Implantable Microsystems for Personalised Anti-Cancer Therapy

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Engineering

Abstract

Cancer is a well-known and much-feared killer disease, accounting for over a million deaths each year in Europe alone. Currently, radiotherapy and chemotherapy are the primary forms of treatment. They are delivered on a regular (often weekly) schedule based on the experience of clinicians and the availability of equipment and staff for treatment, to locations that are determined by the results of CT or MRI scanning. Chemotherapy is generally administered systemically, either as an injection or orally and thus affects regions of the body that have nothing to do with the tumour.
IMPACT(*) will develop tiny silicon chips to be placed inside the patient's body, close to a tumour to measure the cancer's "activity" very precisely in both space and time. The chips will measure simple quantities such as acidity, temperature and oxygen concentration and also more complex and difficult quantities such as the levels of particular proteins that indicate the status of the tumour and the death of cancer cells within it. They will concentrate on measuring the tumour's current vulnerability to radio- and chemo-therapy, and thus where and when that therapy should be targeted. With this knowledge, radiotherapy can be delivered to the right place and the right time to do maximum damage to a tumour. Similarly, by further developing a miniaturised, on-chip drug-delivery capability to protect its sensors from "biofouling", IMPACT paves the way for systems that can also administer chemotherapy to the right place and at the right time.
The work in IMPACT is therefore designed to meet a clinical priority that has been stressed by cancer specialists. The scientific and technical challenges are, however to Chemists and (silicon) Engineers. Sensors must be developed, many of them entirely novel, which make the correct measurements. These sensors must then be placed on silicon, with all the support circuits, wireless communications and safety features that this implanted medical diagnostic and therapeutic system needs.
IMPACT is therefore led by a team of engineers, chemists and both medical and veterinary clinicians. It also includes social scientists, as its results have the potential to revolutionise the way in which cancers are treated. IMPACT's implication is that the timing and location of treatment will be highly patient-specific. Careful consideration of the ethics, risks and regulation of such technology is vital from its inception as IMPACT's success will challenge both patients' perceptions and the organisation and scheduling of therapy.

It will also save many lives.

(*) Implantable Microsystems for Personalised Anti-Cancer Therapy.

Planned Impact

Clinical, translational research in radiotherapy is a current priority of the UK Cancer Research Institute and IMPACT's beneficiaries are cancer patients, doctors and drug companies, in the context of many common malignancies. Radiotherapy is currently delivered in small equal daily doses over several weeks, according to a schedule based on availability of service. IMPACT will allow both dose and timing to be personalised to the biology of a patient's tumour, reducing cancer mortality and NHS costs dramatically. If proof of principle is shown in animals, IMPACT will ultimately lead to randomised clinical trials in which patients would be invited to participate to establish high level evidence of clinical and cost effectiveness compared to standard care.
Clinicians and oncologists of both human and animal patients are CIs on this project. To maximise the speed with which IMPACT's results can move through clinical trials and into real usage, IMPACT will develop focus groups to explore patients' views and concerns about implantable devices to prepare for clinical testing. We will also consult existing patient advocacy groups on these issues. Cancer treatment is an emotive subject that is of enormous public interest. It is vital that a project with IMPACT's aims communicate its work to the public and to decision-makers, without creating expectations of an imminent miracle cure. We have therefore asked for specific funding for training in public communications to prepare the researchers employed on IMPACT to undertake both casual public engagement on their work and also to be available for wider media engagement (e.g. at Science Festivals). To ensure effective and efficient impact, we will; (i) hold an open workshop in years 2 and 4 of IMPACT (ii) access creativity@home to facilitate lateral thinking within the project team and with workshop participants with respect to IMPACT's research and its wider impact (iii) disseminate the acquired multi-disciplinary skill and knowledge of the team via science festivals, laboratory visits (iv) produce a series of short, web-mounted video clips to be produced in which researchers explain their work in an accessible manner to promote collaboration and public understanding.

