Cambridge CiC 2018: Converting innovative science into human health benefit

Lead Research Organisation: University of Cambridge
Department Name: UNLISTED

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The Confidence in Concept (CIC) scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions to flexibly support a portfolio of early stage translational research projects. CIC is designed to accelerate the transition from discovery research to viable translational projects by supporting preliminary studies to establish proof-of-concept so that the approach will then become competitive for more substantial translational funding.

People

ORCID iD

 
Description A novel transcatheter valve for younger patients with aortic stenosis
Amount £248,018 (GBP)
Funding ID TG/15/4/31891 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
 
Description ACT Emergency appeal
Amount £24,956 (GBP)
Funding ID 900250 
Organisation ACT Alliance 
Sector Charity/Non Profit
Country Switzerland
Start  
 
Description Cambridge Cardiology: Developing Catheter-based Treatments for Valvular Heart Disease
Amount £60,000 (GBP)
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 02/2018
 
Description Cambridge Enterprise Post-doctoral business plan competition
Amount £5,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start  
 
Description Cell surface biomarkers to predict outcome of COVID-19 upon hospital admission
Amount £50,000 (GBP)
Organisation Addenbrooke's Charitable Trust (ACT) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2020 
End 09/2022
 
Description Development of a Transcatheter Mitral Repair System for patients with Mitral Regurgitation
Amount £69,978 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Development of a novel polymeric trans-catheter aortic valve to improve durability in high-risk patients: proof of concept study
Amount £65,641 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description EPSRC Impact Acceleration Account Follow-on Fund University of Cambridge
Amount £50,000 (GBP)
Organisation ESRC Impact Acceleration Account Cambridge 
Sector Academic/University
Country United Kingdom
Start 08/2019 
 
Description Minimally invasive Spinal Cord Stimulator (MI-SCS):validation experiments in human spine cadaveric model
Amount £40,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2019 
 
Description NIHR i4i Connect CYPMH theme
Amount £150,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2022 
End 12/2023
 
Description NIHR, I4I PDA
Amount £1,600,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR i4i Invention for Innovation (i4i) Programme
Sector Public
Country United Kingdom
Start 12/2021 
 
Description Preliminary whole cell lysate analysis experiments
Amount £50,000 (GBP)
Organisation Addenbrooke's Charitable Trust (ACT) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2020 
End 09/2022
 
Description R9.5 Development of a novel audiology computer application and modified headphone system for the DigiScreener sensory screening platform
Amount £70,000 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Confidence in Concept Scheme
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 05/2020
 
