treatment. The induction of apoptosis as well as the impairment of cytoplasmic membrane and cell cycle functions. It would be highly beneficial clinically to combine NIPP treatment with low-dose chemotherapy in the future.	[76]
Kinpen 09, plasma jet	5 and 15 s	in vitro	LN-18,U-87	Compared to controls, growth was seen to decline over time as the treatment progressed. AKT serine/threonine kinase 1 (AKT1) and extracellular-regulated kinase 1/2 (ERK1/2) expression were both decreased as a result of plasma treatment. Tumor-suppressive microRNA-1 (miR-1) expression was found to be strongly upregulated in both cell lines following exposure to plasma.	[77]
Cold atmospheric plasma jet	45 and 90 s	in vitro andin vivo	B16 and L929	In vitro and in vivo studies were conducted to determine how starvation and plasma treatment combined to affect melanoma. In vitro, starvation + plasma altered the cell morphology of murine B16 cells but not L929 fibroblasts. Metabolic activity decreased and lipid peroxidation increased along with apoptosis and DNA fragmentation. Starvation decreased the tumor burden in vivo. Compared to plasma exposure alone, the level of Lc3 and Atg5 in the tumor tissue increased more.	[78]
Cold atmospheric plasma jet	2 min	in vitro	A549, Wi-38, and MRC5	Plasma + Chloroquine (CQ), an autophagy inhibitor, synergistically increased the death of A549 cancer cells and had little effect on the viability of Wi-38 cells. Downregulation of Drp1 and overexpression of PINK1 proteins in plasma + CQ-treated cells suggested that CQ aggravated plasma-dependent mitochondrial instability. Due to the disruption of autophagosome formation and mitochondrial homeostasis, CQ increased plasma-dependent cell death.	[79]
No-ozone cold plasma (NCP)	5 min	in vitro andin vivo	SCC25,YD-10B, MG63,Hs68 and HaCaT	After 1 week of p-FAK/GNP + NCP treatment, the tumor’s size was reduced by half, and by the end, the majority of tumor tissue had vanished. Combining gold nanoparticles with the p-FAK antibody, or p-FAK/GNP, can instantly and selectively harm SCC-25 cells in both in vitro and in vivo. p-FAK/GNP + NCP treatment resulted in instantaneous cell death only in SCC25 cells but not in HaCaT cells.	[80]
Cold atmospheric plasma	5, 10, and 20 s	in vitro	CAL-78, SW1353	The level of glucose in the cell culture medium rose following CAP therapy. The migration assay revealed that the CAP treatment reduced the motility of chondrosarcoma cells.	[81]
DBD, plasma-activated medium (PAM)	15,30 and 60 s	in vitro	MCF-7, MDA-MB 231	PAM was able to raise Paclitaxel’s (PTX) cytotoxicity as the breast cancer cells’ ability to survive declined, and this effect persisted over the course of lengthy trials. PAM may enhance the anti-cancerous effects of PTX.	[82]
DBD, plasma-activated saline (PAS)	10 min	in vivo	A375, Tca-8113, and A549	In vivo, PAS also reduced cell proliferation in non-small-cell lung cancer and oral tongue squamous-cell cancer. When compared to saline, PAS therapy in melanoma significantly reduced tumor growth, and tumor growth in vivo was unaffected by a low pH environment.	[83]
kINPen	15–120 s	in vitro	PC-3, Human bone marrow mesenchymal stem cells (hBM- MSCs)	An injectable anticancer treatment based on oxidative stress is plasma-conditioned liquids. They enhance doxorubicin cytotoxicity, down-regulate drug resistance genes, and suppress redox defenses. Combination improved prostate metastatic bone cancer targeting versus benign cells.	[84]
Nanosecond pulsed dielectric barrier discharge (nspDBD)	10 s	Ex vivo	J-Lat CD4+ T lymphocytes, primary CD8+ T lymphocytes	The addition of NTP to the J-Lat T-lymphocyte cell line (clones 10.6 and 15.4) improved monocyte recruitment and macrophage maturation, two crucial steps in the initiation of an immune response. Ex vivo application of NTP to latently infected lymphocytes can cause significant immune cell responses, advancing the development of an NTP-based immunotherapy that will enable ART-free management of HIV-1 reactivation in HIV-positive people (PLWH).	[85]
-	1–10 min	in vitro	HeLa	Plasma-activated ringer lactate solution (PAL), in addition to containing H2O2, also contains one or more active compounds or species that are capable of killing HeLa cells. The identification of the active component(s) in PAL may lead to the development of manufacturing anticancer drugs for use in the future in the treatment of cancer.	[86]
Nonthermal atmospheric pressure plasma (NTAPP)	30, 60, 90, and 120 s	in vitro	Adipose tissue	Cell cycle studies revealed that NTAPP can, at relatively low dosages, promote proliferation and quicken the cell cycle. To boost the efficiency of ADSCs in vitro cultivation, NTAPP may be used in the fields of stem cell therapy and regenerative medicine.	[87]
DBD	-	in vitro	NTP-resistant cell line (A375-NTP-R), A375	Cells exposed to NTP continuously developed a tenfold increase in resistance compared to the parental cell line of the same passage in terms of their half-maximal inhibitory concentration (IC50). Despite exhibiting less apoptosis, NTP-resistant cells were more prone to lipid peroxidation and ferroptosis. NTP-resistant cells favored aerobic glycolysis, according to sequencing and metabolic research.	[88]
Nanosecond pulsed dielectric barrier discharge (nsDBD)	10 s	in vitro	Jurkat T lymphocytes and THP-1 monocytes	Increased immunogenicity of blood cancer cells brought on by NTP may not always lead to cytotoxicity. Results serve as an early-stage foundation for work that aims to develop an ex vivo NTP-based immunotherapy for hematological malignancies.	[89]
Nanosecond pulsed dielectric barrier discharge (nspDBD)	10 s	Ex vivo	J-Lat CD4+ T lymphocytes, primary CD8+ T lymphocytes	After NTP treatment, CD47 is immediately regulated, and simulations reveal potential oxidized salt bridges responsible for conformational changes. IHC analysis showed that all three human cell lines—glioblastoma, melanoma, and head and neck squamous cell carcinoma—expressed less CD47 than controls soon after NTP therapy.	[69]
Soft plasma jet	1, 3, 5, 7 min	In vitro	U87-MG	By keeping the duty ratio and the treatment time fixed, the effect of plasma on-times is investigated. By elevating plasma on-time 25, 50, 75, and 100 ms, electric conductivity (EC) and oxidation reduction potential (ORP) of DMEM increased, but pH remained unchanged. Increasing the plasma on-time, the levels of ROS/RNS in PTM rose dramatically, which had a significant impact on the viability and ATP of U87-MG cells. ROS/RNS levels can be adjusted as required by altering the plasma on-time.	[67]

provides a summary of some recent NTP developments made by researchers for anti-cancer applications.

4. Role of Plasma Technology in Food Decontamination and Storage

4.1. Microbial Inactivation

Plasma technology’s source of ROS and RNS is mainly concerned with increasing the yields of cultivars by stimulating seedling growth and inactivating microorganisms to increase the shelf life of food storage and fulfill the scarcity of food from all over the world [90,91]. Several treatment methods increased the concentration of intrabacterial reactive species such as H₂O₂, NO₃, NO₂, and O₃. These reactive species are caused by oxidative stress, which prevented the ability of biofilms to regenerate [92]. The inactivation of E. coli bacteria was reported due to the UV radiation produced during the PAW [93]. The PAW has bactericidal properties due to the RONS. Conidium is an asexually generated fungal spore, a notorious plant disease inhibited by the reactive species in the PAW [94]. Most crops are destroyed by serious diseases by wall-less bacteria called phytoplasmas. Yellow grapevines can easily become infected with phytoplasma [95]. Phytoplasma caused disease in yellow grapevines controlled by the plasma-treated liquids which stimulate the defensive enzymes stilbene synthase and phenylalanine ammonia. The presence of RONS in PAW solution results in oxidative stress, which activates the stilbene metabolic pathway and increases the antioxidant properties. Resultantly, the research shows that PAW treatment can be used to enhance plants’ resistance to diseases [96].

4.2. Effect of NTP on Biofilms

Biofilms are multicellular communities of microbial cells, connected to a surface indefinitely and enveloped by a matrix predominantly consisting of polysaccharides, extracellular nucleic acid, and protein. In nature, more than 95% of the bacteria exist as a biofilm which favors their growth on solid surfaces [97]. Bacterial biofilm formation involves many steps. Quorum sensing is a special type of signaling required which occurs between microbial cells, and the transcription of a different set of genes is also a basic requirement for biofilm formation. Bacterial inactivation or bio-decontamination, as well as the sterilization of surfaces by NTP, have gained a lot of interest in recent years [98]. It is well-known that NTP has antibacterial effectivity and can inactivate planktonic bacteria, yeast, and spores. The effects of plasma application on biofilms seem to be a promising new direction in biofilm removal technology [99]. Since NTP, particularly atmospheric-pressure plasma jets (APPJs), are frequently operated at temperatures close to room temperature, they can be used directly on heat-sensitive materials such as human tissues. Due to the APPJs’ transitory character and accompanying thermal non-equilibrium, the plasma chemistry is improved, and charged species are transported to the targets quickly and efficiently [100]. The reactive species formed by plasmas are expected to comprise a combination of charged particles and chemically active species producing ultraviolet (UV) light (e.g., O₃, O₂, NO, H₂O₂, and OH) which contribute to the anti-microbial effects by inflicting damage on DNA, lipids, proteins, etc., leading to cellular structure degradation [101]. As we know, bacterial biofilms consist of DNA, proteins, and polysaccharides which are affected or damaged by plasma-generated reactive species which are made up of charged particles and chemically active species and the generation of UV radiation.

