An emerging field of plasma medicine is discussed, where non-equilibrium plasmas are shown to be able to initiate, promote, control, and catalyze various complex behaviors and responses in biological systems. More importantly, it will be shown that plasma can be tuned to achieve the desired medical effect, especially in medical sterilization and treatment of different kind of skin diseases. Wound healing and tissue regeneration can be achieved following various types of plasma treatment in a multitude of wound pathologies. Non-equilibrium plasmas will be shown to be non-destructive to tissue, safe, and effective in inactivation of various parasites and foreign organisms.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ppap.200700154

Applied Plasma Medicine

Plasmas for medicine

Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. However, the authors are attempting to make first steps in this direction. In this paper, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered.

https://iopscience.iop.org/article/10.1088/1367-2630/11/11/115020/pdf

Physical and biological mechanisms of direct plasma interaction with living tissue

Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.

/pdf/cold-plasma-selectivity-and-the-possibility-of-a-paradigm-3m4vrgmkdc.pdf

Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy

https://biblio.ugent.be/publication/792032/file/8599453.pdf

Nonthermal Plasma Technology as a Versatile Strategy for Polymeric Biomaterials Surface Modification: A Review

In this paper we describe the hitherto unravelled facts on the interactions of a cold atmospheric plasma with living cells and tissues. A specially designed source, plasma needle, is a low-power discharge, which operates under the threshold of tissue damage. When applied properly, the needle does not cause fatal cell injury which would result in cell death (necrosis). Instead, it allows precise and localized cell removal by means of the so-called cell detachment. In addition, plasma can be used for bacterial disinfection. Because of mild treatment conditions, plasma disinfection can be performed in vivo, e.g. on wounds and dental cavities. Presently, one strives to obtain a better control of the operating device. Therefore, plasma has been characterized using a variety of diagnostics, and a smart system has been designed for the positioning of the device with respect to the treated surface.

https://iopscience.iop.org/article/10.1088/0963-0252/15/4/S03/pdf

Plasma needle for in vivo medical treatment: recent developments and perspectives

In the study of plasma–surface interactions, a well-defined distance from the surface is desired. In this paper, an innovative method is proposed for using the intrinsic properties of a low-power atmospheric plasma to control this distance. It is proposed that the vicinity of a (even poorly) conducting surface imposes a change in the plasma impedance. This effects the reflection of electrical power, which can easily be measured, and provides a non-contact sensor for the distance between the plasma source and the substrate. For this sensor to work, a low-loss and efficient matching network is designed, such that changes in the reflected power are relatively high. With this high-quality matching network at hand, a characterization of the plasma needle is performed in terms of impedance and related parameters. Although characterization is not essential for the development of the sensor, it contributes to fundamental knowledge about the plasma source. Finally, coherence measurements are performed to determine the performance of the above described sensor in different experimental settings.

http://www.mate.tue.nl/mate/pdfs/6805.pdf

Development of a smart positioning sensor for the plasma needle

Summary form only given. In pursuit of minimum-invasive surgery one has to develop techniques, that allow specific cell removal or rearrangement without influencing the whole tissue. In conventional or laser surgery individual cells undergo accidental cell death (necrosis), which is followed by inflammation and may lead to permanent tissue damage. In contrast, cold plasma techniques allow cell removal without necrosis. At the Eindhoven University a suitable small-size plasma source has been developed (plasma needle) and several potentially beneficial plasma-cell interactions have been identified. These reactions include: cell detachment without affecting cell viability, induction of apoptosis (programmed cell death), and altering cell proliferation rate. So far the tests have been performed on cells in culture (mouse fibroblasts or human epithelial cells of lung carcinoma), but recently we have introduced a new model: tissue engineered skin. The effect of plasma-induced cell detachment has been already identified in this model. At present we check for early markers of tissue damage and differentiation of keratinocytes after plasma treatment. In parallel, we continue the study on mouse fibroblasts. MTT assay for long-term viability has been performed. Cell proliferation rate has been monitored using the BrdU assay (a marker for newly formed DNA). A strong link between the plasma properties and triggered cell reactions is expected. Moderate cell damage, which leads to (reversible) detachment or apoptosis, may result from interactions with plasma-produced radicals. The ROS (reactive oxygen species) are known to play an important role in these processes. We have shown that plasma radicals can exist in the liquid phase (cell culture medium). Micro-molar concentrations of ROS from the plasma have been detected using a fluorescent probe in combination with (confocal) LIF, and correlated with gas-phase plasma properties. We conclude that ROS concentrations are within the safe range: the radicals can trigger specific cell reactions, but are unable to kill the cells.

Plasma interactions with living cells

This paper presents a novel control strategy for real-time controlled restraint systems. Todaypsilas restraint systems typically include a number of airbags, and a three-point seat belt with load limiter and pretensioner. In the class of realtime controlled restraint systems, the restraint actuator settings are continuously manipulated during the crash. The control strategy developed here is based on reference management, in which a nonlinear device - a reference governor - is added to a primal closed loop controlled system. This governor determines an optimal setpoint in terms of injury reduction and constraint satisfaction by solving a constrained optimization problem. Prediction of the vehicle motion, required to predict future constraint violation, is included in the design and is based on linear regression of past crash data. Simulation results with a MADYMO model show that a significant injury reduction is possible, without prior knowledge of the crash. Furthermore, it is shown that the algorithms are sufficiently fast to be implemented on-line.

/pdf/reference-governors-for-controlled-belt-restraint-systems-4nsg0ez18h.pdf

Reference governors for controlled belt restraint systems

In this paper, a method is presented to estimate the motion of a vehicle occupant in frontal impact. Knowledge of the occupant's motion during a crash can significantly reduce the risk of injury, as restraint systems could be real-time adapted to the optimal settings. It is shown that the chest acceleration of the occupant, an important measure of injury, is accurately estimated by filtering of the belt displacement at the retractor side. Low order, nonlinear models are constructed from complex models, and a state estimator filter is designed using a linearization of these low order models.

/pdf/state-estimator-design-for-real-time-controlled-restraint-1u3wll18mh.pdf

E.P. van der Laan

Papers

Plasma needle for in vivo medical treatment: recent developments and perspectives

Development of a smart positioning sensor for the plasma needle

Plasma interactions with living cells

Reference governors for controlled belt restraint systems

State Estimator Design for Real-time Controlled Restraint Systems