Microplasma-assisted manipulation of intact airborne bacteria for real-time autonomous detection

Lead Research Organisation: University of Ulster
Department Name: Nanotechnology and Adv Materials Inst

Abstract

In this project we are proposing a new method of directly detecting airborne bacteria. In many fields, the dangers of infection by pathogens, for example anthrax, need to be faced and there are major challenges with existing techniques in quickly assessing the danger so that rapid public safety responses are possible . Current techniques may be slow, expensive or need trained people and specialised laboratories. We want to devise a detection technique based on accurate measurement of a number of physical characteristics of bacteria that will allow differentiation of even similar strains so that the true pathogens can be clearly identified. This is a difficult challenge and further, we aim to show in our proof of principle, that it will be possible to design a detector that is low cost, reasonably portable and can work autonomously i.e. without continuous human intervention. Success would then encourage the development and deployment of this remote monitoring technology in critical public spaces, for example large public events and hospitals.

Planned Impact

The proposed research will investigate a new method of detecting and identifying intact pathogenic bacteria which avoids the limitations of current culture, biosensor or spectrometric approaches and, if successful, would be compact, autonomous, rapid and relatively low cost. Significant ground-breaking impact can be expected in arenas that would directly affect human health and welfare, such as, terrorism and bio-security, airborne hospital-acquired infections, public building and food safety. It may also have an impact in the development of light-weight detectors for space missions in the search for extra-terrestrial life. New instrumental techniques will help explore the physics of biological processes, currently a Grand Challenge in the physical sciences, offer new avenues of research in the Physics of Life and help engender new research collaborations between physics and biology.
Terrorism & security: the ongoing threat of pathogenic agent dispersal, whether chemical, nuclear or biological (CBRN), has exercised governments worldwide since the Anthrax attacks of 9/11. Rapid advances in biotechnologies are creating new vulnerabilities and new forms of biological warfare and such an attack is considered a Tier One priority risk in the UK's National Security Strategy (2010). Robust management of such a threat as well as public assurance would benefit considerably from advanced early-warning technology at critical locations, (e.g. London Underground, international airports, Olympics) and ultimately as part of a national network of environmental monitoring stations in urban centres. The proposed detection principle will allow flexible and remote reconfiguration of the sensor focus during and immediately after an attack or accidental release, as local field data is collected from other sources and analysed. Our proposed technology will be compact and hence also suitable for portable/ transportable deployment in the aftermath of a suspected event.
Hospitals, Health Laboratories & Public Buildings: Advances in medical therapies (e.g. chemotherapy) have led to greater numbers of immunocompromised patients who are highly susceptible to dangerous hospital-acquired opportunistic infections. A viable detection technology for pathogenic bacteria with selective or portable deployment could have a major impact in a hospital environment, as a method of limiting airborne infection risks. Relevant pathogens include: (i) aerobic fungi dispersed by poorly functioning ventilation; (ii) bacterial pathogens (e.g. M. tuberculosis, S. aureus) which can persist in the environment for long periods; (iii) waterborne species (e.g. Legionella spp.) spread by exposure to contaminated aerosols. Providing an airborne monitoring capability with real time response for priority target species, would be highly beneficial, especially for protective patient care environments, operating theatres, isolation wards etc. A similar approach would be suitable for public buildings (e.g. Legionnaire's disease) and in the food industry where airborne dispersal is a source of contamination that could result in serious food poisoning. The development of a mobile real-time detector would allow the source of any airborne outbreak to be traced quickly.
Extra - Terrestrial Life: Detecting microorganisms elsewhere in the universe invokes considerable scientific and public interest. During the coming decades, the search for life on Mars will be a central focus of both NASA and the European Space Agency (ESA) missions while Europa, Jupiter's moon, has provoked considerable interest as a possible location for extraterrestrial biology. The prospect of simple, direct and unambiguous differentiation between biological microorganisms and non-biological particles in-situ would be very appealing. The proposed bacteria detector could have immediate and significant impact for planned planet and comet probe missions through greatly reduced weight and operational complexity
 
Description Our primary aim was to explore experimental techniques for directly measuring the properties of individual intact airborne bacteria. These would necessarily be physical properties measurements and our hypothesis is that from a number of simultaneous measurements we would be able to gain important information such as the presence of bacteria and also identify the particular species & strain. We have made significant advances towards this goal and these will be reported fully in the near future. Firstly we have developed a coaxial flow microfluidic chamber where micron-sized aerosol droplets can be transported through a high intensity steady-state non-equilibrium plasma. This has been verified by detailed electrical and optical imaging measurements. We have been able to dress these droplets with a large amount of electrical charge. This is important as it will enable us to steer and trap these droplets. We have measured the values of charge on the droplets under various conditions and, despite 40 years of theoretical predictions, we believe these to be the first such measurements and results will soon be available publicly along with simulations. Next we have transported individual intact bacteria wrapped in a water droplet through the plasma chamber. Through the plasma interactions and charging processes both transient chemical and biological effects have been initiated in bacteria loaded droplets. We have explored techniques to investigate such effects with the challenge of very small volumes and numbers of bacteria. Under controlled conditions we can ensure that plasma-exposed bacteria remain intact and viable and have characterised their damage and response. This has clearly demonstrated little physical, structural or morphological change in bacteria which is important for ultimate detection. Separately, we have managed to trap water droplets and watch them evaporate. The next step is to allow the charged water droplet containing the bacteria to evaporate. If we can keep the droplet away from unstable modes, and simulations suggest this is possible, the charge (maybe >10,000 electrons as indicated by simulations) will transfer to the individual bacteria. With such an extremely high charge to mass ratio, trapping and manipulating isolated bacteria for identification purposes could become a reality in the near future.