4.3. Sustaining Food Freshness and Storage

NTP technology has been suggested as an advanced method to increase food freshness and food storage for longer use. The freshness of freshly cut lettuce was reported to be maintained for a long time after washing with PAW. The lettuce tissue organelles were sustained as fresh properties such as color, texture, and taste after washing with PAW treatment [102,103]. PAW treatment has the ability to maintain the freshness of fresh-cut kiwifruit. Kiwifruits were sprayed with PAW solution or deionized water and submerged in S. aureus suspension. The reactive species in PAW generated oxidative stress, which in turn damaged the membrane of bacterial cells and ultimately lead to cell death. Furthermore, PAW treatment had no detrimental effects on the kiwifruits’ quality. They were less affected by reactive species oxidative species damage due to the antioxidant enzymes in PAW [104]. Plasma therapy effectively suppressed B. cinerea spore germination and mycelial development in vitro, as well as gray mold decomposition in blueberries infected with B. cinerea during postharvest storage [105]. Figure 7 shows the action of NTP on bacterial cell structures, resulting in functional loss and sterilization which helps in food preservation.

The microbial inactivation in a liquid substrate is mostly caused by oxidative stressors brought on by the reactive species, and NTP is regarded as an improved oxidation approach. Typically, seed treatment is conducted to guard against infections that could harm seeds during the early stages of seedling development. If this phase is skipped, pathogens, insects, and plant diseases will only attack, disrupting the germination process and plant growth. However, some seed treatments that use chemicals can be extremely detrimental since they expose people to chemicals when treating large amounts of seeds, which can lead to inadvertent poisoning, damage to the seeds, and risk for farmers or workers. The presence of microorganisms (bacteria and fungus) that will impact crops is the industry’s top concern right now. Recently, the agriculture sector has implemented a number of methods to limit the growth of bacteria and fungi on crops. The creation of bacterially resistant strains, the use of chemical fumigants, the drainage of the soil, and particular plowing techniques are a few of the methods used to manage bacteria in the agriculture sector. The denaturation of proteins, lipids, and other micronutrients during some of these reactions, however, could result in unfavorable alterations to the nutritional quality of food. Furthermore, when applying this technology for food applications, it is important to thoroughly research the genotoxicity of reactive species. The application of cold plasma for microbial eradication can be used across a variety of food substrates, including cheese, fruits, and meat products. In addition, it is utilized to modify the rate at which seeds germinate. It is an environmentally friendly method that is utilized as an alternative to conventional methods for food preservation and other possible uses. The Summary of recent NTP advancements for applications in food preservation and bacterial inactivation are provided in

Table 2. Summary of recent NTP advancements for applications in food preservation and bacterial inactivation.