Description Targeting cell death by ferroptosis in Parkinson's disease
Amount £20,039 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Confidence in Concept Scheme
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Title Therapeutic targeting of chromosomal instability in cancer 
Description • Isolation of intact tumour cells from FFPE using the CellenONE instrument (protocol available on request). • Prototype FFPE single cell isolation protocol complete (available on request). • Prototype fresh frozen single cell isolation (tumour tissue and ascites) protocol complete (available on request). • Prototype library preparation protocol complete (available on request) for different tissue types: FFPE, fresh frozen and cell lines. • Reference dataset generated for single cells at different ploidy and cell cycle states to improve the copy number calling for each cell. 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? No  
Impact Milestone 1: genome-wide copy number profiling of gold-standard test samples (completed) Shallow whole genome sequencing of cell lines: CIOV1, PEO1, OVCAR3, NA12787 and tumour FFPE tissue test samples was completed. Milestone 2: comparison of whole-genome amplification and library preparation reagents (completed) 1. Isolation of nuclei and single cells from FFPE material: During the course of this grant we realised that isolation of single cells rather than nuclei was indeed possible from FFPE tissue. Furthermore, we also found that the proportion of ovarian tumour cells with micronuclei were not well characterised with single nucleus preparation, with crucial genomic information being lost. Isolation of the whole intact tumour cells has the advantage of containing all genomic information but also getting more information about the specific cell properties and its morphology (elongation, size, circulation). We successfully established protocol to isolate intact tumour cells from clinical FFPE tissues based on the Bolognesi methodology [PMCID 26864208] and optimise the method for the single cell identification (using nuclear marker - DAPI, tumour positive marker - cytokeratin and non-tumour positive marker - vimentin) and dispensation onto two plates formats: 96 and 384 well plate format using CelleOne instrument. Isolated intact cells from FFPE tissue using CellenOne instrument (channels: transmission, DAPI, cytokeratin and vimentin). 2. Optimisation of the shallow whole genome library prep for single cells isolated form FFPE tumour tissue: During the course of this grant we realised that the whole genome amplification reagents Sigma and Picoplex V1, and associated library kits NEB and Nextera flex, were not optimal and introduced noise compared to the Smarter PicoPlex Gold Single Cell DNAseq kit (Takara). Therefore, we put effort to test and optimise the workflow using Smarter PicoPlex Gold Single Cell DNAseq. Additionally, as ~70% cells from the initial sequencing runs showed poor data quality we also focused on improving the copy number calling for each cell by generating datasets for single cells at different ploidy and cell cycle states. We successfully optimised single cell whole genome library preparation using Smarter PicoPlex Gold Single Cell DNAseq kit (Takara) kit from FFPE tissue. Generated libraries showed no significant allele dropout and good data quality. Absolute copy number comparison between CIOV1 FFPE (A, C) and CIOV1 FF (B, D) and clinical FFPE (E). We successfully optimised sequencing conditions for single cell whole genome library preparation from FFPE tissue. We found that by adding 20% of PhX reference genome to the sequencing reaction significantly improved the data quality. We successfully generated a catalogue of shallow whole genome sequencing datasets from single cells at different ploidy and cell cycle. We selected four cell lines to generate high quality data to train the algorithm to improve single cell data analysis: normal diploid cell line (NA12787), tumour diploid cell line (PEO1), tumour diploid cell line with losses/haploid (CIOV1), triploid cell lin. All cells from cell lines were FACS sorted to obtain three populations: cells at G1, S and G2/M cell cycles. Single cells from all three populations were then isolated using CelleOne instrument and underwent optimised single cell whole genome library preparation using the Smarter PicoPlex Gold Single Cell DNAseq method and sequenced. Milestone 3: observing the effect of DNA repair enzymes (not performed) This was not performed as the current single cell whole genome library prep was optimised for FFPE samples without the need of using the DNA repair system. Milestone 4: reagent dilution and cost reduction (completed) During the experiments outlined under milestone 2 we tested 4x and 5x dilution and achieved accurate results. We successfully optimised the workflow for the single cell whole genome library preparation using Smarter PicoPlex Gold Single Cell DNAseq kit (Takara) kit on Mosquito robot from FFPE tissue. Our current optimised workflow uses 5x dilution reagents on a 384-plate format using automated Mosquito robot. The whole workflow from start to finish takes XX hours: single cell isolation (6hours), cell dispensing (4 hours), library preparation and sequencing (10hours + 16hours) and data analysis XX hours (under development). 
 
Description Artemis with Cambridge Enterprise 
Organisation University of Cambridge
Department Cambridge Enterprise
Country United Kingdom 
Sector Academic/University 
PI Contribution Cambridge Enterprise (CE) helps with commercialization of our mental healtyh assessment platform.
Collaborator Contribution We have developed platform for online assessment of mental Health. It uses innovative adaptive testing technology and tjhus is way more efficient compared to standard mental health assessment.
Impact IP protection research, proposal for funding (MRC), development of business model
Start Year 2021
 
Description Artemis-R 
Organisation Effusion LLP
Country United Kingdom 
Sector Private 
PI Contribution this is a small tech company who helped us develop the website and app - we have gone on to work with them in follow on funding (we just got NIHR funding to test Artemis-A in schools on a bigger scale) and Jo Anderson is working with them in a different project
Collaborator Contribution N/A
Impact N/A
Start Year 2021
 