A number of new research directions and questions have opened up and new results have been published. For example the effects of extremely fast mixing and chemical reactions in ultra-small volumes have been observed - an important research and technological challenge in microfluidics and nanomaterials synthesis for applications from catalysis to biomedical imaging/theranostics. We have oberved important chemical reactions that occur many orders of magnitude faster than in standard chemistry.

Understanding the interactions between electrons and water is very important in a range of fields from radiation studies to atmospheric chemistry. The experimental techniques established here provide an ideal laboratory for such studies with electron energies much lower than otherwise possible. The new fields of plasma medicine and plasma agriculture involve plasma interactions with e.g. living tissue, tumour cells, microbial infection and/or delicate plants. This research has provided a tentative yet exciting prospect of removing the plasma to a much more remote location but transmit its effect through droplets, without loss of efficacy, and therefore improve the technological feasibility of plasma medicine/agriculture. With respect to bacteria in particular, the current findings and the experimental techniques offer a unique opportunity to study and realise new non-antibiotic approaches to the global challenge of Anti-Microbial Resistance (AMR). We have observed the direct effects of reactive oxygen radicals, supplied by the plasma, on individual living cells and DNA. We also potentially observed previously unsuspected interactions between very low energy electrons, water and biological species. Chemical simulations are underway to help confirm certain hypotheses and publication is expected soon. This could have an important impact on our understanding of radiolysis and living matter.
Exploitation Route We envisage the research continuing along the original pathway towards the detection of pathogens by physical means but, with the valuable experience and results gained, the major hurdles ahead can be more clearly specified and hence the future research programme elaborated with greater detail. We expect that the beneficiaries originally highlighted in the Pathways to Impact (e.g. Public Safety from Bio-Attack to airborne infection in hospitals) remain valid. We also expect that the new techniques established for charging and manipulating individual bacteria will be beneficial for the study of the physical properties of bacteria which could become an important factor in exploring new anti-microbial resistance approaches. In addition, the new research directions uncovered will likely have significant uptake initially in applied academic fields related to nanomaterials chemistry, catalysis, radiation chemistry, plasma medicine and agriculture. These research areas could progress relatively rapidly to impact beyond the academic sphere.
Sectors Agriculture, Food and Drink,Chemicals,Electronics,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Security and Diplomacy

 
Description Academic outcomes, as reported in key findings, have been used to initiate first steps to commercialisation. A patent has been filed (January 2017), discussions with Innovation advisory group, and university Innovation Office have been initiated to draw up a business plan. Patent Application has progressed to the next stage.
First Year Of Impact 2016
Sector Chemicals,Healthcare
Impact Types Economic

 
Description IOP Ireland committee membership
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
 
Description IOP UK Plasma Physics Committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Grant for Research & Development
Amount £3,681,278 (GBP)
Funding ID RD0714186 
Organisation Invest Northern Ireland 
Sector Public
Country United Kingdom
Start 11/2015 
End 10/2020
 
Description PhD Studentship 2013 - 2016
Amount £65,000 (GBP)
Organisation Government of Northern Ireland 
Department Department for Employment and Learning Northern Ireland (DELNI)
Sector Public
Country United Kingdom
Start 10/2013 
End 09/2016
 
Description PhD Studentship 2014 - 2017
Amount £65,000 (GBP)
Organisation Government of Northern Ireland 
Department Department for Employment and Learning Northern Ireland (DELNI)
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description Research Challenge Fund (Ulster)
Amount £29,969 (GBP)
Organisation Ulster University 
Sector Academic/University
Country United Kingdom
Start 11/2014 
End 07/2015
 
Description Science for Peace and Security (SPS) Programme
Amount € 180,000 (EUR)
Funding ID EAP.SFPP 984555 
Organisation North Atlantic Treaty Organization (NATO) 
Sector Public
Country Belgium
Start 06/2014 
End 06/2016
 
Title Plasma-aerosol microreaction 
Description Developed a new method for microreaction through aerosol plasmas. 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact A patent is being filed. 
 