The commercial impact of a new technology that is (a) mass-produced and (b) widely applicable to a range of cancers will be significant. Implantable sensor chips can be manufactured as a generic underlying silicon platform technology with different sensors and possibly form factors for different cancers. Additional potential commercial developments include stereotactic devices to implant the biosensors, novel biomarkers, imaging technologies to verify their position and radiotherapy planning software and linear accelerators adapted to exploit patient-specific biological data. Throughout the project, we will consider patent protection for individual elements (eg sensors) and for the platform technology with a view to either licensing to a major biomedical vendor or company spinout. In anticipation of such commercial development and to fully explore commercial potential we will require translation funding. Working in partnership with the University of Edinburgh's research & commercialisation/technology transfer office, who seek to promote research and commercialisation activities to potential research sponsors and collaborators, licensees or investors, an exploitation plan will be put in place, that will be regularly reviewed and updated during the course of the project and commercial development opportunities explored in the later part of the project. Existing relationships with Cancer Research UK (in Edinburgh) provide a direct conduit to wider medical collaboration and also to exploitation through organisation and companies involved the production of cancer-treatment equipment and drugs.

Publications

10 25 50
 
Description Sensors can be made that make measurements of (cancer) tumour activity that are sufficienty accurate to guide and thus improve therapy. The materials in the sensors are biocompatible and the sensors can be implanted using a biopsy needle. Sensors have been trialled in animal models (rat, sheep and pig) succesfully. The sensors are not damaged and their readings are not affected by sterilisation and radiotherapy. Sensor shave been developed for several biomarkers and we now have the capability make sensors for many other interesting biomarkers of cancer and other conditions.
We have developed a wireless power and communications system, based on RFID tagging technology, that allows the sensors, when they reach clinical trials and usage, to be wireless, thus allowing mupltiple sensors to be deployed on a single tumour.
We have also shown that these sensors can be used to monitor the progress of both internal and external wound healing.
Finally, we have developed technologies for (a) storing chemotherapy on a chip and releasing it in a controlled manner and (b) "switching on" a biologically-inert "chemotherapy prodrug" local to a tumour, in both cases damaging the cancer while minimising the toxic effect (eg hair loss) of chemotherapy.
Exploitation Route We are:-
1) Bidding for funding to put IMPACT's sensor/radiotherapy system into clinical trials.
2) Developing sensors to monitor wound healing after a bowel resection operation (often for colon cancer)
3) Developing the chemotherapy release/activation work for clinical trials.
Sectors Agriculture, Food and Drink,Chemicals,Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://impact.eng.ed.ac.uk/
 
Description Bowel & Cancer Research Small Grant
Amount £20,890 (GBP)
Organisation Bowel & Cancer Research 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2019
 
Title Carbon Electrode Test Structures and Electrochemical Results 
Description 1. Electrical sheet resistance data from micro-fabricated conductive carbon test structure prepared from standard photoresist materials. 2. Electrochemical characterisation of carbon micro electrodes prepared using the same processes as used for electrical test structures. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
 
Title Data associated with manuscript: A tripod anchor offers improved robustness of peptide-based electrochemical biosensors 
Description Data associated to manuscript. Includes set of tables containing the data used for obtaining figures and results. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data associated with manuscript: Electrochemical sensing of human neutrophil elastase and polymorphonuclear neutrophil activity 
Description Data associated with the manuscript. "Electrochemical sensing of human neutrophil elastase and polymorphonuclear neutrophil activity". Design and evaluation of a peptide-based electrochemical biosensor for HNE activity detection. The analytical characteristics of the sensor were evaluated. The platform was applied for the detection of HNE in real blood samples. Dataset includes set of tables containing the data used for obtaining figures and results. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Description Anastomotic Tissue Oxygenation Monitoring in Clinical Practice - ATOMIC 
Organisation NHS Lothian
Country United Kingdom 
Sector Public 
PI Contribution Over 20,000 large bowel anastomoses are performed each year in the UK. Anastomoses can have a leak rate of 10%. A leak is a serious surgical complication. Delay in treatment has significantly deleterious effects on survival. There are also significant quality of life and health economic consequences. [2] The ACPGBI and NIHR HTC have identified research into anastomotic leak as a priority. Initial signs of a leak can be subtle. A method that can detect a leak early, and reliably, would have enormous clinical value. Current research focuses on tissue perfusion at the time of surgery and suggests measuring tissue oxygen concentrations is beneficial [3]. Tissue oxygenation is currently not measured postoperatively. Our hypothesis is: microchip sensors placed adjacent to the anastomosis at the time of surgery will provide vital data in the post-operative period to help predict and prevent leaks. It is envisaged that these data would be presented, in real time, with data on existing ward monitoring systems. This would provide a richer and more accurate insight into the patient's condition than any single data source.
Collaborator Contribution Using a recognised porcine model of bowel ischaemia and anastomotic leak protocol and sensor evaluation are being performed on three control subjects. These will test sensor function on normal gut, ischaemic gut, intact and leaking anastomoses. Three experiments would be performed using sensors on normal gut and adjacent to intact an anastomosis which is made to leak after 24 hours and monitored for 48 - 96 hours. These data will be compared to normal physiological data obtained at the same time.
Impact Submitted to the British Journal of Surgery Validation of a Miniaturised Electrochemical Oxygen Sensor for Measuring Intestinal Oxygen Tension in Clinical Applications Mark E Gray a,b,*, Jamie R K Marland c, Camelia Dunare c, Ewen O Blair c, James Meehan b,d, Carol Ward a,b, Simon P Langdon b, Andreas Tsiamis c, Ian H Kunkler b, Alan F Murray d, David Argyle a, Alex Dyson e, Mervyn Singer e, Mark A Potter f Disciplines involved - Engineering Chemistry Vet Medicine Medicine Cancer biology
Start Year 2018
 
