Wireless communication with cells towards bioelectronic treatments of the future

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Electroceutics, or bioelectronic drugs are defined as treating disease via control of the body's electrical signals and are the future therapeutic intervention. Examples of electroceutic devices include the cochlear implant, retinal implants forming a bionic eye, pace maker for modulating heart rhythm, deep brain stimulators for treating Parkinson's and other neurological disorders, and most recently a wraparound vagus nerve stimulator to treat arthritis. They rely on electrical stimulation of neuronal pathways that cause a functional effect to treat a disease or an ailment. Bioelectronic based therapies typically involve the merging of electronic devices with neuronal cells/tissues. This generally involves initial invasive surgery for implantation of the electronic component which also needs regular replacement. The electronic components of the device stimulates nerves cells/tissues in an unprecise manner. However, whilst treating disease by modulating neural relays has been the focus of research, almost no studies exist describing bioelectronic based therapies for non-neuronal cells. This is surprising considering all cells are electrically active. The field of electroceutics is an emerging strategy as an important method for disease intervention and will be increasingly important in the management of human disease. In order for electroceutical therapies to fulfil their potential there are still a number of challenges to be solved. These include

*A more thorough understanding of how cellular electrical talk malfunctions underpin disease, and a more targeted approach in modulating the cellular-electrical relays that underpin sickness.
*A broadening of electroceutical therapeutic intervention from nervous system application as well as other cell and tissue types.
*A need to avoid invasive surgery thereby making the technology more adaptable via development of wireless technology.

The research proposed will work towards addressing these challenges by developing new electrochemical based wireless technology, which may avoid invasive surgery and will be applied to treating non-neuronal based diseases such as cancer. In addition, by combining 3D printing of electrochemical systems with the wireless cellular actuation, we plan to be able to target and control specific neuronal circuits. The research exploits concepts and tools from electrochemistry, nanochemistry, supramolecular chemistry, additive manufacturing and bionanotechnology to develop electrochemical based wireless nanotechnology to sense and actuate cellular behaviour. By bringing to fruition the application of electrochemistry to electroceutics in developing such novel disruptive technology it will significantly advance healthcare technology. In addition it will make a profound and significant impact in the broad fields of biosensors applications in many areas such as biomedical diagnostics, pharmaceutical industry, defence and environmental monitoring and offer new research tools to study cellular electrochemistry.

Planned Impact

During the proposed project we will develop a wireless based electrochemical bioelectronic therapeutic. The technology will provide a completely new approach to treating cancer and potentially diseases that are underpinned by neuro dysfunction. The research outcomes will have a far reaching and diverse impact within the medical, pharmaceutical, biomedical, scientific and industrial communities. The researchers, academics and industrial partners involved will benefit through participation in an internationally leading research effort and help to define the newly emerging area of bioelectronic approaches to therapeutics. The Post-doctoral researchers and PhD student recruited through this project will have unique training to contribute and lead the blossoming industry of bioelectronics. The project will develop researcher skills in three key areas: 3D printing coupled with nano-wireless fabrication of multidimensional bio-functional systems, development of new bioelectronics and new nanotechnology. These are areas that are key for future development of new electroceutics which is a focus for growth in the UK and where there is a demonstrable need for multidisciplinary new high level skill sets. The underpinning technology will provide a platform for research into innovative bioelectronics, as well as providing researchers new tools from other disciplines because they can create new sensors and actuators for their research field. This will impact on researchers in fields of cell biology, environmentally sensing and agrochemical.

UK industry will benefit through new research that further enhances the UK's leading position in bioelectronics with GSK being the pioneers. The research will impact existing products and new product conception and realisation, with corresponding economic, societal, healthcare and environmental benefits. Pharmaceutical companies and diagnostics companies involved in the project will benefit economically. Other industries such as the electronic industrial capacity will also benefit because we will 3D print unique conductive geometries and ensure new capabilities of printing 3D electronics which are not currently possible. Additive manufacturing is currently an expanding UK industry whilst the research efforts are concurrently broadening and deepening to multi-functional / multi-material systems is approaching a cliff-edge where insufficient human capital will be available to maintain the UK lead. This project will contribute to reducing this people deficit in this field by training and developing the researchers involved in the project and the core skills that are required to develop bioelectronics and additive manufacturing technology both academically and industrially.

Society will benefit through the expedited realisation of advanced multifunctional bioelectronics devices which will have multi-sectoral benefits from improved healthcare devices and treatment options. The healthcare system will benefit through the genuine advancement in technologies which have the capability to help deliver on the need for advancements in healthcare and advanced pharmaceutical/medical devices, helping alleviate current, and the inevitable future demands on healthcare services.

The tailored support package offered by the University of Nottingham will ensure Dr Rawson leads this area to material outcome by developing new state of the art electroceutics which will impact on future healthcare technology and improve patient outcomes as the technology will be less invasive than that currently used. In the long term this will result in new non-invasive healthcare technology for cancer therapies and neuronal dysfunction. In addition the new team formed which includes Chemists, Biologists, Engineers and Clinicians ensures that the knowledge and expertise is readily adaptable to drive these new tools to market.

