Impact case study database

The impact derived from the QT Hub in Sensors and Timing is on commerce and the economy, specifically influencing national public funding priorities and commercial strategic decisions, investment and product pipeline in quantum technology and securing its future in the UK. The QT Hub has established an industrial ecosystem in second generation QT, principally in ultra-precise clocks and gravity sensors. The ecosystem consists of component suppliers, system integrators and end-users, with application in numerous sectors from defence and healthcare to civil engineering. The Hub has over 110 projects, valued at approximately £120M, and 17 patent applications [E1].

Influence on national research strategy, the agenda of Dstl and public funding

We led the MOD executive agency Dstl to include applications in next generation sensing technologies in its research strategy through our work on compact and robust ultra-cold atoms systems [KF1, KF2] and through knowledge transfer as a result of KF3. In particular, gravity sensors [KF3] provided new deployable capabilities for the MOD and ultra-precise clocks [KF1, KF2] allowed access to secure time, which underpins all national and economic security. Both also contribute to novel resilient navigation and mapping systems, which are key priorities for the MOD. Dstl confirmed that “Before [Birmingham’s] work, we had not been able to identify how to engineer systems which will provide the capabilities critically required in the future” [E2].

Our work led to a change in Dstl’s funding strategy and the largest academic R&D investment since its creation in 2001 [E2], thus impacting the development of new technologies. In 2014, Dstl invested [text removed for publication] for QT in Bongs’ research to develop 2 demonstrators (a transportable gravity imaging system and an optical lattice atomic clock). Moreover, Birmingham’s research [KF3] directly contributed to gravity sensors being included in the key Dstl UK QT Landscape document (2014), ensuring that sustained investment in QT has become an industry priority [E3]. Dstl’s Senior Research Fellow in Quantum Technologies stated that “Dstl greatly admires [Birmingham’s] outstanding success in delivering a major part of the UK National Quantum Technology Programme (UKNQTP) [. . .] Within MOD Centre, [Birmingham’s] success in developing new technologies for Dstl and the UKNQTP has attracted notice at the highest levels in Defence Science and Technology (DST, which sets strategy for future MOD investment in technology), the Front Line Commands (FLCs) and UK Strategic Command and Defence Equipment & Support” [E2].

In turn, this collaboration led Dstl to commence building internal capability to carry out R&D for militarily deployable sensing systems. The importance of our contribution to this capacity building is evidenced by the recruitment, in 2020, of 2 permanent members of staff to Dstl from the Birmingham team whose specialist roles draw on our research to enable technology translation. Dstl confirms the pivotal role of Birmingham’s researchers, stating that “The continued collaboration will accelerate knowledge and technology translation from [Birmingham’s] team into Dstl and increase Dstl’s and the MOD’s understanding of the potential of these emerging ‘quantum 2.0’ technologies” [E2].

Influence on strategic decisions, investment and product pipeline in QT

We created the confidence for companies to invest and change their research strategies, through our demonstration of small, light, low-power, and yet robust, quantum sensors and ultra-precise clocks [KF2, KF3]. This was further catalysed by the significant and agenda-setting investment by Dstl. There was no commercial activity in QT sensors and clocks before our findings, but over 30 companies have now invested £25M, including £7M towards 31 Innovate UK-funded projects (with a total value £26M), working collaboratively with the QT hub to create new commercial products [E4]. Highlights include:

• Significant industrial investment exceeding [text removed for publication] from international companies, including

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• [text removed for publication] new products, including a sequencer for quantum sensors, quantum sensor vacuum systems, the development of additively manufactured magnetic shields, a miniature atomic clock, a quantum gravimeter and a gravity gradiometer;

• 3 international companies ([text removed for publication]) setting up offices in the West Midlands and contributing to the local economy;

• [text removed for publication] [E5].

From the vast number of industrial collaborations with Birmingham, 4 examples are provided to illustrate the significance of commercialising quantum technology.

