Plasma injection system: Reaching beyond the surface in plasma medicine applications

Lead Research Organisation: Loughborough University
Department Name: Electronic, Electrical & Systems Enginee

Abstract

Plasma, the fourth state of matter, provides a unique means for creating reactive environments at low gas temperature useful for many scientific and technological applications. For example more than half the steps required to fabricate a modern chip require plasma. Other well established multi-million applications include the lighting and the flat panel display industries. While most established technologies utilize low pressure plasmas, in recent years there has been a growing interest on developing plasmas that can be operated at atmospheric pressure and yet remain at low temperature. In particular, low temperature atmospheric pressure plasmas have made possible the treatment of biological materials that are temperature sensitive and cannot be put in vacuum environments, given birth to a fast growing scientific discipline referred to as Plasma medicine . Plasma medicine studies the interaction of gas plasmas and living cells and is being considered for a wide range of biomedical applications including sterilization of medical equipment, wound disinfection, wound healing, cancer treatment, oral/dental care, and food safety. As in any emerging technology, initial efforts have been focused in demonstrating the potential of plasmas to either kill, modify or stimulate living cells. This has been largely done in in-vitro studies where often monolayers of targeted cells are treated by plasma. Having been demonstrated the capability of plasma to modify biomolecules and the interact with potential therapeutic value with living cells, it is now time for the field to address other fundamental questions. Arguably the main two issues that plasma medicine needs to address before plasmas become widely accepted by the biomedical community are (1) selectivity, in other words, can plasma damage malignant cells while sparing healthy ones; and (2) penetration, can plasma reach underneath the surface to infer its therapeutic value. In this feasibility study we focus on the latter issue: penetration. Given the non-equilibrium character of the chemistry developed in plasmas, their action is typically limited to the surface. While this is ideal for surface modification applications where we want to preserve the properties of the bulk material, most envisaged biomedical applications require plasma treatments to reach beyond the first monolayer of cells. Although plasma treatment penetration has not been studied in detail in the past, the literature has indirect evidence that suggest that plasma treatments weaken in tens of microns. For example, the bactericidal properties of plasmas rapidly decay if cells are embedded in a biofilm or even simply stacked one on another. Addressing this potential technology killer, the proposed work undertakes the development of a plasma injection system where a combination of a plasma jet and a needle-free liquid injector are operated synergistically to enable the penetration of plasmas species inside a biological target. Taking a heuristic approach aimed at demonstrating the feasibility of the plasma injection system, we will examine the bactericidal properties of a He/O2/water plasma injection system against bacteria protected by gels acting as biological barriers. The project will include an initial characterization of the system although detailed analysis aimed at unravelling the underlying physico-chemical processes are envisaged in follow-up studies.

Planned Impact

Given the incipient state of the field of plasma medicine, the direct beneficiaries of this work are academics working on this field. This has been discussed in a previous section, but in sort, the proposed project pushes the current frontiers of plasma medicine beyond current capabilities by enabling the treatment of not just superficial cells but also cells inside tissue. Any breakthrough in this line will create new opportunities for plasma and will be welcome by the community. Having been received with disbelieved by non-plasma disciplines at the beginning, plasma is emerging as a new technology with potential revolutionary solutions to some traditional bio-medical problems. For example, plasma is a powerful bactericide capable of inactivating antibiotic-resistant microorganisms such as MRSA, prions and potentially the recently discovered NDM-1 'superbug'. Therefore, given the interdisciplinary nature of plasma medicine, results of the project are also likely to excite scientist working on non-plasma disciplines (e.g. microbiology, immunology) who might have looked at plasma technology reluctantly in the past due to its lack of penetration. To them plasma could offer a new out-of-the-box solution to some of their scientific problems. Given the incipient state of the field, the current industrial sector is very limited. Nonetheless, as plasma approaches its full potential it will create business opportunities and attract increasing commercial interest. The development of an enabling technology as the one proposed in this project will generate new IP and create business opportunities that will benefit the UK economy. With potential revolutionary solutions to problems regarding sterilization of medical instruments, skin disinfection, inactivation of antibiotic-resistant bacteria, wound healing, food safety, oral/dental care, and cancer, any advance in the field of plasma medicine has the potential to impact on the health care and food industry sectors. It would not be surprising neither that successful stories on any of the above mentioned applications will influence government policy making for example with regard to sterilization policies. In the end, any new solution in the health and food safety sectors will enhance the quality of life of every citizen.

Publications

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Bruggeman P (2017) Foundations of atmospheric pressure non-equilibrium plasmas in Plasma Sources Science and Technology

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Castello Beltran C (2014) Comparative Study of Chemical Probes for Ozone Detection in Lorentz Workshop: Gas/Plasma-Liquid Interface: Transport, Chemistry and Fundamental Data

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Castello Beltran C (2013) Fluorescence Probe for Determining the Ozone Dose Delivered by Plasmas in The 11th UK Technological Plasma Workshop

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Castelló Beltrán C (2015) Virtues and limitations of Pittsburgh green for ozone detection. in Chemical communications (Cambridge, England)

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Dolezalova E (2014) Study of Plasma-induced Inactivation of a Reference Micro-organism in International Symposium on High Pressure Low Temperature Plasma Chemistry (HAKONE XIV)

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Iza F (2013) Water in low-temperature atmospheric-pressure plasmas in International Conference on Plasma Science and Applications - ICPSA2013

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Iza F (2014) Water in atmospheric-pressure helium rf plasmas in The 9th EU-Japan Joint Symposium on Plasma Processing (JSPP2014)

 
Description Fast moving small droplets can be used to perforate skin tissue models. When these droplets transit through a plasma discharge, conditions can be engineered for the droplet to entrap reactive species without evaporating, subsequently delivering these reactive species into the skin tissue model.
Exploitation Route The results suggest that a multi-droplet system would be required to deliver a high enough dose of reactive species.

The system can be used in other applications that require transfer of species from the plasma to the liquid phase.
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description IPP - Czech Rep 
Organisation Academy of Sciences of the Czech Republic
Department Institute of Plasma Physics
Country Czech Republic 
Sector Public 
PI Contribution Biological expertise and lab facilities
Collaborator Contribution Man power - Plasma system characterization
Impact Conference papers
Start Year 2013
 
Description Liverpool 
Organisation Tsinghua University China
Country China 
Sector Academic/University 
PI Contribution Computational modelling
Collaborator Contribution Pulse power expertise
Impact Conference papers Journal publications
Start Year 2011
 
Description Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Computational modelling
Collaborator Contribution Pulse power expertise
Impact Conference papers Journal publications
Start Year 2011
 
Description Peter 
Organisation University of Minnesota
Country United States 
Sector Academic/University 
PI Contribution Computational modelling
Collaborator Contribution Experimental OH, H2O2 measurements
Impact Journal Publication
Start Year 2013
 
Description Xi'an Jiatong 
Organisation Xi'an Jiaotong University
Country China 
Sector Academic/University 
PI Contribution Computational expertise, computational models
Collaborator Contribution Data Mining, man power
Impact Conference papers Journal publications
Start Year 2011