Publications

10 25 50
 
Title Electric Field Induced Biomimetic Transmembrane Electron Transport Using Carbon Nanotube Porins (Small 32/2021) 
Description Journal Front Cover 
Type Of Art Image 
Year Produced 2021 
Impact Incraesed vision of the work 
URL https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202170164
 
Title Pod Cast 
Description Interview with MRS 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact Enhanced audience knowledge 
URL https://www.stitcher.com/show/mrs-bulletin-materials-news-podcast/episode/episode-24-gold-nanopartic...
 
Description We have established that we can drive redox reactions via wireless electrochemistry at the nanoscale. We have developed a new technique based on this to fabricate bioelectronic interfaces in situ. We have also developed technology showing that we can modulate protein orientation on conductive nanoparticles which affect their biological activity. We have developed tools to hijack bioelectricity to drive polymerization events allowing for the merging of the biotic and Abiotic world.

We now have proof of concept that we can use wireless stimulation to kill the patient-derived cancer cells. We have also invented technology to modulate membrane electron transfer via CNTs and are developing the underlying theory of why this happens at cell-friendly voltages.
Exploitation Route N/A
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other

 
Description Increased public awareness of bioelectronic medicine. Was also involved in BBSRC strategic meeting on bioelectrical engineering which resulted in priority area in responsive mode grants
First Year Of Impact 2023
Sector Government, Democracy and Justice
Impact Types Societal

 
Description BBSRC international Partnership
Amount £20,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2022 
End 03/2023
 
Description EPSRC Early Career Equipment block grant
Amount £100,000 (GBP)
Organisation University of Nottingham 
Sector Academic/University
Country United Kingdom
Start 03/2019 
 
Description Enablement Grant
Amount £10,000 (GBP)
Funding ID E21-1135058786 
Organisation Royal Society of Chemistry 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2021 
End 08/2022
 
Description Quantum Medicine Approach to Treat Cancer
Amount £65,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2023 
End 12/2023
 
Description Prof A Now, LLNL 
Organisation Lawrence Livermore National Laboratory
Country United States 
Sector Public 
PI Contribution A postdoctoral researcher visited Alex's lab and provided biological expertise and knowhow in performing cell experiments.
Collaborator Contribution Alex provided training in how synthesis short CNT porins in cells and liposomes. This knowledge and expertise in building the rig to facilitate this has been transferred back to Nottingham.
Impact Poster Presentation: Gordon Research Conference 2019, USA Probing, Manipulating and Understanding Cell-Materials Interfaces to Achieve Electrical Continuity Poster Presentation: Asilomar Bioelectronics Symposium 2019, California, USA Oral Presentation: Elecrtochem 2019, UK
Start Year 2018
 
Description Prof Mike Mcalpine, University of Minnesota 
Organisation University of Minnesota
Country United States 
Sector Academic/University 
PI Contribution We provided know-how on forming conductive materials for 3D printing of extracellular matrix towards building 3D-bioelectronic devices.
Collaborator Contribution Mike provided intellectual input and access to specialized additive manufacture equipment. A 6-month placement by one of the Post Doctoral researchers was undertaken in Mike's lab and knowledge transfer occurred when the candidate returned to Nottingham.
Impact This is a multi-disciplinary collaboration with Minnesota providing engineering expertise combined with pharmaceutical and biological expertise from Nottingham.
Start Year 2019
 
Title Team Bot app 
Description AZURE used to create a Bot App for teaching the research group bioelectronics 
Type Of Technology Webtool/Application 
Year Produced 2021 
Impact Increased understanding and this it's ownership has been transferred to University to trial as a teaching aid. 
 
Description Asilomar Bioelectronics Symposium, Pacific Grove, CA, USA (2019) - Awarded best poster presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Combination of mechanical and electrical cues to develop novel bioelectronic micro-scaffolds, Paola Sanjuan-Alberte, Jayasheelan Vaithilingam, Chris Denning, Richard JM Hague, Morgan R Alexander, Frankie J Rawson. Asilomar Bioelectronics Symposium, Pacific Grove, CA, USA (2019) - Awarded best poster presentation
Year(s) Of Engagement Activity 2019
 
Description Electrochem talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact A talk on Tracking ultrashort carbon nanotubes in NG108 neurons was given
Year(s) Of Engagement Activity 2019
 
Description MRS interview 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview for MRS bulletin which was published as a blog/podcast
Year(s) Of Engagement Activity 2019
URL https://mrsbulletin.buzzsprout.com/244633/2310434-episode-24-gold-nanoparticles-modify-electrical-be...
 
Description Modulating Bioelectricity in cancer towards quantum theapeutics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact A talk to the Quantum Biology Centre at the University of Surrey
Year(s) Of Engagement Activity 2022
 
Description Modulating Bioelectricity in cancer towards quantum theapeutics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact A talk to the Quantum Biology Centre at the University of Surrey
Year(s) Of Engagement Activity 2022
 
Description Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Tracking ultrashort carbon nanotubes in NG108 neurons at the Gordon Conference on bioelectonics
Year(s) Of Engagement Activity 2019
 
Description Presentations: Novel strategies to remotely control bioelectronic systems. RSC 6th Analytical Biosciences Early Career Researcher Meeting. Cambridge, UK, 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Presentations:
Novel strategies to remotely control bioelectronic systems. RSC 6th Analytical Biosciences Early Career Researcher Meeting. Cambridge, UK, 2019
Year(s) Of Engagement Activity 2019