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Stimulating the development of the QT sector and securing its future

Our leadership in QT has materially contributed to the success of the QT sector as a whole, setting the agenda for government and industry. In 2019, the Treasury announced £94M of government funding to extend the QT Hubs, thus providing increased security and expansion of QT commercialisation. This would not have been possible without the significant contribution of the 4 national QT Hubs and Bongs and the other Hub directors providing evidence before the House of Commons Science and Technology Select Committee [E12]. This work has demonstrated the development potential of the QT sector and the viable application of QT research in critical national and economic security [E13].

We have improved the confidence of school teachers to teach physics and provided them with tools to do so, and we have improved the perception of STEM subjects amongst schoolchildren (primary and secondary) and made these subjects more accessible. We have enabled under-represented cohorts to feel they can continue with STEM subjects in higher education, and we have enhanced public understanding of physics through collaborations with artists to facilitate improved communication of science.

The way school teachers deliver physics curricula and syllabi has changed as a result of them participating in our training programmes (Lazzeroni), which are underpinned by lessons and resources based our Particle Physics research [R1, R2]. Specifically:

Over 300 primary schoolteachers from the UK, Italy and Greece delivered our lessons and resources in their schools after we had trained them [A, E]. This exposed children to cutting-edge physics research for the first time and reached around 5,000 UK children at more than 10% of primary schools in the West Midlands. Two international pilots reached around 550 children in Italy and 750 in Greece [A, E]. It was our dissemination of best practice in the educational literature [H] that led to the Italian programme, in which we trained teachers from 20 schools in collaboration with the Italian National Institute for Physics and Nuclear Research (INFN) [A, E]. The programme is in the process of being formally adopted (from 2021/22) as part of the teachers’ training programme at the University of Turin [E].

A key change which resulted from our programme was that teachers are more confident to deliver physics in lessons. A Head Teacher in Italy said: “one of the key aspects of the program, namely the training of teachers by scientists, has been crucial in enabling the teachers to acquire a confident knowledge of the subjects” [E]. As a proxy indicator, of the 50 UK and Greek teachers we trained through the CERN pilot project Playing with Protons [A, G] which includes our resources, 100% said they had become more creative in their teaching methods and 80% confirmed that their confidence to deliver lessons had increased [C].

Our programmes have also changed how educators approach their everyday practice. Of 900 UK secondary schoolteachers who undertook our training, around half of those surveyed said there would be visible changes in their daily teaching delivery, and 78% said they would use our resources [C]. This equates to changing practice at one in ten of UK secondary schools, and the majority of those in the West Midlands.

Perceptions of science have been positively changed for those cohorts of primary and secondary schoolchildren in the UK and Italy who engaged in our programmes. Specifically:

Understanding, attitude and interest towards physics was promoted amongst schoolchildren though our World of Particles, Particle Physics through Visual Art and Particle Dance programmes, which used activities based around play, drawing and sculpture to teach Particle Physics and our latest results at CERN [R1, R2]. This is bridging the gap between making science physically accessible, and understandable and relevant, which is essential to capturing students’ interest during their education. These engagements improved levels of understanding of physics, shown by the fact that of 595 primary schoolchildren at 17 UK schools who participated in World of Particles, 90% reported that they had spoken to their family about what they had learnt and 95% were able to correctly recall information taught on the programme over a month later [C]. World of Particles was developed with the Ogden Trust, supported by a prestigious STFC Public Engagement Fellowship (Lazzeroni). This impact was recognised through the award of the 2019 Institute of Physics Lise Meitner Medal and Prize to Lazzeroni for “her exceptional innovation and leadership in making contemporary Particle Physics accessible to a large and diverse audience.”

The programmes have made physics a more accessible subject [H], with more than three quarters of the 200 children who took part in the Particle Physics through Visual Art and Particle Dance workshops confirming this. Nikolopoulos won the inaugural ERC Public Engagement with Research Award (2020) for this “impact on people that are not the regular audience for frontier science.” Children’s interest in science has also improved through their participation in the programme, with 93% of the 595 UK children and 75% of the 550 Italian children who took part reporting that they were more interested in science than before [A, C, E].