Description Assessing a Wound Dressing - Visualisation for optimal Intervention using Sensor Evidence (ADVISE ME) 
Organisation NHS Lothian
Country United Kingdom 
Sector Public 
PI Contribution Development of miniaturised, wireless sensors for oxygen, pH and other biomarkers of wound status
Collaborator Contribution Knowledge of wounds, their healing problems and a conduit to human trials, following animanl model trials.
Impact None as yet - the collaboration is still forming
Start Year 2018
 
Title Biomarker sensor for implant 
Description Electrochemical sensors - miniaturised for implant purposes and capable of detecting a wide range of biomarkers. Specific sensors have been develped for Caspase, pH and HNE, all of which are related to cancer. The sensors have been trialled successfully in large-animal (sheep) models. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact Seeking funding for further development and clinical trials. 
URL https://impact.eng.ed.ac.uk/
 
Title Miniaturised Clark Electrode and ISFET sensors for implantation 
Description Miniaturised Clark Electrode and ISFET sensors for implantation ... designed to monitor cancer biology but able to measure other paremeters for other conditions. The sensors have been trialled successfully in small (rat) and large-animal (sheep) models 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact This will form the basis of the next project that will include clinical trials. 
URL https://impact.eng.ed.ac.uk/
 
Description Talk at the Mason Institute, University of Edinburgh on 29 January 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Talk on 'Diagnosis, Delivery and Direction - Implants Using New Technologies' at a public symposium titled 'Implanting Technology: Smart Moves from an Engineer, Ethicist and Philosopher'
Year(s) Of Engagement Activity 2013
 
Description BREAST CANCER PATIENTS' VIEWS ABOUT IMPLANTED BIOSENSORS at 3rd Annual Scientific Meeting of the Scottish Radiotherapy Research Forum - Stirling 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr Theresa Ikegwuonu presented a poster 'BREAST CANCER PATIENTS' VIEWS ABOUT IMPLANTED
BIOSENSORS' at the 3rd Annual Scientific Meeting of the Scottish Radiotherapy Research Forum - Stirling on 23 October 2014
Year(s) Of Engagement Activity 2014
 
Description Edinburgh International Science Festival at the National Museum of Scotland 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact IMPACT took part in the University of Edinburgh's Family Events Programme, part of the Edinburgh International Science Festival activities held at the National Museum of Scotland from 1-16 April. Between 11-16 April researchers from the IMPACT project reached over 2000 people, who enjoyed a variety of activities at the Learning Centre. Our 'Micro-Engineers' event invited children and their carers to discover real life plans to implant a miniature monitoring station inside a cancer tumour to help doctors destroy it. They learned about sensors and used some common ones found at home and in hospitals. The children were also able to light up an LED attached to a chip by dipping a rod into a 'body' tank, showing how the IMPACT device will be powered when inside the body. Visitors to the exhibit also enjoyed a 'spot the difference' poster activity to teach the difference between healthy and cancerous cells, before looking down microscopes and testing their knowledge on both types of cells.
Year(s) Of Engagement Activity 2017
URL https://www.impact.eng.ed.ac.uk/about/news/20170427/impact-project-edinburgh-international-science-f...
 