Plasma Type	Treatment Time	Microorganism	Main Findings	Ref.
Surface dielectric barrier discharge (SDBD)	20 min	Escherichia Coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes	Tomatoes are efficiently sanitized using plasma bubble-activated water (PBAW). Color of tomatoes remained unaffected after PBAW treatment. The H2O2, NO2, and NO3 concentrations increased by increasing plasma treatment time. Reactive species played key role in membrane lipid oxidation of bacteria for inactivation.	[107]
Nonthermal atmospheric pressure plasma	3 h (for PAW preparation)	Danio rerio (zebrafish), Escherichia coli and Enterococcus faecium	Varying RONS PAW solutions evaluated the acute toxicity (OECD 236) of zebrafish embryo. The H2O2 concentration threshold for zebrafish was determined to be 30 mg/L. The pH of the solution affected the NO3 threshold, which varied from 7 to 15 mg/L. The pH threshold for zebrafish death was found to be 3.85. Pathogen growth was effectively slowed down or even completely stopped by non-toxic PAW.	[108]
Plasma jet	3 min and 5 min at 15 kV, 30 kV	Bacillus subtilis DSM 618	Briefly, 2-log reduction in B subtilis vegetative cells and 1-log reduction in spore-contaminated black pepper grains archived after plasma treatment. Spoilage germs successfully inactivated by using plasma treatment. Key quality indicators for dried ingredients did not significantly degrade.	[109]
Nonthermal atmospheric plasma (NTP) (Plasma jet)	(60–120 s) At 15 or 40 mm and gas flow rates (2000–3000 L/h), (25 kHz-100% V)	Salmonella enterica serovar Enteritidis (ATCC BAA-1045)	Serovar Enteritidis concentration on egg surface was reduced below the detection limit (102 cfu/egg) after 120 s of NTP treatment. On eggshells, Salmonella enterica serovar Enteritidis was significantly inhibited. The decontamination impact improved with rising plasma power and treatment duration. No observable difference in egg quality after plasma treatment.	[110]
Hybrid plasma discharge (HPD) reactor	10, 20, and 30 s (0.5–5 L water)	Escherichia coli O157:H7 (700728™)	With a single power source, the HDP reactor created plasma discharges in both electrodes. PAW was produced with a very high inactivation rate and high energy efficiency. The HPD reactor’s energy efficiency increases by reducing the orifice diameter. The energy efficiency rose to $0.181 \mathrm{mol}·{\mathrm{kW}}^{-1}·{\mathrm{h}}^{-1}$0.181 as salinity increased. Escherichia coli inactivation was reduced by 5.18-log10 in under 30 s treatment time.	[111]
Surface discharge plasma	5 min and 10 min(PAW)	SARS-CoV-2 RBD and human ACE2 proteins	PAW inactivates the pseudoviruses with SARS-CoV-2 S protein. Through modification, PAW inactivated the receptor-binding domain (RBD) binding activity. Inactivation was greatly aided by the short-lived reactive species (ONOO−) in the PAW. After 30 days at room temperature, PAW was still able to significantly reduce the RBD binding to hACE2.	[112]
Dielectric barrier discharged cold plasma (DBD-CP) combined with Lactobacillus panis C-M2	Lactocin C-M2 dosage of 0.90 mg/g combined with DBD-CP at voltage of 60 kV for 92 s,	Staphylococcus aureus, Shigella flexneri, Bacillus spp, Lactobaillus spp, Escherichia coli, Pseudomonas aeruginosa	Lactocin C-M2, used together with the DBD-CP, is effective in food preservation. After being exposed to DBD-CP, lactocin C-M2 exhibited stable antibacterial activity. Fresh white fish for 90 s at 60 kV combined with 0.9 mg/g Lactocin inhibits microbial growth. Food preservation is more effective with the synergistic effect of the Lactocin C-M2 and DBD-CP.	[113]
Dielectric barrier discharge (DBD)-atmospheric cold plasma (ACP)	5, 10, 15, and 20 min (PAW)	Methicillin-susceptible S. aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA)	Inactivating S. aureus on chicken breast with PAW, a disinfectant without chlorine. MRSA and MSSA can be removed more than 99% with PAW. Resistance of MRSA and MSSA to PAW is negligible. Surface color of the chicken breast was unaffected by PAW.	[114]
nonthermal atmospheric pressure plasma system (DE-21436, Marschacht, Germany)	30, 60, 90, and120 min (PAW)	Escherichia coli (E. coli)	E. coli on broccoli sprouts was successfully inactivated by PAW treatment. The largest decline in E. coli was observed in PAW60 after a 15 min treatment. On the physicochemical characteristics of broccoli sprouts, PAW had no adverse effects. Following PAW treatment, sulforaphane formation slightly increased.	[115]
Cold atmospheric plasma (CAP), DBD reactor helium-oxygen plasma	10 min	Salmonella Typhimurium, Listeria monocytogenes	Although, L. monocytogenes is more resistant to CAP treatment, similar trends of inactivation observed as in S. Typhimurium. The log reductions in the range [1.0–2.9] for S. Typhimurium and [0.2–2.2] for L. monocytogenes after CAP treatment. Food intrinsic factors must be taken into consideration when developing a plasma treatment plan because the food structure affects the cell inactivation behavior and effectiveness of CAP.	[116]
Atmospheric air plasma (AAP) or acoustic airborne ultrasound technology (AAU)	AAP for 3, 5, and 10 min and AAU for and 15, 30 min	Escherichia coli and Listeria innocua biofilms	Both of the atmospheric air technologies evaluated for biofilm cell inactivation effects for L. innocua and E. coli biofilms. For both early and mature-stage biofilms, atmospheric air plasma treatment outperformed airborne acoustic ultrasound treatment. AAP treatment for 5 min significantly decreased the number of E. coli and L. innocua biofilm cells by 3.5 to 4.5 Log CFU/coupon and the metabolic activity by 54%. Rise in intracellular RONS led to oxidative stress and accelerated bacterial cell death.	[117]
Plasma-treated water (PTW)	0h-PTW, 1h-PTW, and 7D-PTW	Escherichia coli	According to PTW treatments, the target bacteria and post-discharge time affected the degree of disinfection. The effectiveness of PTW for E. coli disinfection was maintained for 1 h but decreased when PTW aged for 1 week (7D-PTW). After treatment with freshly made 0h-PTW, there was only a marginal decrease in food-borne bacteria. Sliced potatoes treated with various types of PTW showed no or negligible changes in color, weight loss, hardness, and pH.	[118]
Jet-based DBD system	5, 10, and 15 min at 10, 15, 20 kV	Aspergillus flavus (PTCC NO.5004) and aflatoxin level by HPLC	In comparison to other factors, raising the voltage had the biggest impact on lowering Aspergillus flavus. In comparison to other factors, lengthening plasma exposure time had the biggest impact on aflatoxin reduction. The most effective reduction in fungi was achieved with a plasma exposure time of 15 min, a voltage of 20 kV, and an argon/air ratio of 62.23%. To lessen toxicity and fungal contamination, this technique can be used as a substitute for the thermal process.	[119]
CAP jet system	2.5, 5, 7.5, 10, and 15 min	Aspergillus flavus and Aspergillus niger	A. flavus and A. niger were substantially prevented from spreading on peanuts CAP. After receiving CAP treatment, fungus spores were damaged. In comparison to other treatment groups stored for 29 days, the treated group with 200 W for 5 min had significantly lower aflatoxin concentrations and A. flavus growth. The peanuts treated with CAP maintained oil quality indices in the good quality range.	[120]
DBD plasma	15, 20, and 25 min (PAW)	E. coli	The PAW treatment reduced the E. coli on the surface of button mushroom. The browning and softening of the button mushroom were delayed by PAW. It is a novel way to preserve fresh produce when PAW is used with a suitable activation time.	[121]
Cold plasma (PAW)	PAW was mixed with each organic matter solution (9: 1, v/v) and the mixture was placed at room temperature for 15 min. n,	E. coli O157:H7 and S. aureus	E. coli O157:H7 and S. aureus can be efficiently inactivated in suspension with PAW. Inactivation ability of PAW is reduced by beef extract and peptone. Organic substances have an impact on PAW’s physicochemical characteristics. Before using PAW, it is necessary to remove organic matter.	[122]
Atmospheric cold plasma (DBD)	10 and 20 min	Escherichia coli, Salmonella enterica, and natural microflora	ACP inactivates spoilage microbes (Escherichia coli, Salmonella enterica, and natural microflora) on wheat grains and enhances the quality and safety of flour. A 20 min treatment shows the log CFU/g reductions were 4.84 for E. coli, 4.40 for S. enterica, 0.96 for mesophiles, 2.14 for psychrotrophs, and 1.38 for Enterobacteriaceae.	[123]
Atmospheric cold plasma (ACP)	1 h	Listeria monocytogenes	ACP treatment maintained the quality of ham in package storage conditions and reduces the Listeria monocytogenes infectivity. Briefly, 24 h storage after treatment significantly reduced the growth of Listeria monocytogenes which is 4-log CFU/cm2 and after 7 days of storage, the reduction rate is below the detected limit. Significant changes were detected in lipid oxidation and color after post-treatment storage.	[124]
High-voltage cold atmospheric plasma (HV-CAP) combined with Squid Pen Chitooligosaccharide (COS)	5 min	Psychrophilic bacteria, Clostridium perfringens, lactic acid bacteria, enterobacteriaceae, pseudomonas, and hydrogen sulfide (H2S)-producing bacteria	HV-CAP with chitooligosaccharide enhanced the shelf-life of Asian sea bass slices to 12 days. Treated bass slices have the lowest total volatile base and trimethylamine during storage. COS addition prevented oxidation of polyunsaturated fatty acids in slices induced by HV-CAP and reduced the lipid oxidation and protein. COS prevented. The combined effect of HV-CAP with COS significantly sustained the shelf life of sliced Asian sea bass for 12 days.	[125]
Direct high-voltage atmospheric cold plasma (DBD	2–5 min	Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, and Tulane virus	For the salmonella inactivation on chicken breast 3.5 min plasma treatment at 39 KV is effective, the reduction rate is 3.7-log CFU/cube. For the E. coli 3.9-log CFU/cube, L. monocytogenes 3.5-log CFU/cube, and Tulane virus 2.2 PFU/cube, reduction was observed. Chicken breast efficiently sanitized using ADC plasma treatment of 5 min, and the treatment conditions did not affect the color of chicken breast.
High-voltage atmospheric cold plasma	2–5 min	spoilage bacterium Pseudomonas spp	Cold plasma has the ability to inactivate spoilage bacteria and maintain the shelf-life of food during storage. Plasma treatment of 5 min on spinach leaves and cold storage of 7 days reduces the microorganisms by about 3.51 log10 CFU. Quality and moisture of spinach leaves was maintained for 7 days storage after plasma treatment	[126]
Nonthermal plasma (NTP)	-	Porcine Reproductive and Respiratory Syndrome (PRRS) virus and bacteriophage MS2	Inactivation of PRRSv was achieved with NTP powered at 20 kV. A 1.3-log reduction was attained by the treatment of NTP. The non-enveloped MS2 and enveloped PRRSv were inactivated by NTP treatment.	[127]
Dielectric barrier discharge (DBD) plasma	5 min	mesophiles, Enterobacteriaceae, and psychrotrophs	Cold plasma has a negligible effect on color, pH, and water-holding capacity of poultry meat. For the 5 min treatment, 1.5 log CFU/g reduction in mesophiles, Enterobacteriaceae, and psychrotrophs was confirmed in-package storage for 24 h. Plasma treatment enabled an additional 6 days of microbiological shelf life when stored in the refrigerator.	[128]
Atmospheric dielectric barrier discharge cold plasma (CP)	1, 2, and 3 min	Salmonella strains: S. enteritidis (CCARM 8040), S. typhimurium DT104 and S. montevideo (CCARM 8052)	A combination of hydrogen peroxide (H2O2) and in-package CP therapy was successful in inactivating foodborne pathogens in cabbage slices that were packaged in PET containers. Salmonella concentration is decreased whereas lipid peroxidation, ROS, and the number of non-viable cells are increased. The antioxidant activities or color of cabbage slices are unaffected by H2O2-CP treatment.	[129]
High-voltage cold plasma (HVCP)	0, 5, 10, and 15 min	Pseudoalteromonas aliena, Lysinibacillus macroides, Pseudomonas lundensis, Shewanella baltica, Pseudoalteromonas haloplanktis, Paenisporosarcina quisquiliarum, and Brochothrix thermosphacta	HVCP treatment maintained the shelf-life of blue swimming crab lump meat and there is no impact on its color. The decrease in polyunsaturated fatty acid contents was observed in treated samples. Ten minutes of treatment showed a promising effect on shelf life longer than 12 days at 4 °C.	[130]
Cold atmospheric plasma torch (CAPT)	30, 60, 90, and 120 s	Escherichia coli and Bacillus cereus	Surface of Olivier salad decontaminated by the CAPT, treatment given to sample at a 3 cm distance for 90 s. Microbial maximum inactivation was achieved at 120 s treatment, which has been 3.77, 2.91, and 1.52 log CFU/g for coliform, total viable count (TVC), mold and yeast, respectively. The product is successfully ready to eat because the CAPT treatment had no appreciable effect on its sensory properties.	[131]
Cold plasma-generating paper-based electrodes (CPPE)	10 min	E. coli and Listeria innocua	For the reduction in E. coli on spinach leaf, the 10 min CPPE treatment was effective. Reduction in E. coli for spinach leaf was 4.6 ± 0.6 log CFU and for tomato, 4.6 ± 0.5 log CFU. For Listeria innocua on the spinach leaf, the reductions were 4.8 ± 1.7 log CFU per spinach leaf and 2.0 ± 0.4 log CFU per tomato. ROS produced by plasma are responsible for fresh produce decontamination. CPPE has no negative effect on quality of spinach and tomatoes. Depending on the type of bacteria, food surface, and electrode parameters, inactivation may occur.	[132]
Dielectric barrier discharge (DBD) plasma	30, 180, and 300 s	-	With increased cold plasma (CP) processing time, the inactivation rate increased. With longer treatment times, raw sheep milk undergoes less pH change. Protein aggregation was stopped by CP, which also supported a consistent microstructure.	[133]
Dielectric barrier discharge (DBD) reactor	180 and 300 s	Salmonella Typhimurium	NTP inactivates S. Typhimurium on solid agar surfaces by 1.1 log CFU log reduction as a surface cleaner on glass beads. NTP treatment on black peppercorns, a type of dry produce, used as real-life food product, shows a reduction in 0.3 log CFU/sample, moisture content, and quality were maintained after treatment. Pyruvate, vitamin C, and starch had no discernible impact on the NTP results.	[134]
Dielectric barrier discharge (DBD) gas plasma	10 and 60 min	Listeria monocytogenes	Water decontamination and disinfection can be accomplished by chlorine-free cold plasma. Microbial growth in fish processing water is inhibited by combining cold plasma with UVA irradiation. Synergy explained by photoactive species found in PAW. Food spoilage bacteria L. monocytogenes degraded by plasma-activated water and the food quality also retained.	[135]
Microbubble plasma generator	-	E. coli	PAW-generated microbubble plasma generator showed an effective antimicrobial against Escherichia coli. Highest antimicrobial activity PAW is 2.43  ±  1.02-log10 reduction.	[136]
Cold atmospheric pressure plasma (CAPP)	120 s	Staphylococcus aureus and Listeria monocytogenes	S. aureus and L. monocytogenes growth was effectively slowed down or even completely stopped by 120 sec CAPP treatments. Maximum reduction of 1–2 log cycle for both bacteria after 120 s exposure to CAPP CAPP has the ability to inactivate spoilage bacteria. CAPP may be able to reduce the number of bacteria on surfaces, but longer treatment times are required.	[137]

.

5. NTP Technology to Combat COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic known as COVID-19 has become a new global health crisis. It has halted economies in every nation it has impacted, with 200 million infections and more than 4.3 million deaths reported [23]. Plasmas are used in many different fields, primarily to modify the surfaces of solids, but they can also be used to eliminate microbes such as viruses. A biological method to measure the in vivo DNA damage brought on by bacteriophage lambda viruses exposed to air plasma was proposed by Yashuda et. al. ten years ago [138]. NTP has the benefit of being easily produced from air, water, and electricity, providing a sterilization solution at a lower cost without the cost and logistics of maintaining expensive and robust supply chains required for conventional methods that depend on necessities such as alcohol and hydrogen peroxide [139,140,141]. In order to effectively deactivate MS2 bacteriophages in aerosols while utilizing a minimal pressure drop across the reactor for air sterilization against airborne bacteriophages, Xia et. al. designed and constructed a packed-bed DBD plasma reactor. This procedure is effective at halting the airborne transmission of viral infections [142]. As several other researchers have discovered, NTP significantly increases the amount of protein oxidation that takes place in the viral capsid or coat. By producing ROS, NTP treatment puts bacteriophages into a dormant state. NTP operating parameters may favor viral DNA damage or protein inactivation, but further research is needed to confirm this. The mechanism for inactivating SARS-CoV-2 by using NTP is shown in Figure 8. The SARS-CoV-2 spike proteins bind to the ACE2 receptor during typical viral entry, allowing the virus to enter the host cell and replicate there. NTP caused damage to the spike proteins in SARS-CoV-2, which prevented the virus from attaching to the ACE2 receptor and preventing infection. However, NTP also causes DNA/RNA damage, which prevents SARS-CoV-2 from replicating. Additionally, plasma has been shown to alter exterior virus components necessary for attachment, such as the spike protein, and degrade pure SARS-CoV-2 RNA [28,29,143,144]. The NTP technology for viruses is still in its infancy and requires more research. More precise approaches are desperately needed to clarify which NTP particles are most important and how they affect viruses.