We have made studying STEM subjects at university and pursuing a career in science more attractive for secondary school students, especially for women and for those from disadvantaged groups. We did this through our student-led research programme [A, C, E, G] where schoolchildren used particle detectors [R1, R2] from the European HiSPARC Project to perform their own research. We engaged 1,650 children in 13 regional schools. 90% of the 2015 cohort who were surveyed in detail decided to pursue science in Higher Education compared to fewer than 10% considering this before [C, E]. Half of the schools are from deprived areas, with a quarter in the most deprived decile [A]. Ensuring that students from these backgrounds, who tend to lack science capital, have opportunities to engage further in this area is important in terms of its contribution to diversification in STEM subjects. Around half of this cohort were female students, who are also less likely to study a STEM subject at university or enter a STEM career than their male counterparts; enhancing their understanding and enthusiasm for science subjects is vital to ensuring that the field is more inclusive. To give an example, one HiSPARC year-group from Bordesley Green Girls School in an under-privileged area of Birmingham presented their work at a Royal Society Summer Exhibition. Their teacher said “some were mistaken for undergraduates and offered jobs!” [E]. This change in attitudes was also seen among those on the Particle Physics through Visual Art workshops, of which 33% reported being more likely to study physics at university than they were before the activity [H].

New ways of thinking among artists have been generated through our co-production of exhibitions, performances and events [A, E]. Working with artists who employ sound, dance, opera, photography, film and technology, our PHYART@UoB programme produced new forms of artistic expression — inspired by and incorporating all areas of the underpinning research (Chaplin [lead], Triaud, Nikolopoulos and Freise) [R1–R6] — and ultimately enabled the artists to reach audiences in new settings [A, C]. One artist said that working together had “fostered new relationships and platforms to share the work”, while another stated that “sharing ideas with direct feedback and applying them directly afterwards allowed for richer and creative compositions” [E]. Key examples of this extended audience reach are the presence of our collaborative work at science museums (Thinktank, Birmingham; We The Curious, Bristol) and science festivals (e.g. Oxford IF) with a combined audience of almost 14,000 [A] who otherwise may not have engaged with this novel interconnection of art and science.

These collaborations, which benefit both science and the arts, have been identified as exemplars of best practice in the National Coordinating Centre for Public Engagement’s (NCCPE) consultation and report on how researchers and artists can work together to engage the public with research [G]; and in the Arts and Humanities Research Council (AHRC) Cultural Value Project, which looked at why the arts and culture matter and how we capture the effects that they have [G]. That this has enhanced creativity within the STEM field is evident through Wire music magazine’s review of our work with artist Devine, which stated it “reminds you that it’s still possible to factor in human imagination and physical presence into our understanding of the universe, something that’s missing from so many other big data projects” [F].

Public audiences’ perceptions of physics have changed through their engagement with our research [R1–R6; C, E], especially around how art and science can intersect to better communicate science. This has enabled members of the public to make new connections between physics and the world around them (90% of those surveyed [C]) and changed their views on how artists and scientists can work together to communicate science (>90% [C]). Audiences we interviewed at our public events said they had learned new ideas (98% [C]) and more than 80% wanted to find out more and would continue to talk and think about the event they attended. These changed perceptions help citizens appreciate and value the relevance of STEM science to their everyday lives, which is important given the vital contribution of STEM to the prosperity of society.

Our work with artists has been picked up in the mainstream media, which enabled this change in perception to reach millions more people. This includes popular Channel 4 programme Gogglebox featuring a BBC news segment on our asteroseismology research [R5] — including turning stellar oscillations data into sound, which underpins our work with artists Devine and Robson — that reached millions of people [B], as well as multiple BBC radio programmes featuring our work [B]. One presenter stated “what a totally astounding, amazing project.”