Description developing the Artemis-R logo and visual identity 
Organisation Effusion LLP
Country United Kingdom 
Sector Private 
PI Contribution We are collaborating with Effusion - a digital and design studio. We have been working with Effusion on developing the Artemis-R logo and visual identity, as a part of an ongoing development of the brand's identity. Backend of Artemis-A is developed in collaboration with the Psychometric Centre, Cambridge.
Collaborator Contribution There is a contract in place and once the wok is finalised Effusion will transfer the copyrights for design to the University.
Impact We are working with them in relation to STEP. The website and app - papers to come but nothing yet. And the Artemis-A app itself?
Start Year 2019
 
Title Methods and Apparatus for Direct Annuloplasty 
Description Detailing the annuloplasty prosthesis and the method of its insertion and adjustment. Now lapsed 
IP Reference PCT/GB2017/053326 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact Surgical prototype complete and tested in dead hearts. Trans-catheter prototype designed and parts purchased, awaiting assembly. Some beating heart experiments have been performed in the laboratories of LifeTec Group, Eindhoven under a standard CRO agreement. These demonstrated the viability of the device and its implantability in a beating heart, but not in a living animal. Unfortunately, further funding was not obtained, and so implantation in a living animal has not been tested. Due to funding not being obtained (notably MRC DPFS), the team has dispersed making the project hard to continue. Cambridge Enterprise have now allowed the relevant patent to lapse. Other devices in the mitral space are also now advancing rapidly. These factors mean that translation to the clinic is now unlikely.
 
Title DigiBel 
Description The award was made in August 2019 and the funding available for use from late September, following a successful start to the coding there were major delays (4-5 months) in accessing grant funding following administrative changes in the University finance structure. Subsequently Covid restrictions have delayed clinical validation. Further funding to enable recoding of DigiBel as a web-app was awarded from ACT in addition to funding to undertake CE marking (MDD Class 1). CE marking is now in process using Global Regulatory Services Ltd. A service evaluation study registered at CUH has enables early usability and comparison to standard audiometry. Following CE marking, IRAS application will be made to enable formal clinical validation in the ENT department. Collaboration with Mr James Tysome and Prof Manohar Bance is planned to test DigiBel for conditions such as Meniere's disease in addition to use as a screening device. 
Type Products with applications outside of medicine
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2020
Development Status Under active development/distribution
Impact Louise Allen has formed a start up company Cambridge Medical Innovation Ltd. to commercialise DigiBel following CE marking and clinical validation. The low cost of running Digibel on a standard iPad tablet make it suitable to be used as a standalone hearing testing web-app to be used by patients to monitor their hearing at home and in the community. DigiBel screening test will be teamed up with DigiVis vision screening test as an integrated school screening device which requires no expertise to administer. DigiBel could prove to be a useful tool in screening vision and hearing in LMICs. It runs on standard ipads with relatively cheap headphones. Good internet links which are often available even in rural areas in LMIC countries. 
 
Title DigiBel as a web-app was awarded from ACT in addition to funding to undertake CE marking (MDD Class 1). 
Description A pilot service evaluation study (which has been already been registered at CUH to compare measurements and usability of DigiBel to standard audiometry) will be undertaken. The major potential application for DigiBel is its use for screening in primary school age children and in the identification of children who would benefit from bone conduction hearing loss. The low cost of running Digibel on a standard iPad tablet make it suitable to be used as a standalone hearing testing web-app to be used by patients to monitor their hearing at home and in the community. DigiBel screening test will be teamed up with DigiVis vision screening test (now commercialised) as an integrated school screening device which requires no expertise to administer. 
Type Therapeutic Intervention - Complementary
Current Stage Of Development Initial development
Year Development Stage Completed 2022
Development Status Under active development/distribution
Impact The affordable and child-friendly DigiVis and DigiBel apps will enable screening in more children both in the UK and in developing countries. There has already been interest from Unicef regarding the use of both tests in their projects across the world. 
URL http://www.digibel.co.uk
 
