Impact case study database

Over 2,100,000 new cases of breast cancer are diagnosed annually around the world. In almost all cases, surgery is required to remove the tumour. To determine whether the disease has spread to other sites, the European Organisation for Research and Treatment of Cancer (EORTC) currently recommends sentinel lymph node biopsy (SLNB), wherein the sentinel lymph nodes are removed and inspected under a microscope. The procedure provides certainty regarding the localised or metastatic state of the cancer, which informs the post-surgery treatment pathway, and leads to an overall improvement in outcomes.

Despite this minimally invasive procedure being the preferred standard of care in breast cancer operations, current methods of sentinel node detection are not easy to use as they involve injection of radioactive isotopes with a blue dye as a tracer. Because the isotopes are potentially hazardous they must be injected in the nuclear medicine department, rather than by surgeons, and the isotopes’ six-hour half-life presents challenges and limitations for theatre scheduling. Mandatory handling and waste disposal regulations add to the overheads, as does the training and licensing of operating theatre staff in the handling of radioisotopes. Furthermore, patients themselves may have reservations about the use of nuclear medicine. Together, these factors present a significant barrier to the widespread adoption of SLNB. For hospitals or clinics without ready access to radioisotopes, SLNB is not performed at all.

The research at UCL by Pankhurst and his team led to the realisation of a hand-held probe capable of working at the unprecedented levels of sensitivity and selectivity required for the SLNB application. This innovation has had direct and significant impacts in the field through the commercial production of the award-winning Sentimag device and the Sienna+/Magtrace tracer ( S1). The magnetic approach to SLNB is straightforward: the Sentimag is a direct replacement for the Geiger counter, and the Sienna+/Magtrace is a direct replacement for the radioisotope – and minimal clinician training is required for its adoption. Sienna+/Magtrace has a shelf life of three years, enabling its use much more widely than just at centres with access to nuclear medicine. The new technology pioneered from UCL – compared to the incumbent standard-of-care use of radioisotopes – presents fewer staff safety issues, and a lower regulatory burden. As such it significantly overcomes the barriers to uptake inherent in the current approach and makes SLNB available to all.

In 2006-07, based on its success in early clinical studies, Pankhurst’s SentiMag was developed “from bench to clinic” . With seed investment from UCL Business plc and others, Endomagnetics Ltd was formed as a spin-out company in April 2007. Between 2008 and 2010, the Technology Strategy Board supported a collaborative research project linking Endomagnetics with Integrated Technologies Ltd, a medical devices manufacturer. This resulted in a prototype Sentimag that was first trialled on 160 subjects and subsequently on many hundreds more. The Sentimag and Sienna+/Magtrace products were CE marked in Europe in 2011 and 2012 respectively, and together achieved Investigational Device Exemption (IDE) accreditation in the USA in 2017.

Between 1 August 2013 and 31 December 2020, through Endomagnetics Ltd, the UCL-led innovations have ( S2):

• 60,000+ breast cancer patients treated using the SentiMag and Sienna+/Magtrace medical devices;

• 600+ SentiMag base units and 45,000+ vials of Sienna+/Magtrace sold; resulting in GBP9,800,000 turnover in 2019/20, with 10% year-on-year growth;

• GPB32,000,000 private investment raised;

• 61 full-time jobs created (54 in the UK and 7 in the USA) with a 43%/57% female/male gender balance; plus 11FTE part-time/associated posts generated;

• 51 granted/allowed patents from a family of 21; with 13 in the US;

• ranked 43rd in the 2020 Sunday Times’ Tech Track 100 league table – a ranking of the UK’s fastest-growing tech companies ( S3); and

• receipt, in 2018, of the Queen’s Award for Enterprise ( S4).

Endomagnetics Ltd is now a mature company endorsed by the clinical community “ by moving breast cancer treatment forward and it’s really doing things patients are happy with” – Leading Breast Surgeon, from the University of California, San Francisco ( S5). In 2018 it established a US operation base, with 5 staff permanently based there for sales and marketing.

In 2020 Endomagnetics Ltd has been active in responding to the special challenges brought on by the Covid-19 pandemic. In the UK, the crisis forced breast cancer centres to change their ways of working, in many cases moving from large hospitals to smaller Covid-free facilities. An example of this was the relocation of cancer services from the Greater Manchester region to the Rochdale Infirmary ( S6). Given that these smaller units did not have regular access to nuclear medicine for breast cancer staging, it was vitally important that these affected facilities should be helped so that they could continue to offer access to the best standard of care available.

Endomagnetics stepped in by providing over GBP150,000 worth of free vials of Sienna+/Magtrace to the NHS, plus free guidance and support to anyone that wanted it ( S7). The move has been welcomed by UK surgeons, as evidenced by the testimonials of four of London’s most highly recognised consultant oncoplastic breast surgeons given in response to the establishment of new Covid-free ‘hubs’ in the city ( S8). This promoted “ fantastic cooperation between NHS and the private sector” (Consultant Oncoplastic Brest Surgeon) and has allowed highly recognised consultants to continue working “ in the best possible way … delivering the best-and the faster- possible care” (Oncoplastic Breast Surgeon and Clinical Lead) ( S8).

Human brain imaging is critical for both clinical practice and neuroscience research. The technologies currently in use, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are expensive, immobile and require designated hospital space or research facilities. For example, the systems cannot be used to monitor the brain at the hospital bedside, at home, or in an ambulance. Also, they are unsuitable for studying the brain during a task involving movement, or during human interactions. These systems also require the subject to remain motionless for several minutes during the procedure, inhibiting studies of the developing brain in babies and toddlers. Through UCL-led innovations and commercialisation via a UCL spin-out company, Gowerlabs, the DOT system has been adapted and developed to provide high-quality, real-time images of human brain function in a truly wearable package that is now in use worldwide, both for research and development and by large corporations such Facebook and Apple. The products have generated revenues of GBP2,762,000 to date and are providing new ways to explore brain activity in real time.

Product innovation and application

Building on UCL-led research, Gowerlabs has developed three key product lines:

• The benchtop NTS brain mapping system ( R1)

• The patented, wearable and fibreless fNIRS brain imaging system LUMO ( R3)

• A range of optical phantoms that mimic human tissues ( R5, R6).

The NTS benchtop imaging system has had significant clinical impact and is considered to have “ paved the road towards a new understanding of neuroplasticity mechanisms following reconstructive surgery” ( S1). However, in common with most existing DOT devices, it requires a large number of bulky optical fibres to carry light to and from the head, which limits its possible applications. To address these limitations, Gowerlabs built on the early microNTS work ( R3) to develop the world’s first commercial, high-density, fibreless DOT system, LUMO, which provides significantly higher resolution imaging than any other commercially available DOT device. The system’s novel design enables high-quality images of the brain to be obtained in almost any environment and the products have been used by companies and research institutions in Africa, Australia, China, Europe, UK and the US.

To help DOT device users validate new array designs and assess system performance, Gowerlabs has also developed the world’s first anatomically correct head phantoms. These have proven useful for both companies and clinicians. Vilber Lourmat, a Gowerlabs client, considers Gowerlabs to be “ the only company that can supply optical phantoms of the types we need for our application” ( S2).

Gowerlabs DOT systems are being used in clinical settings (eg Medlink, Australia) R&D settings (eg McMaster University Canada and Vilber Lourmat for cancer research), and by technology companies such as Facebook Reality Labs and Apple for their computer-brain interface research; and other technology companies such as Philips and Kingfar International Inc., China.

Gowerlabs systems has enabled “ modern machine learning techniques to accelerate brain computer interface (BCI) development for many different applications” ( S3) with improved accuracy when measuring brain activity in real time. For example, the application of the LUMO system allowed Facebook Reality Labs research on translating neural activity into text to achieve “ average error rates as low as 3% when tested with vocabularies of up to 300 words” compared to the previously “ limited error rates north of 60% for 100-word vocabularies” ( S3).

