Recent Advances in Prion Inactivation by Plasma Sterilizer

Abstract

Prions, which cause transmissible spongiform encephalopathies (TSEs), are a notorious group of infectious agents with possibly the highest resistance to complete inactivation. Although various gas plasma instruments have been developed, studies on prion inactivation using gas plasma instruments are limited. Among them, the hydrogen peroxide gas plasma instrument, STERRAD^® (Advanced Sterilization Products; ASP, Johnson & Johnson, Irvine, CA, USA), is recommended for prion inactivation of heat-sensitive medical devices. However, STERRAD^® is not a plasma sterilizer but a hydrogen peroxide gas sterilizer. In STERRAD^®, plasma generated by radio frequency (RF) discharge removes excess hydrogen peroxide gas and does not contribute to sterilization. This is also supported by evidence that the instrument was not affected by the presence or absence of RF gas plasma. However, recent studies have shown that other gas plasma instruments derived from air, nitrogen, oxygen, Ar, and a mixture of gases using corona, dielectric barrier, microwave, and pulse discharges can inactivate scrapie prions. As inactivation studies on prions other than scrapie are limited, further accumulation of evidence on the effectiveness of gas plasma using human-derived prion samples is warranted for practical purposes.

Keywords: corona plasma; dielectric barrier discharge; gas plasma; hydrogen peroxide gas plasma; prion; radiofrequency.

Figure 1

Prions exhibit the highest level of resistance to disinfection/sterilization. Bacterial spores, protozoal oocysts, and helminth eggs are highly resistant but display lower resistance than prions. Mycobacteria, small non-enveloped viruses, and fungal spores are moderately resistant. Vegetative bacteria, protozoa, fungi, algae, and large non-enveloped viruses are less resistant. Enveloped viruses are more susceptible. Illustrated based on the information sourced from the literature [1].

Figure 2

PrP^Sc accumulation is the cause of prion diseases. During prion infection, PrP^Sc is converted from PrP^C. PrP^Sc accumulates in the brain, resulting in neuronal cell loss and, finally, death. PrP^Sc: abnormal isoform of prion protein; PrP^C: cellular isoform of prion protein.

Figure 3

Plasma is the fourth state of matter. When energy is added to a solid, the state changes to liquid. Further energy addition transforms the liquid into a gas. When additional energy is applied to gaseous matter, the state transforms further into an ionized gas known as “plasma” or “gas plasma” (red).

Figure 4

Schematic presentation of RENO-S130, a hydrogen peroxide gas plasma instrument used for prion inactivation experiments. Treatment modes include non-lumen mode (28 min) or Eco mode (45 min). In both treatment modes, hydrogen peroxide gas derived from 50% hydrogen peroxide was used. Air was injected at a flow rate of 5–10 L/min, as shown. There are two plasma regions, including the dielectric barrier discharge (DBD) plasma region and the corona plasma region. Electrode 1 (stainless steel chamber wall) and electrode 2 (stainless steel covered with ceramic) are located in the DBD plasma region. The DBD plasma region is located prior to the sterilization chamber box. In the corona plasma region, residual hydrogen peroxides are degraded and removed. H₂O₂: hydrogen peroxide. Reproduced from [65], published under an open access Creative Commons CC BY 4.0 license.

Figure 5

Schematic presentation of bipolar and low-pressure plasma–triple-effect sterilization (BLP-TES) instrument. BLP-TES is a nitrogen gas plasma instrument used for prion inactivation experiments. This instrument has 15 grounding electrodes located centrally between the two upper and two lower high-voltage electrodes (four high-voltage electrodes in total). Chamber box pressure is controlled by a pressure gauge and maintained at 0.5 atmospheres during the electrical discharge at 1.5 kilo pulse per second (kpps) and the discharge current of 5–8 A as well as the discharge voltage of 15–18 kV. The temperature of the chamber box was 85 °C at 30 min, while the UV intensity was 50 mJ/cm² [49]. Reproduced from [27], published under an open access Creative Commons CC BY 4.0 license.