6. Applications of NTP for Environmental Protections

Controlling the dissipation of volatile organic compounds (VOCs) and hazardous contaminants from water is one of the most demanding environmental issues [145,146,147]. Long-term VOC exposure may result in a variety of illnesses, notably cancer, cardiovascular disease, and numerous other possible disorders [148]. Similarly, the presence of industrial effluents such as dyes and pharmaceutical waste in the aquatic system is a concern (threat) for the environment because of the fact of their nonbiodegradability, toxicity, and potential carcinogenic nature [149]. Therefore, controlling this environmental pollution has become an important issue and a hot research topic worldwide. Different technologies have been used for controlling these pollutants, including thermal and catalytic incineration [150], adsorption [151], condensation [152], coagulation [153], biofiltration [154], and membrane separation [155]. However, these kinds of treatments are often inefficient at removing pollutants such as pesticides, dyes, pharmaceutical compounds, and VOCs, which are increasingly present in the environment. Owing to this, advanced oxidation processes (AOPs) have been considered possible alternatives thanks to their extreme oxidizing capacity and their efficiency in the removal of bio-recalcitrant compounds [156]. Among these, NTP represents an innovative AOP for water treatment [157]. With respect to “thermal” plasma, the NTP system maintains at relatively low temperatures and is able to generate charge carriers. As reported in the literature, NTP technology is widely used for different applications and especially for the removal of pollutants from the environment [158]. It is well known that the NTP process could produce active species such as O₃, H₂O₂, ^•OH, and O^• which play a key role in the oxidative degradation of pollutants [159]. The start of the process is an important phase that remains poorly understood in the destruction of VOCs with low-temperature plasmas. A pioneering modeling work indicated that the radicals appear to be the dominant destruction species at low ethylene concentrations and low specific energy deposition (SED) values, whereas the metastable ones are found to be the dominant destruction species at high ethylene concentrations and high SED values. In addition to the reactions with radicals, the simulations study revealed that quenching reactions with metastable nitrogen N2 (equation image) appear to be an important process for the destruction of ethylene [160]. Atomic oxygen is the main destruction species in dry air at low SED and low ethylene concentrations, which are generally used for industrial uses [160]. For various ethylene concentrations, the effect of the SED on removal effectiveness and selectivity toward CO and CO2 was investigated. The presented model by a research group led by Aerts et. al. enables the identification of the pathway for destruction in both dry and humid air. The latter is found to be primarily initiated by metastable N₂ molecules, but O atoms and OH radicals dominate the subsequent stages of destruction [161]. However, some disadvantages of NTP “alone” in the degradation of organic contaminants are mostly associated with the creation of undesirable by-products, which might limit its industrial applicability. To circumvent these constraints, an intriguing technique combining NTP and heterogeneous catalysis has been proposed to improve pollutant degradation efficiency while simultaneously reducing the generation of reaction by-products [162]. The effect of NTP combined with catalysts enhances the generation of different types of active species (such as hydroxyls) and the activity and stability of catalytic materials [163].

6.1. Plasma Catalysis

Plasma catalysis is increasingly being used in a wide range of gas conversion processes, such as the conversion of CO₂ into high-value chemicals and fuels, the activation of CH₄ to form hydrogen, the generation of higher hydrocarbons or oxygenates, and the synthesis of NH₃ [164,165]. Other uses, such as those for reducing air pollution, such as the removal of VOCs, particulate matter, and NO_x, are already well-established [166]. Because the electron temperature is substantially higher than the temperature of the heavy species, radicals, and excited species are generated at temperatures closer to ambient in an NTP or non-equilibrium plasma (ions and neutrals). This nonthermal energy distribution has the ability to bypass the kinetic and thermodynamic constraints on the chemical conversion of reactants into desired products. If directed correctly, this energy can drive endothermic, equilibrium-limited processes under conditions when equilibrium conversions are negligible. Similarly, energy can accelerate reaction pathways that are kinetically slow under the current conditions [167,168,169]. The very energetic electrons in an NTP create (rotationally, vibrationally, and electrically) excited species, ions, and radicals through inelastic collisions with feedstock molecules, resulting in a multitude of novel species and states that are unreachable at bulk thermal temperatures. Because NTPs can contain a wide range of highly reactive species, it is difficult to operate them in a fashion that results in the generation of single products with high yield and selectivity. The integration of plasma and catalysts provides the possibility of combining the benefits of the two and permitting conversions that are now difficult [170,171]. The use of NTP in conjunction with heterogeneous catalysts is classified into two types based on the position of the catalyst: in-plasma catalysis (IPC) and post-plasma catalysis (PPC). The former is a two-stage method, where the catalyst is situated downstream of the plasma reactor, whereas the latter is a one-stage technique in which the catalyst is subjected to active plasma. The activation of the catalyst by NTP is linked to synergetic effects in plasma catalysis. All activation pathways include ozone, local heating, UV, the alteration of work function, lattice oxygen stimulation, adsorption/desorption, and electron–hole pair creation, as well as direct interactions among gas-phase radicals and adsorbed contaminants [166,170,172,173]. In a previous report, a thorough and in-depth explanation of plasma catalysts was presented [166].

For example, Yang et al. investigated NO_x degradation in a coaxial dual-dielectric barrier reactor using a mixed catalyst. It was discovered that the synthesized TiO_2x could accomplish significant degradation effects (84.84%, SIE = 401.27 J L1) in an oxygen-rich plasma catalytic system, outperforming TiO₂ (73.99%) and a single plasma degradation process (26.00%). The presence of Ti³⁺ and oxygen vacancies in TiO_2x caused a very narrow band gap, which helped to catalyze deeply the oxidation of NO_x to NO₂ and NO₃ during the plasma-induced "pseudo-photocatalysis" process. Meanwhile, TiO_2x increased the discharge current and efficiency, indicating its significant activating effect in the reaction. Reduced TiO_2x demonstrated a remarkable degrading effect in a long-term plasma-catalysis procedure while retaining its intrinsic crystal structure and morphology [174]. Capp et al. conducted a thorough investigation into the effects of combining titanium di-oxide (TiO₂) photocatalysts with nonthermal atmospheric pressure nitrogen–oxygen plasmas, which increased the production of ozone and dinitrogen pentoxide (N₂O₅) while limiting the formation of harmful nitrogen dioxide (NO₂) and nitrous oxide (N₂O) by-products. Magnetron sputtering was used to produce TiO₂ coatings atop barium titanate (BaTiO₃) particles for use in a packed-bed dielectric barrier discharge reactor (DBD). Titanium dioxide can influence plasma chemistry in the DBD by acting as a sink for atomic oxygen, catalyzing the generation of superoxide anion radicals (O₂⁻), and changing the dielectric constant of the BaTiO₃ particles. This study discusses the complicated interaction of these influences on the chemistry of oxygen and nitrogen plasmas. The effect of photocatalyst surface characteristics, gas composition, and residence duration on the reaction pathways for ozone and nitrogen oxide (N_xO_y) generation was studied. The photocatalytic activity of titanium dioxide was enhanced by annealing the coated surface, and it was later discovered to allow the synthesis of ozone, boost the formation of N₂O₅, and greatly decrease the formation of hazardous NO₂ and N₂O with a residence time of 0.011 s [175]. Plasma also has promising potential for catalyst synthesis and treatment. However, fuller knowledge of the underlying physical and chemical processes is required. Diagnostic experiments, studies into the physicochemical mechanisms underpinning plasma–catalyst interactions, and chemical activities occurring at the catalyst surface can all help to uncover this. The key problem is creating catalysts that are inexpensive, highly active, and stable while also being suitable for the plasma environment. It is impossible to overestimate the importance of understanding thermal, electrical, and photocatalysis.

6.2. Influence of NTP on the Catalytic Processes

6.2.1. The Properties of Catalyst

For catalyst preparation, NTP technology was employed. Plasma treatment improves the dispersal of active catalytic elements and alters the stability and catalytic activity of exposed catalyst material [176]. NTP can also change the oxidation state of the catalyst. In particular, when a Mn₂O₃ catalyst is exposed to a DBD plasma for an extended period of time, the occurrence of Mn₃O₄, a lower-valent manganese oxide with a strong oxidizing potential, is demonstrated by X-ray diffraction spectra [177]. After many hours of discharge operation, fewer parent Ti-O bonds are detected on TiO₂ surfaces owing to plasma–catalyst interactions [178]. Even new sorts of active sites with distinctive characteristics are being developed, such as persistent Al-O-O* with a lifespan of more than two weeks, as found in Al₂O₃ pores in IPC experiments, may emerge [179]. Plasma bombardment can cause a change in catalyst composition as well as an augmentation or reduction in specific surface area.

6.2.2. Adsorption

Adsorption processes are crucial in plasma–catalytic reaction systems [180]. If the catalyst has a high capacity for pollutant adsorption, the pollutant persistence duration in the reactor is extended. In the instance of IPC, the contaminant level in the discharge zone increases. The increased likelihood of collision between polluting molecules and active species improves the removal rate.