The Gowerlabs brain imaging systems have also enabled novel research on new-born babies’ brains, revealing new insights into infant malnutrition and autism, and have been featured in films on social media including Seeing Signs of Autism in Infrared by UCL Engineering (2013) and Brain Imaging Tool Seeks Signs Of Infant Malnutrition by SciDevNet (2015), engaging over 4,000 viewers in the process ( S4). Other coverage of how Gowerlabs DOT systems have been used in cutting edge research include: Brain Imaging Technology Designed for Babies – (November 2020), BBC News website; The Wonderful World of Babies – Episode 2 (2018; [TEXT REMOVED FOR PUBLICATION]); BBC World News Horizons 4, Episode 16 – The Brain (2014); BBC World Service Health Check – Babies’ Minds: The Truth about Life and Death (2014); BBC Horizon – Living with Autism (2014; [TEXT REMOVED FOR PUBLICATION]) ( S4).

Economic impact and sector development

Gowerlabs brain imaging systems have been purchased by technology industry leaders, such as Philips, Apple and Kingfar Int. and by academic institutions, such as Magdeburg University, Germany and Sahlgrenska University Hospital, Sweden, reaching an annual turnover of approximately [TEXT REMOVED FOR PUBLICATION] ( S5). Since August 2013, total sales of the NTS benchtop imaging system have reached [TEXT REMOVED FOR PUBLICATION], with more than two-thirds of products sold outside the UK. Total sales of the LUMO system since its launch in April 2019, have reached [TEXT REMOVED FOR PUBLICATION] to date and sales of tissue equivalent phantoms have reached [TEXT REMOVED FOR PUBLICATION] since December 2016.

The DOT imaging systems (NTS benchtop system and LUMO) have had a worldwide reach with units being sold in the UK (14 units), North America (8 units), China (6 units) Europe (9 units), Australia (3 units), Gambia (1 unit) and Bangladesh (1 unit). One of Gowerlabs’ Chinese distributors reports that “ The Lumo system has generated a great deal of interest throughout China” ( S6).

Gowerlabs has grown steadily since 2013 and currently employs full-time and part-time personnel equivalent to 5.0 FTE. Since 2013, interns and employees have joined the product development process “ from the first design concepts through to mass manufacturing” ( S7), through which “ invaluable skills and experiences” ( S8) were gained and transferred across the engineering industry as these personnel progressed on from Gowerlabs. A former employee with a consumer-focused design background stated: “ …(At Gowerlabs) I was exposed to several new engineering fields, including flexible printed circuit design, embedded system electronics and near-infrared optics… I have gained many important new skills and experiences from being immersed in the full range of their activities” ( S8).

Both the semi-rigid annuloplasty ring and the sutureless heart valve invented by Professor Burriesci and described above have been on the market through Soringroup (now LivaNova) since 2007 (annuloplasty ring) and 2011 (sutureless heart-valve). Net sales of both products generated an average yearly revenue of approximately USD115,000,000 (12-2019) between 2016 and 2019 in the US, Europe (such as UK and Italy) and the rest of the world. Both devices, marketed by LivaNova, are used globally in areas including Europe (such as UK, Italy and France), the US and Japan, and have collectively been used in over 300 cardiac centres in 34 countries across the world ( S1). The sutureless valve, developed by Professor Burriesci is responsible for annual growth in Livanova sales and occurred despite a significant slowing of the overall market ( S2).

Heart valves for surgical use constituted 11% of net sales for LivaNova between 2014 and 2020. For example, the LivaNova 2017 Year in Review specifies: “ Our Cardiac Surgery business also achieved record sales in 2017, driven by a number of products. […], and our Perceval^® sutureless valve achieved 10 years of clinical use, with sales of Perceval growing double-digits every quarter in 2017” (p3, S2). Similarly, their 2018 Annual Report indicates that, despite the worldwide decline in their heart valve sales, the device developed by Professor Burriesci increased its sales: “ Additionally, increased sales of our Perceval sutureless aortic heart valves were more than offset by a non-recurring sales return reserve of USD3,400,000 recorded during 2018 and continuing global declines in traditional tissue heart valve and mechanical heart valve sales.” ( S2).

Changed practice for cardiac surgeons

Professor Burriesci’s research has improved patient health and benefited heart surgeons. Early clinical results have demonstrated the safety and efficacy of the semi-rigid annuloplasty ring to correct mitral valve regurgitation and confirmed the validity of the technical solutions adopted in the design. Efficiency of the novel design, the preoperative and postoperative mitral annular structures were compared and dynamics performance of different annuloplasty rings, concluding that “ Physio II and RSR could restore the physiologic three-dimensional annular shape, but the annular motion was diminished. Conversely, MEMO could preserve both the anteroposterior movement and folding dynamics, …” ( S3). This was also observed by assessing effects of different types of prosthetic rings on mitral annular dynamics, concluding that “ the annulus motion and annulus shape differed according to the type of prosthetic ring that was used’, and that ‘ Only the Memo 3D and Physio II rings allowed for the remodelling of the annulus, showing both a saddle shape and a normal AP/CC ratio during the systolic phase” ( S4).

A more recent clinical trial carried out on 17 patients using Professor Burriesci’s technology confirmed that “ the Memo 3D ring demonstrates a saddle-shape configuration throughout the cardiac cycle despite its planar shape before implantation, which showed its shape to the physiologic dynamism of the mitral annulus” ( S5). Likewise, the sutureless valve has facilitated minimally invasive procedures, allowing at the same time 60% reduction in the procedure time (from 78 to 30 minutes of mean cross-clamp time), thus improving feasibility of combined procedures and related post-operative outcome ( S6).

Improved health and welfare outcomes

The sutureless valve, which has now been implanted in over 50,000 patients worldwide ( S7), has likewise yielded substantial health benefits and subsequent improvements to the quality of patients’ lives post-operation and returning to ‘normality’ ( S8) of their daily routine. For example, a former patient states: “ I had been suffering from aortic steno insufficiency for the last 7/8 years… I underwent the operation on May 30^th so, 5 and a half months ago. To date I’m satisfied” ( S8). Similarly, another patient said: “ After no more than 20 days since I had left the hospital, I quickly returned to my normal life. Being small, the wound healed very quickly. After a week, I had no pain. I could do everything by myself”. In addition to patient benefit, the sutureless valve is improving clinical practice and reducing costs. A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves published a study that reports: “ The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs” by approximately 25%. ( S9).

In a Press Release from Livanova, dated 4 May 2017 ( S1), both the devices invented by Professor Burriesci are highlighted and declarations from several end users are reported. Rakesh Suri, M.D., D.Phil., Cleveland Clinic and Cleveland Clinic Abu Dhabi said: “ *From this prospective trial, the demonstrated hemodynamics and enhancements in patient quality of life support the practice and use of sutureless valves in patients with severe aortic valve stenosis.*” David Heimansohn, M.D., St. Vincent Heart Center, Indiana, said “ Since I began using the valve over 3 years ago, I have found that the use of Perceval is associated with a shorter procedure and recovery time, which allows patients to return back to their day to-day life more quickly.*” These positive statements are reinforced by a clinician at the University of Brescia Medical School, Italy, who said “ *With Perceval’s technology, cardiac surgeons have a viable solution to standard bioprostheses that can decrease procedure time and reduce post-operative complications. These encouraging results demonstrated that the Perceval valve, when compared to TAVR (*transcatheter aortic valve replacement) , significantly improved patient outcomes for intermediate-risk patients with isolated aortic stenosis”.

In a recent analysis of the decennial experience with the Perceval valve published by Chuvette et al. ( S10) the sutureless valve is highlighted: “ the rapidity of its deployment and its use in narrow spaces”, the fact that “ it alleviates the excess operative risk associated with an annulus enlargement procedure”’ and that the device is “ especially useful in minimally invasive procedures” and in “ double or triple valve surgery, where the use of sutureless technology allows for significant reductions in CPB and cross-clamp times, favourable clinical outcomes, and excellent hemodynamic parameters.”