We used a range of approaches to achieve this and extend the reach to alternative audiences, including:

• Co-productions with artists as part of our PHYART@UoB programme [A, E], which engaged 15,000 people at live performances and exhibitions [A];

• Developing and making available gaming apps for mobile phones, based on gravitational wave detectors [R3, R4], which have been downloaded by the public almost 40,000 times and one game completed more than 15,000 times [D]. Freise was awarded the 2017 Education and Outreach Award by the LIGO collaboration in recognition of his pioneering efforts in creating LIGO-oriented interactive educational applications;

• Traditional forms of engagement, demonstrating particle and gravitational waves detectors [R1–R4] at Royal Society Summer Exhibitions (2014–2017) and other national science festivals, to a total audience of over 130,000 [A].

Over 20 industrial companies globally (from multinationals to SMEs), across a wide range of industry sectors, including oil and chemical, pharmaceuticals, minerals, and home and personal care, have adopted PEPT. We focus on three examples, [text removed for publication], GEA Pharma Systems and Johnson Matthey (JM).

PEPT enabled improved machine design and the development of a new tablet manufacturing process, ConsiGma, produced by GEA Pharma Systems [S3; KF4 and KF5]. Most pharmaceuticals are sold as tablets manufactured using a process called wet granulation, in which particles of the active drug substance are combined with other components to form free-flowing granules which can be fed to a tablet press. Using PEPT, GEA developed ConsiGma as a radically different continuous granulation system consisting of a twin-screw powder conveyor to which a binding liquid is added and in which screw elements perform different functions in the granulation process. GEA confirmed that this process is a more effective and efficient method stating, “in addition to the advantages of better process control and enclosed operation, adoption of ConsiGma results on average in a 40% reduction in labour costs, 60% reduction in manufacturing space compared with current industry standards and 50% energy savings resulting from reduced power requirement and heat recovery” [S3].

In 2012, GEA sold the ConsiGma continuous production line to GlaxoSmithKline (GSK), as an experimental tablet manufacturing process for its plant at Ware. This was the first of over 50 installations around the world at an average sale price of £2M each. GSK, Pfizer and AstraZeneca have all adopted the technology. The VP of GSK highlighted “some of the fantastic benefits and savings that GSK has experienced since investing in the GEA ConsiGma continuous tableting line. Savings included an 85% reduction in the amount of API [active pharmaceutical ingredient] that would normally have been used [. . .], and being able to carry out 90 experiments in one day, which would normally have taken between 3–6 months with conventional batch based development!” [S4]. Total sales of ConsiGma are in excess of £100M to date [S3]. ConsiGma is now used globally to manufacture drugs for a range of treatments including Cystic Fibrosis (Orkambi and Symdeko from Vertex Pharmaceuticals) and Acute Myeloid Leukaemia (Daurisimo, Pfizer Inc.), “with consequent benefits to the health of thousands of patients” [S3].

This new technology has environmental benefits as it replaces traditional discrete batch operations (typically crystallisation, milling, mixing, granulation, drying and tableting) — “all of which involve significant risk of failure, as well as environmental cost and risk of personal exposure to the active drug” [S3]. In contrast, ConsiGma produces “fast, continuous operation in enclosed machines with a high degree of automatic monitoring and control, a smaller physical footprint and a reduced environmental burden” [S3].

PEPT has been used in developing new products and processes with JM, a world-leading catalytic materials technology company with annual sales of £4.2B, in four key areas.

• PEPT enabled improvements in the design and operation of the multiphase catalytic reactors operated by JM’s customers in the fine chemicals and pharmaceutical industries [KF1–KF5]. This enhanced the company’s technical support for its customers and generated new sales. JM’s Scientific Consultant (lead chemical engineer) confirmed that “learning and data derived from PEPT were widely used internally, to coach technical sales personnel” and that “retained and new sales were directly attributed to the PEPT data-based service” [S5].

• Models are being used to design two major capital projects worth in excess of £300M, which rely on the improvements in modelling and scale-up of precipitation processes based on KF4 and KF5. PEPT’s work “allowed Johnson Matthey to provide improved guidelines for precipitator design, resulting in product improvements or, in one case through design improvement, allowing introduction of a new product that could otherwise not have been manufactured at scale” [S5]. In addition, the PEPT data were used to validate a reduced order Zonal Model, which is much simpler to use than computational fluid dynamics models. This “formed the basis for several new product precipitations from pilot to production scale. Without the PEPT data, JM would not have had the confidence to use these models” [S5].

