̽��ֱ�� of Cambridge - Axel Zeitler

Cambridge engineers recognised with awards for pandemic service

sc604 — Mon, 17 Aug 2020 09:30:22 +0000

̽��ֱ��engineers, from the Institute of Manufacturing and the Whittle Laboratory, are among the 19 winners announced today for exceptional engineering achievements in tackling COVID-19 in the UK. In addition, two Cambridge alumni, Dr Ravi Solanki and Raymond Siems, were recognised for their work with the HEROES charity. In less than two days, their team turned an idea into a platform with genuine impact: a secure website through which more than 543,000 items of much-needed support have been provided to NHS workers, from sustainable PPE to counselling services and child care.

̽��ֱ��awards have been made to teams, organisations, individuals, collaborations and projects across all technical specialities, disciplines and career stages within the UK engineering community who have contributed to addressing the challenges of the COVID-19 pandemic.

Open Ventilator System Initiative

̽��ֱ��team behind the Open Ventilator System Initiative was recognised for their development of a high-performance ventilator for manufacture in low and middle-income countries that became the first intensive care quality ventilator to be manufactured in Africa.

In March 2020, as Covid-19 infection rates were rising dramatically in Europe, the number of infections in many low- and medium-income countries remained low. However, it was predicted that towards the summer these rates would start to increase. This was especially worrying due to the low number of ventilators available in the developing world.

In response to these fears, a team at the ̽��ֱ�� of Cambridge and a number of companies within the Cambridge cluster designed a high-performance intensive care ventilator for manufacture in low and middle-income countries. ̽��ֱ��aim was to develop a ventilator with a price point that was a factor of 10 lower than what was currently available, which could be manufactured from readily available components and which could be manufactured in-country. ̽��ֱ��result was the first clinical grade ventilator to be manufactured in Africa.

An engineering team led by Dr Tashiv Ramsander at Cambridge Aerothermal Ltd was quickly assembled at the Whittle Laboratory, and comprised people from several departments at the ̽��ֱ�� of Cambridge and a range of local companies including Cambridge Aerothermal, Beko R&D, Cambridge Instrumentation and Interneuron.

Together, this multidisciplinary team was able to solve problems such as the design of a pressure relief valve, inspired by the mixing nozzles on the Rolls-Royce Trent 1000 aircraft engine. ̽��ֱ��design removed flow instabilities, resulting in a more stable operation than any commercially available valve.

̽��ֱ��clinically driven design was developed with the help of two senior intensive care clinicians with experience of treating COVID-19. They argued that a design for developing countries needed to be more versatile than the UK government specification and the final design can operate in non-invasive, mandatory or patient-triggered ventilation modes.

For more than eight years the Whittle Laboratory has been developing a rapid technology development process for the aerospace and power generation sectors. During the pandemic this process was switched to develop a clinical grade ventilator within a week and allowing a rapid response to design changes driven by the pandemic, cost reduction and clinical demand.

̽��ֱ��final Open Ventilator design can be manufactured mostly from standard parts, anywhere in the world that it is needed.

̽��ֱ��reach and impact of COVID-19 in developing countries is not yet known, but this new design - the first intensive care quality ventilator to be manufactured in Africa - could prove to be a gamechanger when it comes to a host of conditions including pneumonia, as well as COVID-19. Childhood pneumonia killed 162,000 children in Nigeria alone in 2018.

There are very few ventilators in Africa, due to their high cost, inability to operate in harsh environments and a lack of local maintenance expertise. ̽��ֱ��team realised these problems could be solved by manufacturing the equipment in Africa. ̽��ֱ��Cambridge engineering team assembled a wider manufacturing team that includes Defy and Denel Land Systems in South Africa, Beko R&D and Prodrive in the UK and Arçelik in Turkey. This team delivered the first 20 preproduction ventilators in South Africa in June.

“ ̽��ֱ��result is a design that will save countless lives in the developing world where ventilators are scarce and many that exist cannot achieve the quality of performance that the Open Ventilator offers,” said Professor Richard Prager, head of the Department of Engineering. “It is a scalable solution. ̽��ֱ��high-performance open-source design will enable companies across the world to make systems wherever they are needed, and at a price that is compatible with the local healthcare systems.”

Institute for Manufacturing

̽��ֱ��IfM team helped local hospitals to make the best use of their resources, streamlining logistics for sourcing and storing vital PPE, informing decision-making on emergency demand, and developing a ventilator sharing system to be used in emergencies.

As hospitals scrambled to make the necessary operational changes needed to accommodate COVID-19 patients, a team of staff and students from the Institute for Manufacturing (IfM) at the ̽��ֱ�� of Cambridge was there to help. Working with clinicians and senior healthcare managers to assess the immediate and emerging operational challenges facing local hospitals, they identified where these could be addressed through the application of engineering capabilities and coordinated the roll-out of solutions.