More recently, in a presentation given in 2019 at the American Association for Thoracic Surgery Meeting, Professor Bart Meuris from Leuven University Hospital (BE) presented data from the longest clinical follow-up for the Perceval valve (12-year clinical experience) ( S7). The results regarding early stroke and mortality “ are better than those reported in both the surgical as the transcatheter arms of large trials comparing TAVR and SAVR in comparable patient cohorts”. The Perceval sutureless valve also “ offers a stable, time-saving and safe surgical result, both in isolated as in combined procedures. We observe promising long-term durability given the current low incidence of SVD* [such as structural valve deterioration] after 11 years of continued clinical use”.

The technologies developed by Professor Burriesci are among preferred surgical treatment options used by leading clinicians. Patients also understand the benefits of the devices. For example, a retired music teacher who underwent valve replacement surgery, was inspired to compose a song following her procedure where she says ‘ I am a proud possessor of a Perceval valve, you know that’s sutureless, very important it’s sutureless. And a five years study don’t you see. So, I better keep going for 5 more years’ ( S8).

UCL research has led to the development and application of analytical tools that enhance vulnerability modelling and are being used by NGOs, finance industries and governments worldwide to inform disaster risk assessments and mitigation plans to protect people and buildings at risk of natural hazards.

• The UCL methodological vulnerability guidelines and associated databases are (i) fundamental components of the Global Earthquake Model (GEM) seismic risk modelling tools, ( ii) used by the financial sector to produce and calibrate the pricing of insurance products for value exceeding EUR 229,000,000,000 in Iceland and Morocco, and ( iii) form the established reference for the World Bank GRADE, which is used to conduct rapid post-disaster situational assessments that inform deployment of USD 1,000,000,000 emergency aid.

• UCL seismic and multi-hazard vulnerability and risk analysis tools are core to the Global Programme for Safer Schools’ GLOSI tool, used to assess and finance the retrofitting of over 57,000 schools in developing countries; and are being used in the Philippines to develop and implement conservation management plans for churches that provide vital shelter during emergencies.

Informing Global Earthquake Model Foundation (GEM) products and training

The UCL Vulnerability Guidelines ( R1, R2) are an integral part of the risk training provided by GEM to increase capacity of local experts in developing countries to assess disaster risk. Since 2014, the training has been delivered to more than 500 participants from 68 countries and the guidelines have been accessed more than 4,000 times via the GEM website portal ( S1). The guidelines were used by GEM to develop the first detailed Seismic Risk Map of the world in December 2018. GEM stated that “ the research from UCL has been particularly relevant on this front…This map has been accessed more than 10,000 times to date, and it is being used by the insurance industry and global organisations such as the United Nations Disaster Risk and Recovery and the World Bank (in particular for Europe)” ( S1). Moreover, UCL’s Vulnerability Database forms the basis of the physical vulnerability database implemented by GEM in their OpenQuake platform ( R5). The latter “ has been accessed more than 5,500 times *between 2018-19. For engineers in less developed countries, this database is the primary source of vulnerability information for their activities. For example, the database was used (by GEM) to provide vulnerability functions to experts in Guatemala for a project regarding the seismic safety of schools. The database has been also used by experts in Nepal for the assessment of damage in the residential building stock.*” As stated by the Seismic Risk Coordinator at GEM ( S1).

Enabling insurance and re-insurance sectors to create new vulnerability and catastrophe models

UCL facilitated the use of its empirical guidelines ( R1) by University of Iceland and the Natural Catastrophe Insurance of Iceland (NTI) to construct new vulnerability models ( S2) that have been used by NTI to update the national risk model for Iceland in 2018 ( S3). The Damage and Risk Analyst at NTI stated “ the new functions have improved our understanding of uncertainty and sensitivity of different parameters. Our seismic risk model is a fundamental part of our risk assessment and we use it in our financial risk management (reinsurance cover, reinsurance pricing) as well as in the general risk management of NTI…for about two years now”. NTI is a government owned agency that reports under the Iceland Ministry of Finance and Economic Affairs and directly uses the risk model to price its catastrophe insurance for earthquakes. The insurance is compulsory for all real estate in Iceland. NTI insures a total of 278,000 buildings with a total value of ISK10,200,000,000 (EUR63,000,000,000) ( S3).

Between 2016 and 2018, the UCL team collaborated with Willis Re, a global reinsurance company, to apply practical hazards risk modelling in the insurance sector. As a result, Willis Re have implemented the UCL vulnerability guidelines ( R1) and database ( R5) to define a new vulnerability model and new catastrophe model for the Middle East and North Africa ( S4,S5). The catastrophe model is used by more than 10 insurers in the region to (a) define their reinsurance capacity and avoid insolvency and (b) price the reinsurance cover in the reinsurance transaction. The Divisional Director at Willis Re states: “The vulnerability database has direct impact on the reinsurance spend of the whole region, where there is no valid alternative to Willis Re catastrophe model in the market to assess earthquake risk. The (…) catastrophe model is a clear differentiator to Willis Re competitors in the region, thus allowing Willis Re [to retain a] large presence in the Middle East and North Africa market …. ‘ The empirical methodology and database [produced by UCL] have been used to assess the risk profile of Morocco and calibrate the parametric cover for the Fonds de Solidarité Contre les événements Catastrophique (FSEC) [the Moroccan National Insurance Monetary Fund Against Natural Hazards] . The cover will allow protecting all uninsured residential buildings, worth approximately USD200,000,000,000, against earthquake events in Morocco, playing a key role in reducing the protection gap in the country” ( S5).

Assisting the insurance and re-insurance sector to use third-party vulnerability functions to evaluate existing catastrophe models

UCL’s vulnerability database and scoring system are extensively used to evaluate catastrophe models from model vendor companies such as Risk Management Solutions and AIR Worldwide ( S5) which can predict significantly different earthquake risk for the same location and assets. Willis Re adopt the UCL database to validate vendor risk models and advise their clients on which models to use to evaluate their reinsurance spending and the cost of reinsurance cover (a market worth approximately USD600,000,000,000 globally). They state: “ the quantity of reinsurance that each insurer buys is directly related to the catastrophe model that proves to be most reliable in Willis Re analysis” ( S5).

At Guy Carpenter, a leading reinsurance intermediary, whose Model Suitability Analysis tool also adopts vulnerability functions that UCL specifically tailored for their system, state that UCL expertise has “ allowed us (Guy Carpenter) to advise our clients on damage functions for a much wider range of building types, (and) enabled us to rapidly up-scale our database of benchmark functions”( S6).

Facilitating damage assessment in post-disaster contexts

GRADE (Global RApid post-disaster Damage Estimate), is a remote, desk-based, rapid damage assessment method deployed on request soon after a disaster. Through collaboration with the World Bank (2014-2018), UCL’s analytical vulnerability guidelines, database and algorithm ( R2, R5) have helped define and calibrate the GRADE methodology ( S7) which allows national governments to rapidly assess damage and develop strategies to support post-disaster recovery and reconstruction. The Senior Disaster Risk Management Specialist at the World Bank stated:”.. .a GRADE assessment following the 2018 Sulawesi Earthquake and Tsunami resulted in the World Bank providing USD1,000,000,000 assistance for Indonesia Natural Disaster Recovery and Preparedness. The value of GRADE’s remote assessments are further apparent during the current COVID crisis, where on-the-ground damage assessments are not possible. This has been demonstrated by the GRADE assessment following the March 2020 earthquake in Zagreb, Croatia.” ( S7).