• PEPT informed operational problem diagnosis and validation of models and measurement techniques in blending of precursors for vehicle Emission Control catalysts (a £2.5B sales generator for JM [S5]), based on KF4 and KF5. JM confirmed that “[t]he combined output of the PEPT study enabled a step change in the process analysis and design of washcoat and ink manufacture in JM” [S5]. It has been applied to the manufacture of inks for fuel cells and automotive glazes “to improve manufacturing performance globally and led to significant improvements” [S5].

PEPT data [KF4 and KF5] were used to validate models for processing of particulate products. Discrete Element Method (DEM) modelling is a key company capability now deployed in support of several critical manufacturing process development projects: “JM is currently using DEM as a key development and design tool for key future manufacturing technologies, and has the confidence to do so in large part due to the validation data obtained using PEPT” [S5].

Four international companies are now producing accelerator-based BNCT equipment as a direct consequence of our key findings (Neutron Therapeutics, Cancer Intelligence Care Systems (CICS), TAE Life Sciences and Sumitomo Heavy Engineering). This has led to economic and commercial impact of 2 distinct types: (1) innovation and new product development at international medical equipment companies (clinical BNCT facilities); and (2) the adoption of and investment in new BNCT technologies at facilities around the world. The significance of these developments is further attested by the demonstrable improvement in patient outcomes shown in multiple clinical trials internationally.

1) Enabling the development of a new product, a fully formed and bespoke clinical BNCT facility, by international medical equipment companies

The medical equipment company, Neutron Therapeutics, developed a clinical BNCT facility as its main commercial product using the specific lithium-copper bonding approach that we developed [KF1] in its manufacturing process. Its prototype has been demonstrated at 10s of kW of proton beam power for hundreds of hours run time with no degradation. Neutron Therapeutics’ Chief Operating Officer asserted that “The Birmingham team solved th[e] problem [of physical and thermal bonding of the lithium layer to a suitable substrate] for a copper target backing material and we have followed this approach for our commercial product. It is a critical aspect of our system and under-pins the success of our product” [E1].

The Tokyo-based company CICS is a major partner in the creation of a new BNCT facility, using a safe lithium target design, at the National Cancer Centre (NCC) in Tokyo, Japan. The NCC is the largest specialist cancer treatment hospital in Japan and spearheads standardising cancer treatment in the country. Our demonstration that the neutron beam produced by a proton beam hitting a lithium target reduced damaging side effects [KF3] materially contributed to CICS’s adoption of the lithium target technology to create the facility. Its President and CMO commented that these benefits “convinced us that the choice of a lithium target was the right one for our project” [E2], significantly influencing the commercial activity and strategic direction of the company.

The development of these BNCT facilities are materially dependant on the work of the University of Birmingham team, whose research [KF1, KF2] gave the funders confidence such that, since 2012, the NCC BNCT project has received extensive and sustained investment. It took CICS 8 years to build the equipment prototype CICS-1, at a cost of ¥2 billion, and our research [KF1 and KF2] served specifically to ensure stakeholder confidence and reassure investors that the final goal was achievable. CICS confirmed that our research reduced its financial risks: “The achievements of the team in Birmingham to produce a functioning BNCT system with a lithium target were critical for our project. They enabled us to provide the reassurance that our stakeholders required” [E2]. To date the NCC has spent ¥5 billion on the building construction and BNCT equipment. Following the success of the NCC BNCT project, CICS will deliver a second BNCT facility for Edogawa Hospital, Tokyo in March 2021.

2) Through the use of BNCT, new clinical technologies, in the form of new therapies, were developed

We have contributed to innovation within the international BNCT community, which has used our pioneering research findings [KF1–KF3] to develop BNCT therapies, with excellent efficacy. In addition to Neutron Therapeutics, which uses our specific lithium-copper bonding approach [KF1], three companies, TAE Life Sciences, Cancer Intelligence Care Systems (CICS) and Sumitomo Heavy Engineering, developed BNCT technology only after we had demonstrated that accelerator-BNCT was possible. Indeed, our research was described by the President of the International Society for Neutron Capture Therapy as “crucial in enabling BNCT as a medical therapy for incurable cancers. Motivated and inspired by (our) research, new accelerator projects have been initiated in Japan, Europe and around the World” [E3].