6.2.3. Plasma-Mediated Activation of Photocatalysts

Contaminants bind to the surface of porous semiconductors, which are subjected to UV light in photocatalytic activity. UV photons form electron–hole pairs, causing the adsorbed contaminant to be oxidized by valence band holes. The oxidation products are finally desorbed. TiO₂ is one of the most effective photocatalysts (together with ZnO, ZnS, CdS, Fe₂O₃, and WO₃) for the breakdown of a wide spectrum of organic pollutants. The surfactant-assisted sol–gel technique was combined with microwave plasma calcination to produce TiO₂ nanopowders. To reduce calcination time and ensure energy-efficient photocatalyst production, plasma calcination was performed for only 20–30 min. Under these conditions, mixed anatase-rutile phased TiO₂ nanoparticles were produced. Microwave plasma calcination reduced the photocatalyst’s band gap energy by 40%. Surfactants were discovered to be ineffective in phase transitions of synthetic TiO₂. The absorption of the O-Ti-O band spanning between 415 and 420 cm⁻¹ was confirmed by FTIR analysis. After plasma calcination, the hydroxyl bands (OH) were found to be less stretched. The band gap energies of the normally calcined HA-Ti, NA-Ti, and MS-Ti samples were 5.09 eV, 4.88 eV, and 5.06 eV, respectively. The band gap energies of plasma-calcined MTHA-Ti, MTNNA-Ti, and MTMS-Ti samples were calculated to be approximately 4.92 eV, 3.11 eV, and 4.96 eV, respectively. The combined effect of photocatalyst, plasma reactive species, and UV radiation increased the efficiency of methylene blue dye degradation. After 30 min of DC plasma jet exposure, the maximum degradation efficiency of 95% was attained. After four dye degradation cycles, the catalyst preserved approximately 93–95% degradation efficiency [181].

A DBD reactor with BaTiO₃ and TiO₂ photocatalysts was used to examine plasma-photocatalytic CO₂ conversion into CO and O₂. The combination of plasma with the BaTiO₃ and TiO₂ photocatalysts in the CO₂ DBD slightly increases the gas temperature of the plasma by 6–11 °C compared to the CO₂ discharge in the absence of a catalyst at an SED of 28 kJ/L, while the plasma gas temperature in the gas phase is almost the same as the temperature on the surface of the photocatalysts (BaTiO₃ and TiO₂) in the plasma-catalytic DBD reactor. The combination of plasma with BaTiO₃ and TiO₂ catalysts has a synergistic impact that increases CO₂ conversion and energy efficiency by a factor of 2.5 when compared to the plasma reaction without a catalyst. The presence of catalyst pellets in the plasma gap is found to play a dominant role in inducing plasma’s physical effects such as the enhancement of the electric field and the production of more energetic electrons and reactive species, which leads to chemical effects and contributes to CO₂ conversion. We discovered that the intensity of UV emissions produced by the CO₂ DBD is much lower than that emitted by external UV sources (e.g., UV lamps), which are routinely utilized to activate photocatalysts in conventional photocatalytic reactions. This phenomenon implies that the UV emissions produced by the CO₂ DBD play only a minor role in the activation of the BaTiO₃ and TiO₂ catalysts in the plasma-photocatalytic conversion of CO₂ and that their contribution to the exceptional performance of the plasma-photocatalytic reaction and the synergy of plasma photocatalysis could be very weak or negligible [182]. When a TiO₂-based photocatalyst is combined with a nonthermal plasma, various synergistic effects occur that are not all related to photocatalytic mechanisms. To gain a comprehensive knowledge of plasma/TiO₂ synergy, at least four effects must be distinguished: (1) TiO₂ catalytic material enhances injected energy for the same applied voltage due to quicker filament breaking, most likely due to a larger amount of adsorbed charges and a bigger local electric field due to TiO₂’s high permittivity. (2) TiO₂ may alter the breakdown mechanisms of filaments with the same supplied energy. The porosity of the catalytic material boosts the effectiveness of reactions triggered by plasma species, most likely due to improved contact between reagents when they are adsorbed. If TiO₂ is sufficiently activated, increased photocatalytic reactivity involving electron–hole pairs of TiO₂ may occur in interaction with the plasma phase [183].

6.2.4. Thermal Activation

Despite gas heating raising catalyst surface temperatures, the heating impact is often insufficient to compensate for the thermal activation of the catalyst. Hot spots can emerge in packed-bed reactors; however, adapted heating is driven by powerful microdischarges running between the sharp edges and corners of neighboring pellets. Catalytic VOC elimination can be aided by increasing catalyst temperatures [184]. A low-temperature plasma reactor is used for the plasma-catalytic conversion of CO₂. Combining plasma plus a catalyst is an active technique to obtain high conversion rates while consuming little energy. TiO₂ is a common catalyst used in dielectric barrier discharges. According to Guaitella et al., the plasma–photocatalyst synergy provides enhanced conversions and energy efficiency. This research distinguishes three key synergistic effects: (a) the influence of catalysts on power input; (b) the effect of porosity on C₂H₂ oxidation; and (c) the photocatalytic degradation of C₂H₂ on TiO₂ during plasma exposure. According to reports, the presence of glass fibers enhances the injected power at a constant voltage substantially. Glass fiber macroporosity and nanoparticles both play small roles in C₂H₂ oxidation enhancement. The generation of O atoms near the surface is most likely responsible for the increased removal efficiency of C₂H₂ from porous material [183]. Mei et al. developed a coaxial DBD reactor for the atmospheric pressure and low-temperature plasma-catalytic conversion of pure CO₂ into CO and O₂. According to the findings, the synergy between the plasma and the photocatalyst improves energy efficiency and conversion rates. A plasma-driven photocatalytic process aids in CO₂ conversion [182].

7. NTP for Catalytic VOCs Abatement

Controlling VOC emissions from anthropogenic sources has emerged as a critical issue in environmental protection as a result of growing global awareness. One of the most promising methods for the handling of VOCs is nonthermal plasma catalysis, which has high efficiency, good by-product selectivity, and superior carbon balancing (VOCs) [185]. For example, Hoseini et al. synthesized a Mn₂O₃ catalyst from a spent alkaline battery using a hydrometallurgical technique. Manganese oxide was impregnated at various percentages on alumina and utilized as a catalyst for the oxidation of benzene, toluene, and xylene (BTX) in a hybrid plasma–catalytic process. Whereas MnAl catalysts produced a comparable benzene and toluene oxidation percentage (97–98%), xylene oxidation was problematic and dependent on the Mn percent, so the catalyst with 10% wt. of manganese oxide indicated 74% of xylene oxidation while higher or lower Mn contents exhibited lower oxidation percent. The effect of the plasma input voltage, the catalyst position in the plasma reactor, the BTX flow rate, and the catalyst loadings on the experimental parameters was examined. The results revealed that benzene and toluene were practically totally oxidized regardless of the input plasma voltage, whereas the percentage of xylene oxidation increased as the voltage was increased. Furthermore, the position of the catalyst in the reactor had no effect on BTX conversion; however, increasing the flow rate resulted in a decrease in BTX removal efficiency [177]. We discussed this section in detail and divided them into the three most investigated target chemicals, namely, trichloroethylene, benzene, and toluene.

7.1. Trichloroethylene

Chlorinated VOCs (CVOCs) are often present in industrial waste gases because they are extensively used as chemicals and solvents in industry. Because of its diverse range of solvent uses and degreaser in industry, trichloroethylene is perhaps the most prevalent CVOC discharged into the atmosphere. However, the International Agency of Cancer (IARC) reports that TCE is carcinogenic to humans, suggesting that its atmospheric emission must be prohibited to protect public health [186]. The performance of TCE decomposition for TiO₂ catalysts has been examined by Oda et al. in relation to the initial TCE concentration, pellet size, and sintering temperature. The breakdown voltage to produce NTP is significantly lower when the barrier-type reactor is filled with TiO₂ sintered at 673 K as compared to when the reactor is empty and when the reactor is filled with TiO₂ sintered at 1373 K. According to their hypothesis, the disk-shaped dielectric pellets sintered at 673 K had a non-uniform geometrical distribution that disrupted the electric field and produced an electric field concentration at the pellets’ contacting region. This result suggests that contacting point discharges or surface discharges occur on the surfaces of the pellets, lowering the breakdown voltage and increasing the decomposition energy efficiency. Additionally, they show that too-fine TiO₂ particles disrupt the gas flow and result in insufficient plasma filling of the discharge area [187].

Han et al. have further investigated the direct and indirect processes’ effects of the manganese dioxide post-plasma catalyst. For the direct process, oxygen species mostly convert TCE into DCAC when excited species (or electrons) collide with O₂. The improved decomposition efficiency for the direct procedure is attributed to the oxygen species formed during ozone breakdown at the surface of MnO₂ oxidizing the continuing TCE into trichloroacetaldehyde (CCl₃-CHO, TCAA). At an energy density of 120 J/L, the CO_x production increases from 15% to 35% when MnO₂ is present. Increasing the energy density to 400 J/L results in a CO_x yield of 98%. Similar results are found for the indirect approach, even if the CO_x yield is not as good [188]. The degradation of trichloroethylene (TCE) in dry air was examined using a multi-pin-to-plate mixed negative DC corona/glow discharge with the MnO₂ catalyst positioned downstream of the plasma reactor [189]. The activation energy for the plasma-catalytic system was much lower (1.5 kcal/mol) than it was for the pure catalytic system (8.7 kcal/mol), indicating that the oxygenated intermediates created by the plasma are more favorable to catalytic oxidation than TCE (Figure 9). Compared to the separate systems, the combined application of plasma and catalysis enhanced TCE abatement. To begin, electron–molecule collisions transform N₂ and O₂ molecules into a complex mixture of ionized, excited, radical, and metastable species capable of decomposing TCE into oxygenated intermediates and ultimate oxidation products. Second, in the gas phase, ozone dissociates on the catalyst surface to generate peroxide groups and molecular oxygen. These surface species accelerate TCE oxidation to CO, CO₂, HCl, and Cl₂. This oxidation is more efficient if oxygenated molecules, such as phosgene and DCAC, reach the catalyst’s surface. A summary of the plasma-catalytic TCE abatement provided in

Table 3. Summary of the plasma-catalytic TCE abatement.