Enhancing building resilience, globally

From 2017-2020, GLOSI tools, developed by UCL, including dedicated taxonomy, fragility and vulnerability function databases and strengthening measures, have been used in World Bank engagements to assess the seismic performance of national portfolios of school buildings in El Salvador (15,000 school buildings), Dominican Republic (18,000 school buildings), and Kyrgyz Republic (18,000 school buildings) ( S8). In Mexico, the GLOSI taxonomy was used to classify the 6,000 school buildings affected by the September 2017 earthquakes. In 2019, the methodology was successfully used, for the first time, at municipality level in Cali (Colombia) for a portfolio of 300 school facilities. “ The results of these assessments were integrated into an investment planning process …and informed the prioritisation of retrofitting interventions in schools, by maximizing the number of children protected from earthquakes. Over 500,000 school children are benefiting from the ongoing USD 800,000,000 investment programs to intervene vulnerable school buildings” ( S8). In addition, through third party applications, the GLOSI is currently used by Ministries of Education in more than 20 countries worldwide.

Catholic churches in the Philippines act as cultural and social centres and are used as emergency shelters during natural damaging events. Following the destructive earthquake and typhoon of 2013, the Philippines’ Department of Tourism (DoT) commissioned, through the World Bank, an “Assessment Of The Multi-Hazard Vulnerability of Priority Cultural Heritage Structures In The Philippines”, where UCL’s FaMIVE paradigm ( R6) is being applied to at least 28 heritage sites including Spanish colonial period Catholic churches ( S9) and being incorporated into the Guimbal Church Conservation Management Plans. It is also included in training for conservation architects and heritage practitioners in the Philipinnes ( S10).

Hart’s research on orthopaedic implants has identified causes of joint implant failure; led to improvements in joint registry data acquisition and monitoring; and improved patient care by the introduction of an alert system to avoid “NHS never events” in orthopaedic surgery and preventing the use of unsafe generic implants. The improvements in patient care and monitoring are reducing patient anxiety and saving the NHS millions of pounds each year in unnecessary surgical procedures. The evidence provided by Hart’s research was used by the directors of the NHS and the Medicines and Healthcare products Regulatory Agency (MHRA) to provide guidance to over 56,000 patients in the UK.

Orthopaedic implant monitoring

Hart’s implant registry study ( R2) identified significant gaps in registry data and demonstrated the need for data quality improvements in the NJR (largest implant registry in the world with over 60,000 website visits per year). This evidence was used by the medical director of the NJR to implement a programme of registry data quality improvement, resulting in a 12% increase in linkability, where the first implantation is linked to the removal of the implant (212,823 patients), between 2016 and 2019. The UCL-led work has been critical to data users from industry, surgeons, healthcare providers and patients worldwide (including countries such as France, German, Italy, Japan, the USA, Canada, Brazil, Russia, China and many more). The medical director of NJR stated: “ *(this work) has given confidence to hospitals and surgeons that the data used to report the outcomes of their joint replacement procedures is accurate. Similarly, implant manufacturers and regulators have been reassured that the data used to evaluate the performance of different implant designs has been independently validated.*” ( S1)

The group’s size mismatch research ( R1) was “ the first to quantify the prevalence of a mismatch in the sizes of the components used in hip replacement surgery” ( S2), and revealed that such implants with incompatible sizing will release metal into a patient’s blood stream and tissue, leading to failure. The research ( R1) showed this to be a direct cause of failure in every case investigated. This key output from Hart’s work led to a real-time early-warning alert system created by the NJR and Northgate Public Services (NPS) to inform surgeons when a wrongly sized implant had been inserted and enable them to correct the problem before damage is done to the patient. As stated by the Head of Health Registries at NPS, ‘ *This system (has) identified 21 genuine implant mismatches in the first year of implementation.*’ ( S2).

Additionally, as a direct result of the UCL study, NPS retrospectively reviewed the NJR database to identify patients in the UK with potential size incompatibility that were at risk of early implant failure. To date, 172 at-risk patients have been identified ( S3). They are all receiving enhanced clinical follow up through regular blood metal level testing and medical imaging for early signs of high implant wear, at which point revision will be considered. The early detection of these issues prevented unexplained implant failures from occurring, saving the NHS at least GBP1,500,000 in preventable revision surgery.

Hart’s research and expertise has also directly influenced surgeons’ decision in treating patients with mismatched MOM hip replacements. One consultant orthopaedic surgeon said: “ This paper by Alister Hart’s research group at UCL and the RNOH…prompted me to consider mismatch as the cause of unusually high blood metal levels in one of my metal hip patients… (the analysis performed by Alister’s team) confirmed a size mismatch had occurred and, on this basis, I performed revision surgery to remove the components” ( S4).

Removal of unsafe orthopaedic implants from the market

Analysis of generic orthopaedic implants ( R3) showed that truly equivalent generic solutions are not yet possible. This data was used by the UK Government regulator of new implants, Beyond Compliance, to adjust the safety rating that was awarded to this generic design ( S5). This study ( R3) influenced the large-scale debate about the use of generic implants in the UK ( S6), which ultimately saw the manufacturer, Orthimo Limited, being dissolved.

Hart’s program of dual-taper implant work ( R4) showed that these modular stem designs were the single largest risk factor for severe corrosion and implant failure (as opposed to other surgeon, implant and patient factors). These findings were used by the Scientific Committee on Health and Environmental Risks of the European Commission to update their implant safety recommendations, which now advise against this use of dual-taper hips ( S7). These recommendations were welcomed by the UK Medical and Healthcare products Regulatory Agency (MHRA) and since Hart’s publication, modular neck implants are no longer used in the UK due to the knowledge that severe corrosion in these designs has detrimental effects on patients ( S3).

Change in medical practice to avoid unnecessary NHS tests for patients

The findings from the cardiac study ( R5) were used by the head of the NHS to reassure 56,000 patients in the UK who have MOM hips that they were not at an increased risk of heart failure due to their implant ( S8, S9). This study helped address the “ well recognised patient anxiety and increased pressure on the NHS” due to panics over “ higher rate of heart failure”, which is thought to be “ a significant risk to patients, the orthopaedic community and the NHS as a whole” ( S8). Left unaddressed , “the worry was an acute service breakdown due to a crisis that overwhelmed care pathways based on incomplete evidence and fear. This would have meant 56,000 metal hip patients needing to be seen by 2 specialities with a large number of operations having to be redone within as little as 6 months” in the NHS ( S10).

Hart’s MOP hip research ( R6) reassured surgeons and patients with MOP implant designs their implants were safe. This research evidence informed advice given by the British Hip Society (BHS) about the management of MOP patients thereby avoiding unnecessary blood testing and medical imaging on a significant number of patients. ” These guidelines, based on Hart’s research, continue to be the advice from the BHS to surgeons about the management of their MOP patients. This is particularly significant (…) as 27% of the 67,500 primary hip procedures performed in 2018 were of this MOP design ( S11). This led to a saving to the NHS of approximately GBP9,000,000 in 2018 alone by avoiding unnecessary clinical tests.

In 2013, as Hardick completed his doctorate, the nanofibre adsorption technology developed at UCL was sufficiently developed to launch a spin-out company (Puridify), led by Hardick. Puridify, building on research from the UCL team, offered a solution to a variety of manufacturing difficulties for biopharmaceuticals. The collaboration between UCL and Puridify has resulted in a jointly patented new chromatography medium, now commercially available as Fibro PrismA. The impacts of the research have been significant; both its commercial impact on Puridify, and its impact on clients, helping to advance the development of life saving treatments.

Commercial Impact on Puridify

The global market for chromatography resin, a key component of biopharmaceutical manufacture is projected to grow from USD2,100,000,000 (12-2020) in 2019 to USD3,000,000,000 (12-2020) by 2024; a Compound Annual Growth Rate of 7.2%. The market is largely driven by the increasing demand for therapeutic antibodies. The efficiency gains over resin, made possible by Puridify and its Fibro technology platform (commercially available as Fibro PrismA) have huge potential not only of time saved, but also of scalability. The Fibro technology offers faster work rates, and allows a manufacturer to switch more easily between different biopharmaceutical products, potentially making advanced treatments more accessible to low- and middle-income countries.