Description Healthcare Technologies Showcase Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Multicorder, IMPACT, Proteus, and Sonopill, research programmes are coming together to hold a joint one-day conference on 18 April 2018 to share experiences, expertise and best practice. In the evening we plan to introduce our work to MSPs at Holyrood.
Year(s) Of Engagement Activity 2018
 
Description Implantable Microsystems for Personalised Cancer Therapy - invited talk at 11th VDEC D2T meeting in Tokyo, Japan on 21 September 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Dr Stewart Smith gave an invited talk at this meeting.
Year(s) Of Engagement Activity 2016
URL http://www.vdec.u-tokyo.ac.jp/d2t/D2Tsymposium2016-abstract.html#S1-2
 
Description Innovation in Cancer Care - talk at The New Club, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Ian Kunkler gave an invited talk at The New Club, Edinburgh on 20 June 2015
Year(s) Of Engagement Activity 2015
 
Description Invited Intl Lecture - St Gallen Intl Consensus Conference -Technical innovation in adjuvant radiotherapy: evolution and evaluation of new treatment.  
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Prof Ian Kunkler gave an Invited Intl Lecture: St Gallen Intl Consensus Conference. Vienna, 20 March 2015 on Technical innovation in adjuvant radiotherapy: evolution and evaluation of new treatment. 
Year(s) Of Engagement Activity 2015
 
Description Invited presentation: Scottish Radiotherapy Research Forum, 6 November, 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Professor Alan Murray spoke about the IMPACT project at this invited presentation at the Scottish Radiotherapy Research Forum, 6 November, 2015
Year(s) Of Engagement Activity 2015
 
Description Keynote: Eurobiosensors 2016: 5th Euro Biosensors and Bioelectronics Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Professor Mark Bradley gave the keynote at this conference. His talk was titled 'Electrochemical detection of protease activity' and highlighted the work of the IMPACT project.
Year(s) Of Engagement Activity 2016
URL https://biosensors.conferenceseries.com/europe/2016
 
Description Scottish Breast Cancer Trials Unit annual conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact talks given by several team members from IMPACT (Prof Ian Kunkler, Prof David Cameron and Prof Alan Murray in 2014 and by Prof Alan Murray and Dr Bill Nailon in 2013)
Year(s) Of Engagement Activity 2013,2014
 
Description Seminar at Dundee University on 2 Apr 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Seminar at Dundee University on 2 Apr 2014
Year(s) Of Engagement Activity 2014
 
Description Seminar at the University of York on 22 May 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Seminar at the University of York on 22 May 2015
Year(s) Of Engagement Activity 2015
 
Description Seminar to a mixed clinical/scientific audience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Seminar to a mixed clinical/scientific audience at Ninewells Hospital, Dundee to present 'Implantable Systems for Personalised Anti-Cancer Therapy.'
Year(s) Of Engagement Activity 2017
 
Description Sensors for Cancer 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Talk on 'Sensors for Cancer' at the CDT Conference (Integrative Sensing and Measurement) at the University of Edinburgh
Year(s) Of Engagement Activity 2015
 
Description Several IMPACT team members presented talks at this NIHR Colorectal Therapies HTC's National Meeting 2015  
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Mark Potter, clinician, Prof A Murray and Hugh Paterson all participated in the meeting.
Year(s) Of Engagement Activity 2015
 
Description Speaker at Bioelectronics and Biosensors Congress 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Dr Stewart Smith was a speaker at the Bioelectronics and Biosensors Congress 2016 held in London.
Year(s) Of Engagement Activity 2016
URL http://www.rsc.org/events/detail/23104/bioelectronics-and-biosensors-congress-2016
 
Description Talk on Diagnosis, Drug Delivery and Direction Implants and Cancer. Students at Kirkaldy High School, Kirkaldy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk - 'Diagnosis, Drug Delivery and Direction Implants and Cancer' to c.50 students over 3 classes at Kirkaldy High School, Kirkaldy
Year(s) Of Engagement Activity 2014,2015
 
Description The Future of Medicine - Technology and the Role of the Doctor in 2025 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The aim of this conference is to explore just how far the delivery of health and care has been improved by the availability of new technology, and what the latest predictions are by those working in the field of how medicine will really be practised in ten years' time. 3 of the IMPACT team attended, with Prof Alan Murray and Prof Ian Kunkler both giving talks and Dr Eva Gonzalez-Fernández presenting a poster. This was a joint conference of the Royal Society of Medicine and the Institute of Engineering and Technology which took place in London.
Year(s) Of Engagement Activity 2015
 
Description Visit by young people from Muirhouse, Edinburgh, to the Scottish Microelectronics Centre 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit by young people from Muirhouse who visited the Scottish Microelectronics Centre to learn more about biosensors for the film that they are creating about how it feels to have either living or non-living materials placed in the body.
Year(s) Of Engagement Activity 2016
URL https://animalmechanicalandme.com/