Plasma Type	Catalyst	Position	Flow Rate	Concentration	$\mathit{\eta } \left(\%\right)$	Ref.
DDBD	BaTiO3	PPC	1000 mL/min	100 ppm	100	[157]
DBD	MnO2	PPC	500 mL/min	250 ppm	99	[189]
CD	Pd/LaMnO3	PPC	2000 mL/min	500 ppm	81	[190]
CD	Cu-Mn oxide	PPC	500 mL/min	300 ppm	56	[191]
CD	CeMnO	PPC	2000 mL/min	400 ppm	87	[192]
DBD	MnO2	PPC	500 mL/min	250 ppm	99	[188]
DBD	TiO2	IPC	400 mL/min	100 ppm	99	[187]
DBD	CoMnOx/ZSM-5	IPC	1 L/min	-	94	[193]
DBD	TCAD, C2HCl3O	IPC	400 mL/min	300 ppm	59	[194]
NTP reactor	Ag-Mn-Ce/HZSM-5	PPC	1 L/min	300 ppm	100	[195]

.

7.2. Benzene

Various catalyst formulations and reactor designs have been reported by various research groups to improve the degradation of benzene with NTP. Jiang et al., for instance, used an optimized surface/packed-bed hybrid discharge (SPBHD) plasma in combination with MO_x (M = Ag, Mn, Cu, or Fe) catalysts in a post-plasma-catalysis (PPC) system to accomplish the degradation of benzene [196]. When plasma was combined with all MO_x/Al₂O₃ catalysts, the benzene degrading was strengthened, and the mineralization phase was considerably accelerated toward total oxidation. The same group has used in-plasma catalysis (IPC) and post-plasma catalysis (PPC) configurations of plasma-assisted catalysis to degrade benzene via hybrid surface/packed-bed discharge (HSPBD) plasmas over a sequence of Ag_x Ce_1-x/-Al₂O₃ catalysts (Figure 10a). The plasma and Ag_x Ce_1-x/-Al₂O₃ catalyst combination considerably increased the reaction performance when compared to the plasma-only process, and the combined degradation efficiency is a synergistic impact rather than primarily an additive effect. Both benzene molecules and intermediates formed by direct plasma reactions can be adsorbed on the catalyst surface in a PPC arrangement where the Ag_0.9Ce_0.1/-Al₂O₃ catalyst is placed downstream of area II. Following that, active oxygen species created on the catalyst surface via surface reactions can primarily oxidize benzene and intermediate molecules into CO₂ and H₂O, while the resulting oxygen vacancies can be replaced by gas phase oxygen and active oxygen species generated in the NTP process. As a rate-determining step, the alternate oxidation and reduction processes of metal active sites on the catalyst surface provide a continual supply of active oxygen species [197]. LaMnO₃ and OMS-2 catalysts were used in a plasma-catalytic reactor for the study of chlorobenzene removal (Figure 10b). The combination of NTP and manganese-based catalyst significantly improved CB removal efficiency, CO₂ selectivity, and energy efficiency when compared to NTP alone. Meanwhile, the use of a catalyst can considerably lower O₃ and NO_x production while also preventing the development of byproducts. The OMS-2 catalyst outperformed the LaMnO₃ catalyst in terms of activity, with a maximum CB removal efficiency of 89.5% and a CO₂ selectivity of 57.6%. More than 15 byproducts were discovered in the NTP reactors, with nitrogenous organic molecules (intermediate A) being detected in the NTP reactor without a catalyst. This was mostly owing to manganese-based catalysts boosting partial particle energy above the nitrogen-to-nitrogen triple bond dissociation energy (9.8 eV).

Many different types of small molecules were found in the NTP reactor with OMS-2, including oxalic acid (intermediate C), 2-pentanone (intermediate D), sec-pentanol (intermediate E), glycerol (intermediate F), valeric acid (intermediate G), and ethylene glycol (intermediate H). As a result, the inclusion of a manganese-based catalyst to the deep oxidation reaction intermediate reduced the development of hazardous byproducts. Overall, the OMS-2 catalyst was more favorable for CB mineralization than the typical NTP reactor and the NTP with LaMnO₃ reactor, which promoted deep oxidation and reduced by-product generation. Based on the results of the preceding investigation, the OMS-2 catalyst with the best catalytic effect was chosen, and three different reaction routes were proposed. In the first route, a series of active species (such as O•, HO•, and HO₂•) and high-energetic electrons in the plasma-catalytic system could attack CB, and subsequently, dechlorination occurred through the substitution and ionization reactions, and benzene (intermediate I) and phenol(intermediate J) was generated. The benzene ring was then opened by high-energy molecules, resulting in a sequence of alkanes (intermediate E), organic acids (intermediate C, G), and alcohols (intermediate F, H) that were eventually degraded to CO₂, H₂O, and HCl. For the second reaction pathway, high-energy electrons bombarded the C-H bond to cause the de-H reaction, and then a reaction with HO• occurred to form O-chlorophenol (intermediate B). Under the action of free radicals and electrons, O-chlorophenol is replaced by dechlorinated carboxyl groups to generate salicylic acid (intermediate O), or the benzene ring is opened and substituted to form an alcohol (intermediate H) to form salicylic acid, eventually creating CO₂, H₂O, and HCl. The third method involved converting CB to benzoic acid (intermediate K). Benzoic acid performed a sequence of complex chemical reactions to generate a series of alkanes and organic acids before decomposing into CO₂, H₂O, and HCl [198].

The breakdown of gas-phase benzene was studied by Kim et al. utilizing plasma-driven catalyst (PDC) reactors filled with TiO₂, Pt/TiO₂, or Ag/TiO₂. For a comparison study, a standard BaTiO₃ packed-bed plasma reactor was also used. Compared to those using the traditional BaTiO₃ packed-bed plasma reactor, the PDC reactors were shown to be more effective in terms of energy efficiency and the elimination of undesired reaction products. The test materials’ catalytic activity for the breakdown of benzene went in the following order: Ag/TiO₂, TiO₂, and Pt/TiO₂. Additionally, it was discovered that a silver (Ag) catalyst improved the CO₂ [199]. Lee et al. used hybrid systems of discharge plasma and photocatalysts to carry out the breakdown of gas-phase benzene. By suppressing secondary products, a hybrid plasma–photocatalyst system improved CO₂ selectivity. It was crucial to use a high-porosity material for the hybrid system in order to maximize CO₂ selectivity. For this, benzene conversion and selectivity to CO₂ were significantly improved when utilizing Al₂O₃ as a catalytic support [200].

Table 4. Summary of the plasma-catalytic benzene abatement.

Plasma Type	Catalyst	Position	Flow Rate	Concentration	$\mathit{\eta } \left(\%\right)$	Ref.
DBD	AgO/Al2O3	PPC	800 mL/min	116 ppm	77	[196]
DBD	AgxCey/Al2O3	PPC	500 mL/min	400 ppm	65	[197]
Packed-bed DBD	TiO2	IPC	1000 mL/min	210 ppm	82	[199]
DBD	TiO2	IPC	100 mL/min	100 ppm	60	[201]
DBD	Ag/TiO2	IPC	4000 mL/min	110 ppm	99	[202]
DBD glow discharge	TiO2/Al2O3	IPC	200 mL/min	100 ppm	50	[200]
Pulsed corona	Silica gel	IPC	100 mL/min	300 ppm	85	[203]
Surface discharge	Ag/TiO2	IPC	3000 mL/min	200 ppm	99	[204]
DBD	Ni-γAl2O3	IPC	100 mL/min	70–190 g/Nm3	92.31	[205]
DBD	La-NiOx	IPC	100 mL/min	430 ± 10 ppm	50	[206]
DBD	Co2Ni1Ox	IPC and PPC	100 mL/min	100 ppm	99	[207]
DBD	CO/CO2	IPC	100 mL/min	350 ppm	93.7	[208]
DBD	CuO, ZnO, Fe3O4	IPC	500 mL/min	235 ppm	94.9	[209]

provides a brief overview of the plasma-catalytic benzene abatement.

7.3. Toluene

The catalytic process based on NTP has been widely researched for toluene reduction. Some of the important papers are explained briefly. By oxidizing toluene in a dielectric barrier discharge (DBD) reactor, X. Xu et al. assessed the catalysts’ NTP catalytic performance. The findings revealed that Co-MCM-41 and Co-MCM-41 imp have different levels of catalytic activity and stability. The well-dispersed cobalt species, strong ozone decomposition activities, and high capacity to break down organic intermediates on catalyst surfaces were identified as the key causes of the improved catalytic performance and stability [210]. In an attempt to apply Ag-Mn/-Al₂O₃ materials for the removal of toluene through an adsorption plasma-catalytic process, Qin et al. investigated the effects of changing the sequence in which Ag and Mn were impregnated. The results demonstrate that related to the co-impregnated catalyst Ag-Mn-C/-Al₂O₃, the catalyst with Ag first impregnated Ag(F)-Mn/-Al₂O₃, and bare -Al₂O₃, Mn was attached first (Ag-Mn(F)/-Al₂O₃), and the catalyst had a longer breakthrough time, lower emission of toluene, and improved carbon balance [211]. W. Xu et al. used a series of Ni-SBA catalysts in conjunction with an adsorption–discharge plasma system to catalyze the removal of low concentrations of toluene. The outcomes revealed that after 60 min of plasma catalysis, the 5% Ni-SBA sample had a greater toluene mineralization rate (71.8%) than the other samples [212]. Next, a single-stage coaxial DBD reactor was implemented to compare the simultaneous removal of toluene and styrene under NTP and NTP catalysis (Figure 11a,b). To better understand the mechanism of degradation and the consequences of coexistence, the effects of VOC mixture, humidity, materials filling in the discharge zoon, removal efficiency, CO_x selectivity, and by-product types and emission levels were thoroughly explored. According to experimental findings, when treated with styrene during plasma treatment, toluene elimination was severely impeded. However, under the same circumstances, styrene was little impacted. It was discovered that the conversion of toluene was constrained by benzaldehyde, which served as the main organic waste from styrene and consumed the oxidizing particles (O and OH) [213]. The decomposition of toluene in a dielectric barrier discharge (DBD) reactor with a number of CeO₂-MnO_x catalysts was studied by Wang et al. (Figure 11c). The plasma-catalytic system greatly enhances the removal of toluene when compared to the NTP alone approach, and CeO₂-MnO_x catalysts outperform pure CeO₂ and MnO_x catalysts in terms of catalytic performance. With an input power of 24 W, the Ce1Mn1 catalyst achieves the maximum CO₂ selectivity and removal efficiency, which are 95.94% and 90.73%, respectively. C-H in the methyl group has the lowest dissociation energy (3.7 eV), followed by C-H in the benzene ring (4.3 eV), C-C in the coupled methyl group with the benzene ring (4.4 eV), C-C in the benzene ring (5.0–5.3 eV), and C = C in the benzene ring (5.0–5.3 eV) (5.5 eV).

