Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or "cold" plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5 log 10 kill in 30 s by damaging the cell surface in a time-dependent manner, resulting in a loss of membrane integrity, leakage of intracellular components (nucleic acid, protein, ATP), and ultimately focal dissolution of the cell surface with longer exposure time. This occurred with similar kinetic rates among methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. We observed no correlative evidence that plasma induced widespread genomic damage or oxidative protein modification prior to the onset of membrane damage. Consistent with the notion that plasma is superficial, plasma-mediated sterilization was dramatically reduced when microbial cells were enveloped in aqueous buffer prior to treatment. These results support the use of nonthermal plasmas for disinfecting multidrug-resistant microbes in environmental settings and substantiate ongoing clinical applications for plasma devices. P lasmas are ionized gases that exhibit a plethora of applied temperature and physical properties. In biomedical applications, plasmas are supported by an electric field such that electrons receive external energy more rapidly than surrounding ions (5). Plasmas generate thermal energy (heat) when heavy particle temperatures equilibrate with electron temperature but are considered "nonthermal" when the cooling of ions and uncharged molecules is more effective than the energy transfer from electrons to gas (5). Nonthermal or "cold" plasmas produce a variety of shortlived and long-lived reactive components, including charged particles and UV radiation, without significantly raising temperature (25). Nonthermal plasmas (NTPs) are applied extensively in materials science to modify the properties of carbon-based materials but have also shown promise for applications in biology and med-

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This Perspective reviews the fundamental physics of space–charge interactions that are important in various media: vacuum gap, air gap, liquids, and solids including quantum materials. It outlines the critical and recent developments since a previous review paper on diode physics [Zhang et al. Appl. Phys. Rev. 4, 011304 (2017)] with particular emphasis on various theoretical aspects of the space–charge limited current (SCLC) model: physics at the nano-scale, time-dependent, and transient behaviors; higher-dimensional models; and transitions between electron emission mechanisms and material properties. While many studies focus on steady-state SCLC, the increasing importance of fast-rise time electric pulses, high frequency microwave and terahertz sources, and ultrafast lasers has motivated theoretical investigations in time-dependent SCLC. We particularly focus on recent studies in discrete particle effects, temporal phenomena, time-dependent photoemission to SCLC, and AC beam loading. Due to the reduction in the physical size and complicated geometries, we report recent studies in multi-dimensional SCLC, including finite particle effects, protrusive SCLC, novel techniques for exotic geometries, and fractional models. Due to the importance of using SCLC models in determining the mobility of organic materials, this paper shows the transition of the SCLC model between classical bulk solids and recent two-dimensional (2D) Dirac materials. Next, we describe some selected applications of SCLC in nanodiodes, including nanoscale vacuum-channel transistors, microplasma transistors, thermionic energy converters, and multipactor. Finally, we conclude by highlighting future directions in theoretical modeling and applications of SCLC.

While well established for larger gaps, Paschen's law (PL) fails to accurately predict breakdown for microscale gaps, where field emission becomes important. This deviation from PL is characterized by the absence of a minimum breakdown voltage as a function of the product of pressure and gap distance, which has been demonstrated analytically for microscale and smaller gaps with no secondary emission at atmospheric pressure [A. M. Loveless and A. L. Garner, IEEE Trans. Plasma Sci. 45, 574-583 (2017)]. We extend these previous results by deriving analytic expressions that incorporate the nonzero secondary emission coefficient, c SE , that are valid for gap distances larger than those at which quantum effects become important ($100 nm) while remaining below those at which streamers arise. We demonstrate the validity of this model by benchmarking to particle-in-cell simulations with c SE ¼ 0 and comparing numerical results to an experiment with argon, while additionally predicting a minimum voltage that was masked by fixing the gap pressure in previous analyses. Incorporating c SE demonstrates the smooth transition from field emission dominated breakdown to the classical PL once the combination of electric field, pressure, and gap distance satisfies the conventional criterion for the Townsend avalanche; however, such a condition generally requires supra-atmospheric pressures for breakdown at the microscale. Therefore, this study provides a single universal breakdown theory for any gas at any pressure dominated by field emission or Townsend avalanche to guide engineers in avoiding breakdown when designing microscale and larger devices, or inducing breakdown for generating microplasmas.