The Boston-based company Neutron Therapeutics, established in 2014, uses our lithium-copper bonding technique [KF1]. The company employs 25 people. In 2019, their first full clinical system was commissioned by the Helsinki University Hospital team to initially treat patients with recurrent head and neck cancers. The facility has the capacity to treat up to 2,000 patients per year. A second system will be deployed at Shonan Kamakura General Hospital in Kanagawa, Japan, in 2021. The approximate value of each clinical facility is $25 million. In 2020, Neutron Therapeutics received an additional order for an accelerator neutron source for research in the UK [E1].

Our ability to demonstrate the feasibility of BNCT as a viable clinical treatment [KF1 and KF2] impacted the commercial opportunities and investment strategy of the multi-national company, TAE Life Sciences. TAE Life Sciences raised $70 million in funding to launch a subsidiary of the nuclear fusion energy company TAE Technologies in 2018 [E4, E5]. This significant strategic investment aims to commercialise BNCT with its accelerator-based technology, making neutrons for BNCT more accessible in hospitals and hence indirectly providing better treatment for patients with incurable cancers [E4]. The company is supplying equipment to the NeuBoron facility at Xiamen Humanity Hospital in China. Construction of this facility is nearing completion and accelerator equipment is currently being installed. It will treat the first patients in 2021. In total, 14 facilities are in development or at clinical trial stage, in 8 counties around the world [E6].

New therapies are being developed using the new BNCT clinical facilities, in which CICS has invested, exploring new indications for BNCT [KF1–KF3]. These include sarcoma, malignant melanoma and pleural mesothelioma [E2]. Because of the low toxicity of the lithium target neutron beam, the CICS team are actively exploring the use of BNCT in the treatment of Alzheimer’s disease. The President and CMO commented that “I am deeply grateful to Professor Green’s prototype for guiding our developments” [E2].

The Japanese company Sumitomo Heavy Industries has also invested in BNCT facilities for therapeutic purposes, at Kyoto University Research Reactor Institute and 2 treatment rooms each at the Southern Tohoku General Hospital (Koriyama) and Osaka Medical College. In March 2020, the Japanese Ministry of Health, Labor and Welfare approved the Sumitomo accelerator system of BNCT as a treatment for patients with recurrent head and neck cancers [E7].

3) Demonstrable improvements in patient outcomes, treatment time and costs

The efficacy of BNCT has been demonstrated by multiple clinical studies by research teams internationally. The benefits of BNCT take 3 forms: the first is improved patient survival (points i–iii, below), the second is reduced toxicity (point iv) and the third is reduced treatment time and consequently costs (point v).

i) Patients with newly diagnosed glioblastoma multiforme: These brain tumours are both radio-resistant and highly infiltrating, and while the incidence is relatively low (around 4,500 cases per year in the UK), poor outcomes mean that it results in the most years of life lost of any single tumour type. Clinical results from Japan show that patients with newly diagnosed glioblastoma multiforme treated with BNCT could achieve a 2-year survival rate of 50% compared to ~30% for the best available conventional treatments [E8]. By extension, if all the ~4,500 cases per year in Britain were treated with BNCT, it would raise the number of patients alive at 2 years from ~1,350 (with conventional treatments) to 2,250. This can be extrapolated to the annual global incidence of ~200,000.

ii) Patients with glioblastoma multiforme that has recurred after first-line treatment has failed: For patients where the disease recurs and where patients are fit enough for a second-line treatment, recent data presented by a team in Japan suggests that survival at 1 year following BNCT treatment with an accelerator neutron source could approach 80% (compared with an expectation of ~35% with standard approaches) [E9]. This is a huge difference.