These efficiency gains make the company extremely attractive to funders and investors. In 2013, the year Puridify was founded, the company won the first Oxbridge Biotech Roundtable (OBR) life-sciences business plan competition. SR One, the venture capital arm of GlaxoSmithKline, provided GBP100,000 and lab space at the Stevenage BioScience Catalyst as a result. This collaboration later led to Puridify winning the 2016 BioProcess International Award for “Best Collaboration” with GlaxoSmithKline to advance industrial evaluation of Puridify’s FibroSelect The company also acquired investment from SR One ( S1), UCLB and Imperial Ventures (GBP850,000 in 2014) ( S2). It received non-diluting funding from Innovate UK (then TSB) for further collaboration with Bracewell at UCL, in recognition of the importance of its research-led work.

This series of grants allowed the company to progress through the technology readiness levels starting with improvements in the material, progressing into device design and finally looking into future application of the technology in viral vector purification (2014-2018). In 2015 Puridify had a Series A funding round successfully raising GBP2,200,000 from SR One, UCLB and Imperial Ventures ( S3). By 2016, Puridify had 14 scientists at their site at Stevenage and 4 postdoctoral researchers working with Professor Bracewell at UCL via Innovate UK funding. The company has also won six Innovate UK Awards since 2013. Bracewell and Hardick were recognised as finalists in the BBSRC Innovator of the year competition in 2015 ( S4).

In 2017, GE Healthcare (the chromatography resin market leader) bought Puridify, recognising its innovation and potential and to gain “ access to exciting technology that could give considerable improvements for some customers in their purification step” ( S5). [TEXT REMOVED FOR PUBLICATION]. This patent, and the technology developed stem directly from research conducted with Bracewell. GE Healthcare maintained the Stevenage site and has grown its 17 staff (at the time of purchase) to 25, and expanded its facilities. In 2018 they opened a pilot scale manufacturing facility for their proprietary nanofibre adsorbent technology on the site ( S6). GE Healthcare was itself purchased by Danaher in 2020 and renamed Cytiva. As Cytiva, the company then launched the nanofiber based adsorbents as a commercial product in spring 2020, while tripling office space and further expanding the workforce. Cytiva is initially focusing on the purification of therapeutic monoclonal antibodies ( S7).

Impact on Clients

Since the commercial release of Fibro PrismA in 2020, customer testimonials of the product have drawn attention to large increases in productivity ( S8). The biologics expression team at AstraZeneca, evaluating fibro against standard chromatography, saw a 6-fold increase in throughput. The purification officer, called the resulting efficiency gains “ substantial… saving two staff one day each per week, so we can focus on more challenging work. It makes a big difference to us.” ( S8).

The Principal Scientist at LifeArc, says, “ The main benefits of Fibro PrismA are speed and efficacy. As an organization that focuses on translation and progressing work from early lab-based findings, Fibro PrismA is helping us to accelerate the research that brings transformative medicines to patients. We have seen an immediate impact on project timelines, including some of our Covid-19 related work” ( S8).

As these testimonies show, the impact is not simply felt in efficiency gains, but the corollary progress in the development of therapies that contribute to wider wellbeing. Fibro lowers the bars to entry for the manufacture of biopharmaceuticals. This technology, and the research that made it possible, is driving further innovation. As Puridify CEO and Bracewell’s former PhD student, says “ We see the continued growth of smaller players in the industry and Fibro is directly intended to be a more attractive option to these players. Following the launch of HiTrap Fibro PrimsA we have seen strong uptake from across the globe and a broad user base which provides a good base for the launch of Fibro products for GMP manufacturing due early in 2021” ( S9).

UCL engineering continues to work on shipping optimisation for defence and commercial use, to improve ships’ design, performance, safety and stability. For example, through novel design shipping concepts, research outputs continue to generate shipping contracts and reduce manufacturing costs. UCL work has also implemented additional safety parameters through ship design software, in turn promoting environmental changes for shipping emissions pathways. As such, work on low carbon technology and waste recovery have reduced environmental impact in the naval industry.

UCL trimaran concept in shipping industry

UCL developed the new concept of a trimaran ship; the research demonstrated advantages of trimaran ships for ferries and naval vessels ( R1-R3). These ships have high speed characteristics due to their slender hulls, large deck areas for carrying cargo and equipment, inherently good performance in waves (over 50% reduction in motion sickness compared to a catamaran), yet providing extended operational profiles compared to monohulls (up to 70% improvement) ( S1). Large ship builders have used UCL research outputs ( R1-R3) to build their vessels. For example, 13 Independence Class trimarans of ​Littoral ​Combat Ships (LCS) have been constructed for the US Navy between 2010-2020 (the latest USS Savannah was launched on 8^th September 2020). Four LCS are currently under construction with a further three on order (S2), with the contract for each vessel worth approximately USD584,000,000 ( S2). UCL research also led Austal USA (a global defence and commercial ship builder) to construct four high speed trimaran ferries for Fred Olsen Cruise Lines, each costing approximately AUD95,000,000 (S2).

Another large high-speed ferry builder, Incat, has used research outputs ( R4) to guide the design of their vessels, to ensure that their vessels are structurally reliable. UCL research has led to changes in the bow shape of Incat vessels to reduce the wave loads and improve passenger comfort (by 25%), leading to structural weight savings of the order of “[TEXT REMOVED FOR PUBLICATION] in large vessels, this reduction in alloy and fabrication costs is worth approximately [TEXT REMOVED FOR PUBLICATION]” (S3).

The DBB approach ( R5) has be used to develop ship designs for organisations and companies such as the UK MoD, BMT, DSTL, UK Shipbuilders & Shiprepairers Association, Canadian Defence Dept, US Navy ONR and Columbian Navy. Many of these studies were in support of governments and industry decision-making on major warship programmes (e.g. UK Type 26 Frigate, Canadian Joint Support Ship programme, UK Offshore Patrol Vessels, new Colombian Frigate). The DBB approach has also provided insights to inform specific design policies (e,g, topside design (NDP), personnel movement beyond just escape (UK DNA), design for survivability (DSTL), AXV impact on ship design (Babcock, BAES, NDP) and distributed systems (USNavy-ONR).

Improved safety for naval architecture design

UCL research into safety approaches ( R6, R7) has led to changes of practice in global industry leaders. The outcomes from UCL research associated with quantitative risk assessment and management against fires and explosions have been transferred to the world’s leading construction companies of offshore installations, namely Hyundai Heavy Industries (HHI) and Daewoo Shipbuilding and Marine Engineering (DSME). They partnered in the Joint Industry Projects and are using research outputs ( R6, R7) for their safety engineering of topside modules of FPSOs, for safer structures against extreme conditions and accidents. The outcomes have been used to achieve safer structures with improved tolerances against such extreme conditions and accidents. HHI state (S4) that using research outcomes has “ provided the impacts associated with not only economical benefits by lowering engineering costs but also safer structural designs by enhancing the safety and production quality. Depending on the complexity and size of structures, the benefits have been achieved up to 5 million USD per vessel”.

UCL research outputs on ULS ( R5, R6) have been directly implemented into MAESTRO software, for design optimisation. Specifically, into ALPS/ULSAP and ALPS/HULL computation modules, to provide computational efficiency and greater accuracy for buckling and ultimate strength for plates and stiffened panels, and hull girder collapse for ships. These outputs have been successfully integrated into MAESTRO to improve ship structural design. MAESTRO Marine LLC state “ The combined capabilities of MAESTRO with ALPS/ULSAP has ensured that MAESTRO has an advanced capability for structural panel-level limit-state analysis. Together the ALPS computational tools enable large scale optimization of sophisticated warships and advanced commercial vessels…and in supporting effective in-service structural engineering for ships through their life cycles.” (S5).