Description Brunel-Harjit 
Organisation Brunel University London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have produced expertise and time/resources to produce a publication.
Collaborator Contribution The collaborators contributed with their expertise and time to produce new results for a publications.
Impact Rose BAJ, Singh H, Verma N, Tassou S, Suresh S, Anantharaman N, Mariotti D, Maguire P "Investigations into nanofluids as direct solar radiation collectors" Solar Energy 147 (2017) 426
Start Year 2016
 
Description COST Action TD1208 
Organisation University of Bologna
Country Italy 
Sector Academic/University 
PI Contribution Within the COST-Action TD1208 we participated to workshop and lead one of the Workgroup. We have also hosted 3 researchers from partners in the network.
Collaborator Contribution Students/researchers from the network visited us to carry out experiments and also continued with other experiments in their own institution.
Impact Bruggeman P J, Mariotti D et al. "Plasma-liquid interactions: a review and roadmap" Plasma Sources Science and Technology 25 (2016) 053002 - Invited Topical Roadmap; Tarasenka N, Butsen A, Pankov V, Velusamy T, Mariotti D, Tarasenko N "Laser assisted preparation of doped ZnO nanocrystals" Nano-Structures & Nano-Objects 12 (2017) 210; Velusamy T, Liguori A, Macias-Montero M, Padmanaban DB, Carolan D, Gherardi M, Colombo V, Maguire P, Švrcek V, Mariotti D "Ultra-small CuO nanoparticles with tailored energy-band diagram synthesized by a hybrid plasma-liquid process" Plasma Processes & Polymers 14 (2017) 1600224; Tarasenka N, Stupak A, Tarasenko N, Chakrabarti S, Mariotti D "Structure and optical properties of carbon nanoparticles generated by laser treatment of graphite in liquid" ChemPhysChem 18 (2017) 1074
Start Year 2013
 
Description Sankaran Lab USA 
Organisation Case Western Reserve University
Country United States 
Sector Academic/University 
PI Contribution Joint research into droplet transport through low temperature plasmas for biomedical and materials applications. We share equipment and specialised expertise on the in-situ measurement of plasma impedance, along with modelling for joint publication.
Collaborator Contribution We share equipment and specialised expertise on the in-situ measurement of plasma impedance, along with modelling for joint publication. We use complementary configurations and diagnostics instrumentation, with impedance measurement using shared instrument as benchmark
Impact Initial data for analysis
Start Year 2018
 
Description 20th International School Master Class on Low-Temperature Plasma Physics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presentation (60 min + 15) to postgraduate students at the annual international Low Temperature Plasma Physics School in Bad Honnef, Germany. The school is residential and detailed discussions with students and groups are carried out during the residential stay. The Master Class series outlines new research directions based on the techncial aspects of the curriculum.
Year(s) Of Engagement Activity 2016
URL http://www.plasma-school.org/
 
Description Anti-Microbial Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Scoping exercise to establish partnerships among academic, health professionals, data experts, veterinary and business in order to draw up a roadmap and establish collaborations for tackling Anti-Microbial Resistance
Year(s) Of Engagement Activity 2015
URL http://www.challengecluster.com/home.html
 
Description BBC TV Breakfast bulletins 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Explained the outline of the proposed research into bacterial detection to a general, non-technical audience on breakfast television.

Increased awareness in general of the latest scientific approaches to detecting bacteria and increased understanding of the importance of tackling this problem in specific situations e.g. hospitals and public spaces. Awareness raised among a number of commercial interests.
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/programmes/b01r6tpb
 
Description Beijing Sea on a Chip 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invitation to present at scoping workshop in Beijing on future technology for climate change sensing in oceans
Year(s) Of Engagement Activity 2015
 
Description Biosensors for Security Workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This talk brought new ideas and potential techniques from a Physics/Engineering perspective to a Bio-related expert audience working in Government and in commercial enterprises. The aim was to promote the potential for physical measurement techniques as a complement or substitute for existing microbiological techniques in rapid airborne pathogen detection.

Inspired consideration of radical new approaches to a currently intractable challenge of considerable societal significance, among experts and decision makers
Year(s) Of Engagement Activity 2013
URL http://us1.campaign-archive1.com/?u=194e1879e296124900f619838&id=fe1fb95d16&e=c719894b98
 
Description Cambridge Particle Meeting 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk given to academics and industrialists in the field of aerosols and environmental measurement science and technology
Year(s) Of Engagement Activity 2015
URL http://www.cambridgeparticlemeeting.org
 
Description LoC Workshops ESCAMPIG 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Local Organising Committee of E?urophysics Conference on the Atomic and Molecular Physics of Ionized Gases, 2018 - participated in organisation of two interdisciplinary interactive workshops: (i) Plasmas and Living Systems and (ii) Plasmas in Multiphase Media
Year(s) Of Engagement Activity 2018
URL https://www.gla.ac.uk/schools/physics/research/groups/astro2/escampig/
 
Description Ocean Sensors Overview and Collaboration, Beijing July 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientific discussion between ocean and water environmental scientists from Chinese government research institutes and invited international experts to discuss future roadmap and collaboration for ocean and inland water pollution and technologies for monitoring and remediation. Held in University of Peking, Beijing, July 2016.
Year(s) Of Engagement Activity 2016