iii) Patients with head and neck cancers that have recurred after first-line treatment has failed: In the UK, around 12,000 patients are diagnosed with head and neck cancers each year and ~45% of these will suffer a relapse within 5 years of treatment. Conventional treatments are often so toxic that clinicians are reluctant to repeat them and so offer patients only palliative treatment and pain relief. In some regions of China, the incidence of these cancers is dramatically higher than in the UK. Trial data from Helsinki [E10] has inspired many centres, including a number of those above, to pursue BNCT. Further analysis from the Helsinki team, published in 2019 showed ~46% of patients with recurrent cancers in the head and neck to have survived 2 years following BNCT treatment and over 20% surviving 5 years [E11].

iv) Reduced toxicity: Unlike many existing treatments, BNCT shows both good disease control and low toxicity for patients with head and neck cancers. That means that BNCT can be used safely following intensive first-line treatment and can even be repeated multiple times should the disease recur (Kato et al. where BNCT treatment was repeated 3 times for 1 patient [E12]). Accelerator BNCT is even less damaging to healthy tissues [KF3] than is demonstrated in these studies which are based on neutron beams from nuclear reactors.

v) Reducing treatment time and costs: The overall benefits of using BNCT over conventional proton radiotherapy treatments are considerable. A single BNCT treatment room costs the same as a single-room proton radiotherapy facility (approximately $25 million), but can treat substantially more patients. Patients undergoing BNCT only require 1 or 2 or treatment sessions (as opposed to between 5 and 30 for proton radiotherapy) and each session only takes between 20 and 30 minutes. This means that each facility has the capacity to treat at least ~6 times more patients per year, ~2,000 in total [E1]. This simultaneously cuts capital-cost-per-patient significantly and provides better clinical outcomes than are possible with protons. Neutron Therapeutics confirmed that “[i]t is our view that this cost-effectiveness, combined with the potential to improve outcomes for patients, will lead to a significant expansion in BNCT treatment capacity in the coming years” [E1].

We have had international impact in the healthcare, security, and environmental sectors, influencing technological developments in companies (IONICON Analytical GmbH (Austria) and Kore Technology Ltd (UK)) and the adoption of breath biomarkers in the health sector (B. Braun Melsungen AG (Germany, propofol) and Owlstone Medical Ltd (UK, limonene as a liver disease biomarker)). Specifically, we have stimulated: 1) strategic change and investment to employ breath volatiles as non-invasive biomarkers; 2) innovation and the development of new technologies; and 3) the subsequent commercial adoption of these new technologies for environmental and security monitoring.

1) Changing company strategy and investment through the development of non-invasive tests for liver disease and liver function – Owlstone Medical Ltd

Owlstone Medical’s strategic change in direction was a direct result of our demonstration at an international conference [KF1 and KF2] that breath biomarkers are ideal for use in the diagnosis and monitoring of liver disease. Owlstone Medical is a Cambridge-based medical device company, whose stated vision is to “save 100,000 lives and $1.5B in healthcare costs” [E1]. We contributed to a new commercial opportunity by materially influencing the development of breath tests to detect liver disease and for determining liver function (e.g. following drug treatments and/or liver transplant [E2–E6]).

As highlighted by the company’s CEO, our work improved on Owlstone Medical’s commercial viability and competitiveness: it has “provided clear evidence of the importance of a limonene breath test and has been a driving force behind our current investment and development” [E2]. In a webinar, the CEO states that our research “really changed [his] view of what we can do in breath” and that “exogenous volatile compounds no longer should be considered as noise” [E3, E4]. The use of these exogenous breath biomarkers specifically for liver disease has been confirmed in a collaborative peer-reviewed clinical study with Owlstone and the University of Cambridge [E5] and further described in a webinar [E6].

KF1 and KF2 thus “inspired [Owlstone] to take the UoB research forward to develop a breath test for limonene” in the following clinical applications: a national screening programme for the detection of early-stage liver disease; a programme for determining liver function and monitoring after treatment; and a clinical method to determine the efficacy of drugs employed in treating non-alcoholic steatohepatitis and non-alcoholic fatty liver disease [E2 and E3].