There are 90 active ALPS users are in 23 countries, including Navy (eg US, Japan, Australia, Spain, Brazil, Columbia, South Korea), Coast Guard (eg USCG) and engineering companies (eg Navantia, Ingles, BIW, DSTO, SeaxeMers, Serco). User SpaarnWater have used Maestro for structural evaluation of maritime objects for over a decade (S6). In a testimonial SpaarnWater state “ MAESTRO is an excellent tool to perform a structural analysis of a complete maritime structure already in an early stage of the design process supporting the naval architect in his design decisions. SpaarnWater will continue to use MAESTRO as its main tool in structural design and analysis of maritime objects.”

Qinetiq, another user of UCL computational models through Paramarine®, state the tool is " an integrated naval architectural design and analysis tool set (enabling) seamless collaboration between global teams", including "over 200 organisations worldwide" and used on " designs from aircraft carriers and submarines to commercial ships and megayachts" (S7).

Reducing the environmental Impact of shipping

Through stakeholders’ collaborations, UCL research outputs have also helped reduce the environmental impact of the shipping industry by providing tools that support development of low carbon technology and better waste recovery. The improved technical models for ship designs, technology developments, and low carbon technology ( R8) were amalgamated into GLOTRAM, UCL Energy Institute’s (UCL-EI) techno-social-economic model of the global shipping industry. GLOTRAM influenced the shipping industry through changes in transport demand, macroeconomics (such as fuel, carbon price and newbuild price inflation), and the availability of technology and regulation (such as regulations on greenhouse gases and other emissions to air).

As such, the success of UCL-EI collaboration led to the allocation of the 3rd IMO GHG study, commissioned by the UN agency International Maritime Organisation (IMO) estimating the total GHG emissions from shipping; and has become a key reference in industry and policy debates. This work was submitted in its entirety to the IMO by the governments of Belgium, Denmark, France, Germany, Marshall Islands, Netherlands, Solomon Islands, Tonga, Tuvalu in the 71^st session UN IMO Marine Environment Protection Committee (MEPC), at a critical point in the negotiation leading up to the climate deal (S8). Not only has the MEPC become the key reference for future shipping emissions pathways aligned with the Paris Agreement temperature goals (S9), but also provides technical background for specifying key commitments in the UK government’s breakthrough policy Clean Maritime Plan, as well as to achieve UK government objectives on reaching net-zero by 2050.

Through the UCL-Bowman Power collaboration on marine engines, UCL research outputs on waste recovery led to the development of a new marine waste heat recovery unit. Independent tests at Cranfield University showed that this new system “ recovers 30% of waste heat thereby improving efficiency in the region of 5%” (S10). It is now being readied for commercial and naval marine markets with ongoing discussions with shipping company Stena.

The rheological model developed at UCL and implemented in CFD simulations ( R1, R5,R6) has significantly enhanced product and process knowledge of the mixing of complex fluids. This rheological model was implemented by [TEXT REMOVED FOR PUBLICATION] ( S1,S2) and, according to [TEXT REMOVED FOR PUBLICATION] Annual Report 2019: “ recommended most often for sensitivity in 70% of markets” ( S1). [TEXT REMOVED FOR PUBLICATION]. Professor Angeli’s research contributes to [TEXT REMOVED FOR PUBLICATION] ( S3). The research also contributes to [TEXT REMOVED FOR PUBLICATION].

Professor Angeli shared progress of her underpinning research ( R1-R6) with [TEXT REMOVED FOR PUBLICATION] via several routes. These include direct meetings between Professor Angeli and her group and the company, emails, visits, round table discussions and presentations to the company, participation of research students in the [TEXT REMOVED FOR PUBLICATION], PhD annual conference and secondments of PhD students to the company. Within the company the information has been disseminated from R&D into the production sites through points of contact and trials. This has led to optimised production time and processing and personal development for researchers.

UCL’s novel modelling approach to optimise production time and manufacturing processes

UCL’s viscosity model and supporting CFD studies were used to reduce production time and optimise the process. The viscosity of the gel formulation, which influences mixing, is very sensitive to temperature. Previously the temperature range was used as one control  of the gelation. The knowledge of the detailed correlation between temperature and viscosity ( R1), enabled the operation of the mixing unit over a tighter temperature window that reduced the batch cycle time. Through reduction of batch cycle times, Professor Angeli’s work therefore helps respond to consumers’ higher demand to address tooth-sensitivity with access to products in the UK and worldwide such as Romania, Saudi Arabia, the USA and South America to name a few ( S4,S5).

Specifically, the optimised temperature range for core gel premix led to a reduction of the batch cycle time of [TEXT REMOVED FOR PUBLICATION] . UCL’s technique therefore [TEXT REMOVED FOR PUBLICATION] ( S2). As a result of better operation and optimal process control following Professor Angeli’s and Dr Mazzei’s CFD studies contributing to [TEXT REMOVED FOR PUBLICATION] was able to meet consumers demand through over the counter products and [TEXT REMOVED FOR PUBLICATION]

UCL’s rheology model was also used as a fast-technical assessment tool for new non-aqueous formulations. It enabled risk quantification when working in near critical conditions, thus reducing the need of costly pilot scale trials. This has led to timing reduction of [TEXT REMOVED FOR PUBLICATION] ( S2). The detailed rheological studies from UCL and the effect of temperature have revealed the kinetics and times involved in the gelation process and led to alternative processing routes where mixing of low viscosity materials at room temperature precedes the gelation ( R4).

This novel approach ensures faster processing times, better mixing and reduced heat requirements; in turn [TEXT REMOVED FOR PUBLICATION] ( S2). A recent survey conducted by the UK government in 2020 showed that the number of users for the [TEXT REMOVED FOR PUBLICATION] range increased by 9% in the UK (from 2018 to 2019) ( S6); this shows that Professor Angeli’s modelling continues to facilitate ease of toothpaste productivity and meeting consumers increased demand to address their oral health. The ability to meet consumers demand through innovation is no surprise in oral healthcare, since “ Customers seek innovative, multifunctional oral care products that can deliver results and help maintain oral hygiene” ( S7).

[TEXT REMOVED FOR PUBLICATION]

Panagiota’s work on complex fluids has supported market growth for [TEXT REMOVED FOR PUBLICATION] . Her work has contributed to a brand worth GBP270,000,000 in book value and contributing to the 7% growth of oral health sales ( S1). Professor Angeli’s work also initiates energy savings, in alignment with [TEXT REMOVED FOR PUBLICATION] current commitment of “t ackling climate change…reducing its carbon footprint in line with the Paris Agreement” ( S1).

Substantial training and personal development for researchers

The UCL research team have contributed to training company stakeholders and also the next generation of scientists. Through the [TEXT REMOVED FOR PUBLICATION] -UCL collaboration, PhD students received industrial preparedness through [TEXT REMOVED FOR PUBLICATION] leadership and experts in the field ( S2). They spent time working on the company site, where they received training on safety and industrial practice. A former PhD student seconded to [TEXT REMOVED FOR PUBLICATION] for 6 months as a Product Development Engineer, is currently employed as a Product Development Engineer at Repsol, Spain supporting development of motorcycle engine oils, working with complex viscous fluids and using “ all skilled acquired (…) at UCL and at [TEXT REMOVED FOR PUBLICATION] ” ( S8) . As both lubricants and toothpastes are complex viscous fluids, the Product Development Engineer at Repsol, is currently implenting skills gained through the UCL-[TEXT REMOVED FOR PUBLICATION] collaboration solving motorcycle engine oil problems.

Similarly, one post-doctoral research assistant (PDRA) has now progressed to an academic post focusing on CFD research and teaching, while another PDRA has moved onto data analytics. The UCL-[TEXT REMOVED FOR PUBLICATION] partnership is therefore, promoting transferrable technical skills (such as communicating technical information to versatile audience and senior company leads) in industry within a short timeframe.