Thus, the easiest process in toluene decomposition is the destruction of C-H outside the benzene ring, which results in the creation of the benzyl radical. Benzaldehyde and benzyl alcohol can be formed via the reaction between the benzyl radical and O. Furthermore, phenyl produced by breaking a C–C bond can react with H•, CH₃•, and OH• to form benzene, o-xylene, and phenol separately. Meanwhile, the ring-containing intermediate products can couple to form a polymer compound. A series of active species (O•, OH•, H•) and high energetic electrons (>5.5 eV) can attack the benzene ring to generate ring-opening products. These chain intermediates are oxidized to CO₂ and H₂O and then to toluene. Intermediates and reactive species in the gas phase are adsorbed onto the surface of catalysts, where they are oxidized further by active surface oxygen species. As a result, oxygen atom species are critical in the breakdown of toluene on the surface of catalysts. Interactions between MnO_x and CeO₂ can increase oxygen mobility on the catalysts and speed up the formation of active oxygen species. This active atomic oxygen generated by the catalyst, plasma, and O₃ may significantly improve toluene removal efficiency and CO₂ selectivity [214]. Additionally, using a simple in situ Ce doping technique, a series of Ba1_xCe_xTiO₃ perovskite catalysts with high specific surface areas (68.6–85.6 m² g⁻¹) were developed and evaluated for their ability to catalytically degrade toluene (Figure 11d). The catalysts and nonthermal plasma worked in cooperation to generate a powerful result. When BC₄T (Ce/Ti molar ratio = 4:100) was packed in a coaxial dielectric barrier discharge reactor at a specific input energy of 508 J L⁻¹, the results showed the maximum decomposition efficiency (100%), CO_x selectivity (98.1%), and CO₂ selectivity (63.9%), and the lowest O₃ generation (0 ppm). The C-H in the methyl group was destroyed by high-energy electrons to generate a benzyl group because it had the lowest dissociation energy in toluene. The benzyl group was structurally unstable, and it reacted with oxygen species (such as ^•O and ^•OH) to produce benzaldehyde and phenylmethanol. Because benzaldehyde and phenylmethanol polymerized with methyl formate, respectively, methyl benzoylformate and -hydroxy-methyl ester-benzeneacetic acid were identified. In a DBD-catalytic reactor, the plasma catalytic performance of toluene decomposition over various transition metal-supported catalysts was assessed recently [215]. At room temperature, the toluene decomposition and energy efficiency were highest for γ-Al₂O₃ supported with 1 wt% MnO₂. The ability of catalysts to decompose O3 was correlated with the efficiency of toluene decomposition. According to the results of the study, 1 wt% Mn/γ-Al₂O₃ was better at catalyzing the conversion of toluene to carbonate and bicarbonate via the breaking of C-C bonds from benzoic acid [215]. Recent studies have looked at the plasma-catalyzed CO₂ hydrogenation over ZnO and Pd/ZnO using a tabular DBD reactor at low temperatures. With the help of online mass spectroscopy (MS), optical emission spectroscopy (OES) diagnostics, and a newly developed integrated DBD/FTIR gas cell reactor, it may be possible to better understand the mechanisms and pathways of complex plasma-catalyzed chemical reactions, particularly plasma-assisted surface reactions [216]. In a recent study, the effects of surface temperature and plasma irradiation on catalyst surfaces were also assessed. The concentration of adsorbed species decreased as the catalyst surface temperature increased, promoting desorption and gas-phase ammonia production [217]. The experimental confirmation of surface reactions involving plasma-activated intermediates should serve as a guide for establishing more precise descriptions of the steps in plasma-activated catalytic ammonia synthesis [217].

Figure 11. (a) Summary of suggested degradation pathways and NTP system effect on the simultaneous removal of binary VOCs mixture. (b) Comparison of quartz sand and catalyst filling on VOCs’ removal efficiency of toluene. Reaction conditions: toluene (styrene): 50 ppm, air as carrier gas, and GHSV of 60,000 mL·(g·h)⁻¹. Reused with permission from [213]. Copyright 2021, Elsevier. (c) Plausible reaction pathway for the plasma-catalytic Ttoluene abatement. Reused with permission from [214]. Copyright 2016, Elsevier. (d) Schematic diagram of the plasma-catalytic decomposition of toluene. Reprinted with permission from Ref. [218]. Copyright 2021, Elsevier.

Figure 11. (a) Summary of suggested degradation pathways and NTP system effect on the simultaneous removal of binary VOCs mixture. (b) Comparison of quartz sand and catalyst filling on VOCs’ removal efficiency of toluene. Reaction conditions: toluene (styrene): 50 ppm, air as carrier gas, and GHSV of 60,000 mL·(g·h)⁻¹. Reused with permission from [213]. Copyright 2021, Elsevier. (c) Plausible reaction pathway for the plasma-catalytic Ttoluene abatement. Reused with permission from [214]. Copyright 2016, Elsevier. (d) Schematic diagram of the plasma-catalytic decomposition of toluene. Reprinted with permission from Ref. [218]. Copyright 2021, Elsevier.

Furthermore, the plasma-generated species easily dissolved the C-C link connecting the methyl group and the benzene ring to form a phenyl group, which reacted with •N₂O and •CH₃ to form nitrobenzene and mesitylene, respectively. A considerable quantity of ROS were created on the catalyst surface in our plasma-catalytic hybrid system, which successfully promoted intermediate degradation. The majority of the intermediates were oxidized to CO₂ and H₂O [218]. A brief summary of the plasma-catalytic toluene abatement is provided in

Table 5. Summary of the plasma-catalytic toluene abatement.

Plasma Type	Catalyst	Position	Flow Rate	Concentration	$\mathit{\eta } \left(\%\right)$	Ref.
DDBD	BaTiO3	IPC	1000 mL/min	100 ppm	100	[157]
DBD	Co-MCM-41	IPC	200 mL/min	100 ppm	100	[210]
DBD	Ag-Mn (F)/Al2O3	IPC	2000 mL/min	400 ppm	100	[219]
DBD	Ag-Mn/HZSM-5	IPC and PPC	3000 mL/min	3 ppm	93	[211]
DBD	CeO2-MnOx (Ce1Mn1)	IPC	130 mL/min	500 ppm	96	[214]
DBD	MnOx/SMF	IPC	500 mL/min	100 ppm	100	[220]
DBD	Ni-SBA	CSD	100 mL/min	50 ppm	71	[212]
DBD	Ca-Ni/ZSM-5	IPC	100 mL/min	100 ppm	90	[221]
DBD	MnO2/GFF	PPC	250 mL/min	260 ppm	93	[222]
DBD	α-MnO2	PPC	500 mL/min	145 ppm	100	[223]
DBD	Ti-Co	PPC	-	100 mg/m3	72	[224]
DBD	Mn–Fe/rGO	IPC	225–425 L/h	657.14 mg/m3	85.6	[225]
DBD	SiO2/Al2O3	IPC	75 mL/min	45 ppm	85	[226]

.

8. Nonthermal Plasma Coupled with Catalyst for the Degradation of Water Pollutants

One of the most promising technologies for degrading dangerous contaminants in wastewater is nonthermal plasma. Recent research has shown that different operating parameters have an impact on the yield of processes based on nonthermal plasma (NTP). In particular, a catalyst that is properly positioned in the NTP reactor causes a considerable improvement in process performance compared to NTP alone. Several studies have been carried out to evaluate the potential of NTP in conjunction with catalysts for the removal of various types of pollutants in an aqueous solution. It is obvious that defining an ideal situation that can work for all forms of pollutants and the many kinds of catalysts utilized in this situation is still difficult. However, it was clearly explained that the operational factors are crucial. However, it is often challenging to understand how plasma can affect the catalyst and the generation of the oxidizing species most in charge of degrading pollutants. The purpose of this review is to offer an insight into catalytic compositions used in conjunction with NTP technology to remove water contaminants. Specifically, the reactor architecture to be used when NTP was coupled with a catalyst, the placement of the catalyst in the reactor, and the function of the primary oxidizing species were provided.

8.1. Decontamination of Pharmaceutical Compounds

Drug usage has recently increased the variety of toxins entering the environment. Different pharmaceutical chemicals do not completely degrade during wastewater treatment operations due to their low biodegradability and strong chemical stability. According to reports, the combination of NTP and a catalyst is a viable technique for removing pharmaceutical pollutants from wastewater. For instance, Guo et al. created a hybrid rGO-TiO₂ nanocomposite for the PDP system’s synergetic degradation of fluoroquinolones (Figure 12). According to the degrading performance testing, the composite has the best catalytic performance, with a 99.4% elimination efficiency in the PDP system, which is better than the 64.8% in the solitary PDP system [227].