2) Impacting the development of new medical diagnostic and monitoring products and commercial adoption of a new concept: Real-time monitoring of propofol during surgery

We directly enabled innovation and entrepreneurial activity through the design and delivery of a new commercial device at the German company B&S Analytik. Our discovery [KF3] that trace quantities of propofol and associated metabolites are present in the breath of patients undergoing surgery has been described as “a seminal investigation” providing “proof of concept of reality to the conjecture of pulmonary propofol elimination and its measurement” [E7]. B&S Analytik has developed a low-cost Ion Mobility Spectrometer (IMS) to monitor breath propofol levels during surgery based on ion-molecule processes similar to those used in our original PTR-MS study. Founded by Professor Jörg Baumbach, the company first developed the IMS which is now being marketed by B. Braun Melsungen AG under the name EDMON (Exhaled Drug Monitor) [E8], with a worldwide sales forecast of 2,000 instruments per year [E9].

Our contribution has been explicitly recognised by the founder of B&S Analytik, who stated that our work “was ultimately the scientific door opener showing the possibility to detect propofol using mass spectrometry technology in exhale which finally led to the independent development of a commercial CE marked clinical instrument based on IMS technology” [E9].

3) Technological developments improving the chemical accuracy of PTR-MS products – adopted for environmental and security real-time monitoring through collaboration with industry and Dstl

Our impact on the development and improvement of existing PTR-MS technology as a result of KF4 has arisen from direct collaboration with industry and the commercial adoption of PTR-MS [E10–E12]. PTR-MS has been adopted as a major analytical tool for the real-time detection of compounds in trace quantities (less than a ppbv) in many fields of application, ranging from atmospheric chemistry through to homeland security. The advantages of real-time analysis come with a cost in chemical selectivity. In the absence of pre-separation of compounds, as used in GC-MS, PTR-MS cannot easily distinguish between different but similar substances, leading to ‘false positive’ readings that are problematic in many applications. KF4 provided additional analytical capabilities for improved chemical selectivity to existing and new PTR-MS instruments, making them analytically more multidimensional whilst retaining their real-time analysis capabilities. This enabled the following developments.

The reduction of false positives is evidenced by two users, Dstl Fort Halstead and Dstl Porton Down, who have validated the capability of reducing false positives for explosive detection which are common in homeland security technologies, such as IMS. This improvement to the real-time (seconds) analytical accuracy (chemical specificity) of PTR-MS, was achieved by manipulating conditions within the reaction tube [KF4], allowing retrofit and thus avoiding expensive changes to older equipment. Two of the three global manufacturers of PTR-MS, Kore Technology and IONICON Analytik, adopted this improvement leading to product development and improvement. This is confirmed by Kore’s Project Manager and Senior Researcher who stated that “Chris Mayhew and his group have had an active role in affecting the content and effectiveness of different aspects of our PTR-TOF-MS instruments” [E10], have changed the company’s “fundamental understanding” of ion-molecule reactions for PTR-MS, and led to the testing and developing of new hardware and software [E10]. As a result, “every commercial PTR instrument produced by Kore now has an ion funnel, [this …] has been vital in offering us analytical flexibility to our customers” [E10; KF4].

We have also contributed to Kore’s strategic direction. The transfer of two highly skilled people into specialist roles that draw on their research has enabled take up by environmental agencies. For example, in 2019, Kore Technology built the first of seven compact PTR-MS instruments for use in China, with applications of the new technology in environmental monitoring in the more than thirty Chinese provinces [E10; KF4].

Finally, since 2019, IONICON Analytik GmbH (Austria) have re-developed their instruments to include rapid electric switching, making IONICON more competitive [E11; KF4]. This is confirmed by the company which states that our work led to “a step change in PTR-MS instrumentation, helping in IONICON’s commercial growth” and that it has “significantly contributed to IONICONs innovation and entrepreneurial activities” [E11]. Evidence of strong collaborative R&D programmes between us and IONICON Analytik GmbH and Kore Technology Ltd is provided in numerous peer-reviewed publications [E12].