Application of mathematical modelling in industry

The methodological approach developed which combines the detailed characterisation of complex mixtures and the subsequent development of models ( R6), have attracted further collaborations. As an example, Johnson Matthey Plc (JM), a global leader in sustainable technologies, is currently collaborating with Professor Angeli looking at continuous processes involving complex multiphase mixtures for separations in the pharmaceuticals industry. A Principal Scientist for Separation Technologies and Process Chemistry at JM , states that ‘ JM was very attracted to working with Professor P. Angeli at UCL for her expertise in fundamental chemical engineering science. In particular, her on-going in-depth work on complex multiphase flows, advanced experimental capabilities, mathematical modelling, and the characterisation of mixture properties’ ( S9). In January 2020, this led to JM funding an EPSRC industrial CASE PhD award of GBP39,132 over four years. As of December 2020, the UCL-JM collaboration has already provided new understanding on novel design and optimisation for extraction flow systems for JM, which they continue to pursue.

In a “ remarkable collaboration of medicine” (Lord Agnew ( S1)), the UCL-Ventura team brought together engineers at UCL and Mercedes AMG High Performance Powertrains (HPP) with critical care consultants at UCLH – one of the largest UK teaching hospitals. Against the national backdrop of the UK Ventilator Challenge and predicted need for up to 30,000 mechanical ventilators, the UCL engineers and UCLH critical care specialists, recognised that CPAP devices that are well-established as a “halfway house” between an oxygen mask and invasive mechanical ventilation and can be offered outside ICUs could help, but there was an acute national shortage of CPAP devices available.

Based on the experiences of China and Italy, CPAP had the potential to alleviate around 50% of patients from progressing to mechanical ventilation, improving patient outcomes as well as enabling vital critical care resource to be reserved for those patients who needed it the most. Computational modelling and engineering design were pivotal components to the innovation pipeline, in turn enabling national and international collaborations with engineering companies, international governments and not-for-profit organisations, to address global healthcare needs.

The UCL-Ventura team first met on 17 March 2020. Within 100 hours, they had designed and manufactured the first reusable UCL-Ventura prototypes and began testing them on the wards at UCLH. Within 10 days (27 March), the Mark I UCL-Ventura received regulatory approvals for use as part of the emergency COVID-19 response from the MHRA, with the Mark II device following days later. By 15 April 2020, Mercedes HPP had manufactured 10,000 devices, with 125 NHS hospitals supplied by December 2020. On 5 April, the blueprints of the UCL-Ventura were released at zero cost, downloaded over 1900 times across 105 countries, with extensive manufacture and hospital deployment by around 20 teams internationally by December 2020.

From computational modelling to regulatory approvals and mass-manufacture

Professors Shipley and Baker’s expertise in computational modelling, bench testing, engineering design and medical devices ( R1-R3) was pivotal in the rapid design and deployment of the UCL-Ventura. This expertise enabled the reverse-engineering of the Philips WhisperFlow, with prototypes ready for testing at UCLH within 100 hours. Simulation work on the flow profiles generated in the flow generator and accompanying breathing circuits were essential for their redesign to form the Mark II UCL-Ventura device, approved by the MHRA within 13 days of the first meeting. This simulation and design work enabled a 70% reduction in oxygen utilisation, essential for deployment in the NHS at a time of unprecedented demand on hospital oxygen supplies ( S2). Ultimately, five MHRA approvals were obtained (Mark I and Mark II CPAP, 2 oxygen analysers, 1 CPAP hood), all progressing to mass manufacture and distribution to NHS hospitals. The manufacturing excellence provided through Mercedes AMG HPP was pivotal; machines that would normally produce F1 components were used for manufacturing reusable CPAP devices to meet the global demand for the device.

Supporting the National Health Service through industrial partnerships

In April 2020, the Department of Health and Social Care ordered 10,000 CPAP devices ( S3), completed within “ 15 days from the confirmation of order’” (Managing Director of Motorsports, Formula 1) ( S3), with UCL leading on the [TEXT REMOVED FOR PUBLICATION]. Production was conducted at the Brixworth Formula 1 Northamptonshire factory at a maximum rate of up 1,000 devices a day ( S4). Partnering with automotive logistics company G-TEM, CPAP kits were distributed across more than 125 NHS hospitals in England, the devolved nations, crown dependencies and overseas territories. The General Secretary of the European Society of Intensive Care Medicine highlights that CPAPs enabled large UK hospitals to offer “ life-saving treatments to patients in a timely fashion…take critically ill patients from local trusts”, and “ prevented many patients from being exposed to the risks of sedation and mechanical ventilation” ( S2).

Not only has the UCL team enabled “ rapid mass production.. to be distributed speedily’ across many UK hospitals (Chief Executive at UCLH), but also ‘ the device has been a game changer in the management of a very large number of COVID-19 patients with respiratory insufficiency…in the United Kingdom” ( S2). During the second wave response for Covid-19, 60 devices were provided to both University Hospital Lewisham and Queen Elizabeth Hospital Woolwich. According to the Consultant in Intensive Care Medicine at University Hospital Lewisham, “ within 2 or 3 minutes of consumables being assembled’, patients could benefit from the UCL innovation and there were “ no reported patient clinical incidents during the time these devices were used” ( S2). The availability of the UCL-Ventura CPAPs contributed to “ reduction in secondary harm caused by mechanical ventilation and associated organ dysfunction’ by reducing rate of invasive mechanical ventilation by over 50%” ( S2).

There has been a marked shift in clinical practice across the UK since the beginning of the pandemic with far greater use of CPAP as hospitals recognised this was both an effective strategy and, crucially, spared stretched intensive care resources for the most critically ill. From March to June 2020, use of mechanical ventilation fell by 26% for equally sick patients, intensive care stay has halved for survivors, and mortality fallen by a quarter ( S5).

International collaborations to improve healthcare systems and patients’ outcomes

By mid-April 2020, to contribute to the global humanitarian effort, the consortium released blueprints of the full design and manufacturing instructions at zero-cost to support in-country manufacture. As of December 2020, these designs have been requested over 3440 times and access has been given to over 1900 teams from 105 countries around the world ( S6). Over 20 countries (including India, Mexico, Pakistan, Peru, Paraguay and South Africa) have succeeded in extensive local manufacture and hospital deployment of the UCL device.

Professor Shipley and the team worked with in-country teams, particularly through the Department of International Trade and Foreign, Commonwealth and Development Office to provide support to local teams spanning technical and manufacture, supply chains, regulation (working with the MHRA), and clinical guidance. By the end of December 2020, over 400 devices were manufactured in Peru, in use in more than 40 hospitals across the country, with the demand for invasive ventilators decreasing by around 50% ( S7). Locally manufactured devices are also helping patients in countries including India, South Africa, Colombia and Mexico. Some of the 500 devices manufactured in Pakistan have been donated to neighbouring countries – including 50 to Tajikistan – as part of a humanitarian effort ( S7). Two leading Australian automotive firms, Walkinshaw Automotive Group and Premcar partnered together to assist Australian healthcare system by manufacturing UCL CPAPs to local hospitals ( S7). Mercedes-Benz South Africa have donated 500 UCL-Ventura devices to 90 government hospitals in the Eastern Cape province ( S7).

Following extensive engagements with government departments, Professor Shipley and her team partnered with the International Medical Education Trust (IMET2000) to deliver CPAPs for use in Palestine (5 hospitals) and Uganda (2 hospitals) ( S7). Working on a non-profit basis, the UCL team has fundraised to cover basic manufacturing and supply costs of the CPAP kits for those most in need globally, for example raising over GBP25,000 to send more UCL-Venturas to Palestine.