Title The Chronic trial intraoperative echo confirming placement and functioning 
Description Five animals were implanted in early September 2018, with intraoperative echo confirming placement and functioning. Implantation time was under 1 minute in all cases. Intraoperative imaging showed adequate position and leaflet motion. Blood panels were unremarkable. Unfortunately, 4 out of 5 animals died within 14 days of implantation. Autopsy revealed severe thrombosis covering the proximal and distal surfaces of these valves. It appears that all animals had significant pulmonary insufficiency, leading to acute heart failure in 4 out of 5 cases. There were instances where leaflets failed to open and/or there was not complete coaptation at the centre of the valve. Taken together, the negative outcome was the result of turbulent flow due to poorly manufactured leaflets and not the device frame, materials or procedure. The surviving animal completed the 180-day follow-up period 
Type Therapeutic Intervention - Medical Devices
Year Development Stage Completed 2018
Development Status Actively seeking support
Impact Effective encapsulation of the alloy in a bio-compatible polymer proved more difficult than hoped, which delayed the project. Integration into a trans-catheter system has also been more difficult than hoped, resulting in a trans-apical or surgical approach being required, rather than trans-femoral. 
 
Title Development of a novel hearing computer application and modified headphone system for the DigiScreener sensory screening platform 
Description EG technology Ltd. undertook the initial coding work, developing the screening and threshold hearing test under instruction and following British Society of Audiology standards. This was coded as a windows app to be used on a laptop computer using a specific set of headphones and was completed in January 2020. Covid hit a few months later and we determined the need to have a test which could be undertaken as a web-application on a standard iPAD with a cheaper set of headphones - compatible with home use and monitoring. Although numerous on-line hearing tests and apps exist, these are non-standardised or CE marked, making them inappropriate for clinical decision making. The innovative approach of the new web-app, now called DigiBel includes: 1) web-app use to enable home use and self-testing by patients from 4 year and over 2) initial automated assessment of ambient noise level 3) accurate calibration of ipad system microphone and sound output by Institute of Sound and Vibration research in Southampton University 4) Conditioning pre-test to ensure patient understanding 5) configurable screening and threshold tests (frequency / tone type / screening standard) with child friendly options 6) bone conduction headphone testing facility 7) Feed back regarding test performance - false positive responses to aid clinical evaluation The second prototype was developed following accurate calibration of the system (4 different generations of ipad and the chose air-conduction headphones) at the ISVR as planned 
Type Of Technology e-Business Platform 
Year Produced 2020 
Impact Covid-19 and the large backlogs in audiology have hampered clinical validation studies. DigiBel v1 is now live at www.digibel.co.uk . Following the validation studies the web-app will be licensed from Cambridge commercialised within the same portfolio as DigiVis (www.digivis.org) by CMI Ltd to give an affordable solution for vision and hearing screening in the UK and internationally. 40% of Local Authorities do not undertake the recommended Reception year school vision screening and 60% do not undertake hearing screening and yet 20% of children suffer from visual disorders such as amblyopia which require early detection to treat and many children are labelled as poor achievers due to hearing impediment which could be mitigated by the use of bone conduction headphones during class. The affordable and child-friendly DigiVis and DigiBel apps will enable screening in more children both in the UK and in developing countries. There has already been interest from Unicef regarding the use of both tests in their projects across the world. 
URL http://www.digibel.co.uk
 
Title The UI/UX design - Artemis-A 
Description Procedure: Members of the app development team attended to demonstrate the app and collect feedback about the design and navigation preferences. At the start of each session, participants were given a demonstration of the CAT platform to show how items are selected from the bank of measures. Following this, the app development team presented three visual mock-ups for both mobile and desktop platforms using an interactive prototype and print assets. Participants were prompted to give feedback on the 'look and feel' of the app, select the best design and functionality features, and suggest additional improvements. 
Type Of Technology Webtool/Application 
Year Produced 2021 
Impact The Artermis family of tools offer a wide range of applications for the identification of poor mental health to the routine monitoring of outcomes of treatment - this could increase access to services for hard to reach groups who might not identify themselves and needing help, such as children, job seekers etc 
URL https://www.artemis-a.org/
 
Description - CRUK Innovation Summit 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Ania Piskorz presented at the summit highlighting her entrepreneurship activities involving our recently created startup Tailor Bio and our support from the MRC through the CiC award. This activity created awareness of Ania's science in a commercial setting and has expanded our network and opportunities to commercialise the output of this study.
Year(s) Of Engagement Activity 2019
URL https://www.cancerresearchuk.org/funding-for-researchers/research-events-and-conferences/innovation-...
 