In order to degrade aqueous amoxicillin in plasma, Ansari et al. produced ZnO and -Fe₂O₃ as a nanocatalyst (ZnO/-Fe₂O₃) and paired it with DBD (AMX). According to the results, the AMX degradation was greatly boosted by the ZnO/-Fe₂O₃ composite catalyst, going from 75.0% (when employing a single plasma reactor) to 99.3% under ideal conditions [228]. Another recent study examined how DBD in conjunction with Bi₂WO₆-rMoS₂ could degrade sulfamethoxazole (SMZ) in wastewater. The combined effect of the DBD plasma reactor and Bi₂WO₆-rMoS₂ nanocomposites significantly increased the degradation efficiency of the antibacterial medication (97.6% vs. 72.5%). Ozone and hydrogen peroxide were utilized as indirect indicators of the generation of the •OH radicals by the authors to analyze the impact of oxidizing species in this work [229]. Triclocarban (TCC) was reported to degrade in water using a dielectric barrier discharge plasma in conjunction with TiO₂-activated carbon fibers by Wang et al. (ACFs). The degradation of triclosan (TCS) from pharmaceuticals and personal care products followed a very similar procedure. In this case, a DBD reactor and activated carbon fibers are provided using this method. In this study, the electric discharge creates plasma that can be used to synthesize ACFs in situ and reuse them for additional treatment cycles in addition to degrading TCS [230].

Table 6. Summary of the main operating conditions and catalysts used for the degradation of pharmaceutical compounds in aqueous phase by NTP coupled with catalysts.

Pollutants	Plasma Type	Type of Catalyst	Degradation(%)	Degradation Time	Ref.
Fluoroquinolone	PDP	Graphene-TiO2	93	60 min	[227]
Triclosan	DBD	ACFs	93	18 min	[231]
Levofloxacin	DBD	Ag3PO4/ACFs	93	18 min	[232]
Enrofloxacin	PDP	Graphene-WO3	99	60 min	[185]
Amoxicillin	DBD	ZnO/Fe2O3	99	18 min	[228]
Chloramphenicol	PDP	TiO3/WO3	88	60 min	[233]
Acetaminophen	DBD	TiO2-rGO	92	18 min	[234]
Sulfamethoxazole	DBD	Bi2WO6-MoS2	98	21 min	[229]
Triclocarban	DBD	TiO2/ACFs	64	30 min	[230]
Ketoprofen	DBD	TiO2	99	10 min	[235]
Sulfamethoxazole	DBD	ZrO2/CeO2	90	90 min	[162]
Sulfadiazine	DBD	Fenton	99	30 min	[236]
Irgarol 1051	DBD	TiO2	99	240 min	[237]
Tetracycline	DBD	Mn/Al2O3	99	40 min	[238]

summarizes the primary operating conditions and catalysts employed for the degradation of pharmaceutical compounds in aqueous phase by NTP coupled with catalysts.

8.2. Removal of Dyes

One of the most prominent pollutant groups in wastewater from textile and other industrial processes is composed of organic dyes. Because the dyes may be poisonous and are visible in surface waterways, the removal of this type of pollutant from wastewater is a significant issue from an environmental perspective. A method that looks promising for the degradation of this kind of pollutant is the combination of NTP and a catalyst. Numerous studies proving the effectiveness of the procedure are described in the literature. The effectiveness of NTP (DBD reactor) in conjunction with g-C₃N₄/TiO₂ for the degradation of the acid orange 7 dye in an aqueous solution was reported by Liu’s research group (Figure 13) [239].

Guo et al. also report on the AO₇ degradation, demonstrating the use of activated carbon and pulsed discharge plasma (PDP) (AC). Due to the AC’s adsorbent and catalytic properties, its presence in the PDP/AC combination helps to provide a synergistic effect. The creation of the OH^• and O^• radicals was investigated in particular as it relates to the impact of AC addition on the production of activated species [240]. Zhang et al. suggested using activated carbon fibers along with TiO₂ for the application. In particular, they describe how to employ a PDP reactor with activated carbon fiber loaded with TiO₂ to degrade methyl orange (MO) in an aqueous solution [241]. Iervolino et al. reported degrading acid orange 7 dye (AO₇) in an aqueous solution utilizing immobilized Fe₂O₃ on glass spheres as a catalyst in a DBD reactor. The authors demonstrate that using catalytic packed material enables the total degradation of AO₇ pollutant to be achieved in a relatively short amount of time (~10 min) with the supplied voltage of 12 kV, which is below that typically employed for this technique [242].

Table 7. A summary of the key operating conditions and catalyst utilized for the degradation of dyes in aqueous phase by NTP combined with a catalyst.

Pollutants	Plasma Type	Type of Catalyst	Degradation(%)	Degradation Time	Ref.
Methyl Orange	PDP	ACF/TiO2	98	15 min	[241]
Crystal violet	DBD	BiPO4	91	12 min	[243]
Acid Orange 7	DBD	C3N4/TiO4	100	12 min	[239]
Reactive Yellow	DBD	TiO2	83	180 min	[244]
Acid Orange	DBD	Fe2O3	80	5 min	[242]
Orange G	GAD	Laterite soil	100	60 min	[245]
Acid Orange 7	PDP	Activated carbon	83	60 min	[240]
Acid Orange 7	DBD	CeO2/γ-Al2O3	84	30 min	[246]
Orange G	Water surface plasma (WSP)	Bi2O3/CaFe2O4	28.9	-	[247]
Brilliant Blue R	Atmospheric plasma discharge	PVDF/MWCNTs	94	20 min	[248]
Acid Black 52	Air plasma	-	96.15	200 min	[249]
Alizarine reds of stimulated (ARS)	Gas-liquid two-phase discharge plasma	-	94.6	60 min	[250]

provides a concise overview of the operating conditions and catalysts utilized for the degradation of dyes in aqueous phase by NTP.

Additionally, DBD combined with BiPO₄ has been found to degrade the crystal violet dye in an aqueous solution. The CV dye was not shown to be adsorbed by this catalyst, but it does participate in the photogeneration of reactive species. In fact, its inclusion in the DBD reactor enabled the dye’s degradation to increase by up to 28% after 12 min of exposure [243]. Furthermore, it has been noticed in this circumstance that an increase in input power improves dye degradation up to a particular power value, after which, a reduction in the dye’s degradation efficiency was observed.

9. Concluding Remarks

NTP application in medicine has grown from a concept, inspired by plasma physicists, to an interdisciplinary research area with increasing acceptance in the medical industry. The use of NTP for therapeutic purposes can be used to achieve a variety of medical objectives, including the decontamination of wounds and skin, the promotion of wound healing, the suppression of cancer, the management of multi-drug resistant bacteria that reside in wounds, and dental and aesthetic procedures. However, it is crucial to recognize and take advantage of the special benefits of plasma therapies in comparison to other forms of treatment [23]. A cutting-edge strategy is the formation of reactive species using NTP sources. These reactive species played a vital role in anticancer and various medical applications. To date, many studies (in vivo and in vitro) have shown that NTP has the potential to suppress cancer/tumors without harming healthy cells (Table 1) [23]. Preclinical and clinical trials should be carried out and assessed so that the interactions between plasma and biological cells and tissues can be fully understood.

Additionally, NTP technology has been used extensively in the food industry for the past few decades to sterilize food to keep it fresh and increase its storage life. Table 2 provides a summary of recent developments on this research topic along with some important findings. It is clear that food intrinsic factors must be taken into consideration when developing a plasma treatment because they affect the cell inactivation behavior and effectiveness of NTP [116]. To lessen toxicity and fungal contamination, this technique can be used as a substitute for the thermal process [119]. NTP may be able to reduce the number of bacteria on surfaces, but longer treatment times are required [122].

Recently, it is reported that NTP technology has the potential to combat COVID-19 [28,143]. As NTP is produced with less energy and has an electron at a temperature much higher than bulk gas molecules, it can inactivate airborne viruses [251]. When using NBP for virus inactivation, it is essential to set the correct parameters and choose treatment times that allow particles to interact with the contaminated material. We believe that one of the areas of viral inactivation where plasma may be a more significant advancement is water decontamination. NTP may render troublesome enteric viruses and hardy plant viruses inactive for use in humans and/or for agricultural purposes. In any case, it is important to first evaluate any potential genotoxic and cytotoxic effects of plasma-activated water on people and plants. As several other researchers have discovered, NTP significantly increases the amount of protein oxidation that takes place in the viral capsid or coat. By producing ROS, NTP treatment puts bacteriophages into a dormant state. NTP operating parameters may favor viral DNA damage or protein inactivation, but further research is needed to confirm this. Almost every study on NTP inactivation of viruses is distinct from the others because they either deal with the treatment of various liquid volumes, various viruses, or a particular plasma source with unique properties. It is challenging to directly compare these studies and define any common inactivation parameters or mechanism of action conclusions as a result of their excessive diversity. NTP technology for viruses is still in its infancy, so more research is needed. In order to better understand which plasma particles are crucial and how they affect viruses, more precise methods are clearly needed.

Among the best techniques for removing harmful chemicals from the environment is NTP. The yield of NTP-based technology is affected by a variety of operational factors. Catalysts can, from a physical standpoint, serve as a medium for enhancing the discharge intensity or lengthening the time that reactants are retained in the plasma zone [252,253]. When a catalyst is properly added to the NTP reactor, process performance is greatly improved compared to NTP alone. As a result, several scientists have investigated using NTP in combination with catalysts to remove numerous types of environmental pollutants. With a focus on different types of environmental pollutants removal in NTP alone and a plasma-catalytic system, this review might be useful to give a description of the significant advancements in the application of the plasma-catalytic system for environmental pollutants removal mainly in the past several years. Due to its particular synergistic effect, plasma catalysis is recommended for the effective removal of environmental contaminants. Based on the characteristics of the target pollutant and the reaction conditions, it is better to select an appropriate catalyst and plasma-catalysis system configuration. Particularly, plasma-catalytic systems have effectively created and used transition metal oxide-based catalysts with increased activity. The main factors affecting the performance of plasma-catalytic systems are catalyst synthesis parameters (such as the calcination temperature, aging duration, precursor type, and supports) and operating parameters [166]. In the plasma-catalytic system, the surface characteristics of the catalyst are crucial for catalytic activity. Although significant efforts have been made to investigate the activation and characterization of catalysts in plasma, advancing our knowledge of the synergetic mechanism of plasma and catalysts, there are still many significant obstacles that must be overcome through future research. There are limitations to the advancements in the formation of plasma-catalytic systems that are closer to practical industrial applications, demanding additional research in the future.