Professor Shipley and the team continue to assist with knowledge transfer by providing technical and manufacturing support to in-country teams, particularly on the mechanics and engineering design of the UCL-Ventura CPAPs, and their operation in diverse clinical settings. The UCL team have delivered extensive knowledge transfer activities, for example clinical training programmes (to over 600 doctors and nurses in Palestine, through IMET2000 and Medical Aid for the Palestinians) ( S7), translated learning videos, online webinars and Q&A advice. Such activities have helped health workers to understand the engineering concept and functionality of such a “ simple, yet complex medical tool” (health worker at Hugo Chavez Hospital, Palestine) ( S8). YouTube videos on the operation of the UCL-Ventura alone have received over 58,000 views ( S9). The UCL team has received widespread global coverage through the likes of BBC News, Times, Al Jazeera, Sky Sports, La Vanguardia (Spain) ( S4).

In recognition of the efforts, the team received the Royal Academy of Engineering’s President’s Special Award for Pandemic Services and engineering co-lead Professor Tim Baker was awarded an MBE for services to healthcare in the UK and abroad. The team is working with policymakers to maximise the learnings from the project and was featured in the government’s report on The 4^th Industrial Revolution Response to COVID-19, which commends the relationship between UCL Mechanical Engineering and Mercedes AMG HPP for providing “ unprecedented manufacturing capability, whilst maintaining high precision and an ability to respond at pace” ( S10).

Since 2013, Zinwave Ltd has developed global activities. Through the UCL patent and subsequent development ( R4, R5, R6), Zinwave wireless over fibre systems continue to be deployed. Its unique selling point, namely wideband radio-over-fibre distribution of radio signals over a DAS network, uses research carried out in the FRIDAY ( R2) and subsequent RAIS projects. The Zinwave DAS is a three-stage system for in-building cellular and wireless services, constituting a primary hub, secondary hubs, and remote units. It uses multimode or single-mode fibre cable for connectivity.

The technology features true wideband capabilities allowing simultaneous support for any wireless standard including 2G, 3G, 4G, LTE, PMR/LMR, DVB-H, TETRA, Wi-Fi, WiMAX and RFID. Full management control over this spectrum allows new services to be added on-demand without deploying additional system components. The technology can be configured in a single, dual star or mixed architecture to meet exact service needs. The advantage to the customer is that a single distribution system can distribute multiple wireless services operating with different protocols and at different frequencies. A single system can carry private VHF radio, public safety radio, such as TETRA, 2G cellular services at 900MHz and 1,800MHz and 3G/4G services at 800MHz, 900MHz, 1,400MHz, 1,800MHz, 2,100MHz, 2,300MHz and 2,600MHz from multiple operators.

Zinwave’s global reach

Zinwave has introduced wideband distributed antenna systems to the global marketplace, with systems deployed in Europe, the USA, the Middle East, Australia and China. Since mid-2018, the company has been registered in England and Wales, with its corporate headquarters in Dallas, Texas, technology development in Cambridge, England and offices on the East and West Coasts of the US, in Macau and in Australia. This has created a need to open additional facilities to support the company's world-wide customer base and “ anticipate strong market demand” for the company's solutions, states Zinwave President and CEO ( S1). Its systems provide wideband wireless coverage in shopping malls, auditoria, office buildings, casinos, convention centres, hospitals and airports, in the US, European countries (such as Iceland and the Netherlands), the Middle East and the Asia-Pacific region (such as Jordan and Australia respectively).Through Zinwave Ltd, Professor Seeds' research underpins the Zinwave 3000 System, the Zinwave DAS solution and the Zinwave 5000 UNItivity solution. These products have provided communications solutions for diverse applications.

Zinwave’s technology deployed in healthcare facilities

Using the technologies developed by Professor Seeds and his team ( R1-R6), Zinwave’s existing partnerships with over 40 specialist in-building system integrators continues and since 2013 has extended its reach into both commercial and public safety markets. Testimonies from these partners attest to the cost-effectiveness, ease of use and flexibility of the Zinwave DAS for its customers. For example, following patient and visitor concerns over mobile phone connection problems, the Broomfield Hospital Trust, with a space reaching 43,000sqm ( S2), identified Zinwave DAS as the most suitable and cost-effective solution to signalling problem ( S2, S3).

The IT Operations Manager at Mid Essex Hospital NHS Trust stated: “ The key decision in us moving forward with Zinwave as a solution was the vendor agnostic operator approach...we have high praise for the smoothness of the installation” ( S3), which was completed within 8 weeks of approval. The conventional approach would require the installation of dedicated narrowband equipment for each and every different wireless standard, which is less flexible, more expensive and more complex to maintain ( S2). In addition, Erasmus Medical Centre and Martini Hospitals (Rotterdam and Groningen, Netherlands, with total areas of 365,000sqm and 134,000sqm respectively) have also deployed Zinwave technology ( S2).

Zinwave solutions deployed among public venues

Using the technologies developed by Professor Seeds and his team ( R1-R6), Zinwave has provided solutions for the 9-11 Memorial Museum, New York City (10219sqm), with a reach of 3,000,000 visitors annually, Queen Alia international airport in Jordan, serving over 6,000,000 passengers annually and with building facilities spanning a total area of 19,000,000sqm ( S2). Zinwave performance enabled Queen Alia Airport to overcome several safety and performance concerns and secured the competitive commercial TETRA licence for the 350-360 MHz band. Zinwave solutions continue to be adopted at the Jakarta International Airport (2,458,000sqm); and the Westfield retail complex in Sydney, Australia (88,000sqm).

Zinwave’s products deployed in commercial real estate and enterprise

In 2017 the Zinwave DAS solution, based upon Professor Seeds' research ( R1-R6) was deployed to eliminate wireless coverage and capacity issues at Sky’s new headquarters in Osterley West London, UK (with a combined total area of approximately 46,000sqm) ( S4). The Sky campus in West London had recently undergone an extensive redevelopment, consolidating the company's operations. With multiple floors and the use of dense materials, mobile signal coverage was heavily affected, which led Sky to turn to experienced Systems Integrator Herbert, who recommended the globally proven Zinwave UNItivity solution, which ensures that wireless communications (mobile signal, public safety and IP access services) are always available. The Planning & Delivery Manager (for Network Implementation) at Sky said; “ Sky is very forward thinking and technically capable, and had the foresight to install single operator DAS in our existing buildings on campus, but when it came to our new Sky Central building, we wanted multi-operator coverage to cope with user volumes and multiple Mobile Network Operators throughout this much larger building… Zinwave UNItivity met the desired criteria, with Herbert pulling out all the stops with the project scoping, implementation and in-building integration in the timescales required” ( S4).

As such , the Marketing Director at Herbert states that “the implementation of innovative turn-key solutions such as the Zinwave UNItivity product … ultimately keeps their business at the forefront” [ S4]. Zinwave’s UNItivity system was also selected to provide a sustainable and in-building future-proof wireless user experience at Imperial Pacific Resort Hotel in Saipan, a 14-storey building with a total area of 140,000sqm. According to the CEO of DC Systems, not only were they “ impressed with the UNItivity system’s ease of installation” at the resort ( S5), but it now delivers “ the kind of seamless user experience the Imperial Pacific Resort Hotel had hoped for “ ( S2) for their employees, guests and visitors.

Zinwave DAS solutions, again based on Professor Seeds' research [R1-R6], have also been adopted for applications as diverse as a Garmin data centre in New Jersey, Convention Centre Dublin (4,500sqm exhibition space), The Pepsi Center, Denver CO (roughly 62,700sqm), Norwegian Cruise Line Terminal, PortMiami, FL and the Harpa Concert Hall and Conference Centre, Reykjavik (28,000sqm) ( S2).

Finally, as a result of Professor Seeds' sustained research and stakeholder collaborations, Zinwave was acquired by McWane Inc. in 2014 and annual revenues have risen from GBP3,572,000 in 2013 to over GBP10,000,000 in 2019 ( S6).