Description Artemis-A - School visits (e.g Landmark International School, Fulbourn; School visit (Soham Village College, Soham) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact We have presented the Artemis-A and talked about the project in four secondary schools in the area (Cambridge, Ely).
These engagement activities were integral to the development of the app but also for informing plans to for how it would successfully be applied within secondary schools for the next stage of the project
Year(s) Of Engagement Activity 2019
 
Description Artemis-R 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact this is a network of researchers and practitioners who were interested in supporting mental health in schools.
These engagement activities were integral to the development of the app but also for informing plans to for how it would successfully be applied within secondary schools for the next stage of the project.
Year(s) Of Engagement Activity 2020
 
Description CRUK Single Cell Workshop in Southampton 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Here we presented some preliminary results on using our protocol to explore ongoing chromosomal instability in ovarian cancer cell lines. The presentation was well received and provided validation of our approach for research use.
Year(s) Of Engagement Activity 2019
URL https://www.eventbrite.co.uk/e/single-cell-analysis-in-cancer-a-workshop-tickets-64716482742?utm_cam...
 
Description Cambridge Children's Hospital presentation DigiBel and DigiVis at the University of Cambridge Alumni meeting 24th September 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Due to Covid 19 Restriction DigiBel and DigiVis was an international on-line webinar reaching over 200 University Alumni.

DigiBel and DigiVis were presented by Louise Allen This was an introduction to DigiBel as a hearing web-app which enables community screening and testing of children's hearing Its use in Low and Middle income countries as welll as in the UK was discussed. There was a live on-line Q & A session which covered the innovation.

The impact of this meeting was to introcue the concept of self-testing to enable early detection of treatable sensory issues in children and highlight innovation within out NHS trust.
Year(s) Of Engagement Activity 2021
 
Description Centre33 quarterly staff meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation of the project to a CPD session for Centre 33 practitioners. These engagement activities were integral to the development of the app but also for informing plans to for how it would successfully be applied within secondary schools for the next stage of the project
Year(s) Of Engagement Activity 2019
 
Description DigiBel and DigiVis - Innovation and technology show July 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact DigiBel and DigiVis were presented by Louise Allen at the Institute for Government and Public Policy Healthcare Innovation and technology show July 2021 watched by 450 attendees
Year(s) Of Engagement Activity 2021
 
Description DigiBel and DigiVis presentation Eastern Academic Science Network Innovation panel 15th October 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact This was a 20 minute presentation to 20 members of the Innovation panel for EAHSN to determine if they would support adoption of DigiBel . EAHSN decided to support adoption of DigiBel and application to the National Innovation Accelerator. EAHSN decided to support adoption of DigiBel and application to the National Innovation Accelerator.

Most significant outcome: support for adoption of DigiBel in the Cambnridgeshitre and Peterborough integrated care system
Year(s) Of Engagement Activity 2021
 
Description DigiBel presentation to UNICEF representatives in South America, Africa and the Middle East 17th September 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact This was an hour long presentation to UNICEF leaders in the field of sensory screening from across the world to determine the role that DigiBel might play in school screening. There was much interest about the potential for using the web-app. Following validation UNICEF have demonstrated that they are interested in using the service.
Most significant outcome: Potential for UNICEF to adopt the technology for their projects internationally.
Year(s) Of Engagement Activity 2021
 
Description FullScope Consortium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Discussions with Centre 33 - FullScope Consortium senior staff as well as presentations of the work and plans to their practitioners.
These engagement activities were integral to the development of the app but also for informing plans to for how it would successfully be applied within secondary schools for the next stage of the project
Year(s) Of Engagement Activity 2014,2020
 
Description The NIHR Applied Research Centre (ARC) East of England 
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 These engagement activities are integral to the development of the app but also for informing plans to for how it would successfully be applied within secondary schools for the next stage of the project
Year(s) Of Engagement Activity 2021