̽��ֱ��IfM team addressed three groups of tasks between March and May in the areas of hospital logistics, personal protective equipment (PPE) delivery and intensive care unit (ICU) equipment development.

In the hospital logistics area, the team applied industrial engineering approaches to COVID-related challenges including modelling in-hospital patient flows, redesigning COVID-19 testing procedures and managing oxygen supplies to the wards.

Understanding oxygen flow through the local hospital involved examining pipes and their layout, then analysing usage by ventilator type and patient need, as well as modelling supply and demand. ̽��ֱ��in-depth work of the IfM team enabled the hospital’s clinical and estates teams to identify and address various bottlenecks and improve operational efficiency.

̽��ֱ��team also looked at the design, setup and management of a temporary logistics hub for coordinating the delivery of millions of items of donated PPE and assessed the production capabilities of local manufacturers to increase flexibility of PPE supplies for local hospitals.

In conjunction with anaesthetists at Royal Papworth Hospital, they also devised an active ventilator sharing system in case there were not enough ventilators available during the COVID-19 outbreak. This involved the accelerated design, prototyping and in-hospital testing of an active ventilator sharing system in just four weeks.

Duncan McFarlane, Professor of Industrial Information Engineering at the IfM, led the team as they engaged with senior clinical and management teams within local hospitals to understand their needs and implement effective and collaborative ways of working. This involved joining the hospital's regular operations planning meetings and running daily project reviews with key hospital personnel during the peak COVID-19 surge, as well as working directly with clinicians in areas such as COVID-19 test processes, ward oxygen supply, and equipment design.

̽��ֱ��IfM team helped local hospitals make the best use of their resources and streamlined logistics for sourcing and storing vital PPE and other issues, enabling healthcare providers who were already feeling the strain to address pressing operational challenges.

In addition, the IfM provided analytical approaches for informing decision making at Cambridge ̽��ֱ�� Hospital (CUH) on emergency demand. ̽��ֱ��Trust is also using the team’s findings to forecast changes to demand for beds, equipment and staff when social distancing measures are relaxed or modified further. ̽��ֱ��hospital said the engineers brought diversity of perspective and a joint CUH–IfM panel has been initiated so that the hospitals and the IfM can continue working together for mutual benefit after the pandemic.

“ ̽��ֱ��team gave key support efficiently and skilfully when it was most needed, with no fuss and maximum impact: engineering at its best,” said Professor Prager. “ ̽��ֱ��team found a way to work with the clinicians without taking up too much clinical time. They found the problems that needed solving and got on with solving them. They stepped up when they were needed and made a real difference. For this, we should be proud of them.”

Professor Tim Minshall, Dr John C Taylor Professor of Innovation and Head of the Institute for Manufacturing, said: “It makes me so proud to see the way in which our students and staff – academic, research and administrative – were able to rapidly understand and help address the operational challenges facing the amazing teams at Addenbrooke’s and Royal Papworth during this crisis.

“We are also delighted that there is such enthusiasm from both CUH and the IfM to build upon this experience and to develop ongoing collaboration in applying industrial engineering capabilities to healthcare system needs.”

How you can support Cambridge's COVID-19 research effort

Donate to support COVID-19 research at Cambridge

Two teams of Cambridge engineers have been recognised by the Royal Academy of Engineering for their work during the COVID-19 pandemic with the President’s Special Award for Pandemic Service.

Jude Palmer/Royal Academy of Engineering

̽��ֱ��OVSI team

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Open-source ventilator designed by Cambridge team for use in low- and middle-income countries

sc604 — Mon, 20 Apr 2020 10:44:38 +0000

Built primarily for use in low- and middle-income countries, the OVSI ventilator can be cheaply and quickly manufactured from readily available components. Current ventilators are expensive and difficult to fix, but an open-source design will allow users to adapt and fix the ventilators according to their needs and, by using readily available components, the machines can be built quickly across Africa in large numbers. ̽��ֱ��cost per device is estimated to be around one-tenth of currently available commercial systems.

̽��ֱ��first ventilators will be delivered in May by a team of South Africa-based companies led by Defy, a leading southern African manufacturer of domestic appliances, and Denel, a major state-owned company.

Recent tentative estimates published by the WHO have suggested that there could be as many as 10 million cases of COVID-19 in Africa within three to six months, resulting in anywhere between 300,000 and 3.3 million deaths. There are 10 countries in Africa that do not have any ventilators at all and according to the WHO, it is estimated that there are fewer than 2,000 working ventilators across 41 countries in Africa.

“Fulfilling the unique requirements of local clinicians was key to this project,” said Professor Axel Zeitler from the Department of Chemical Engineering and Biotechnology, and OVSI team lead. “Clinicians told us the ventilator needed to cover the wide spectrum of patient ventilation requirements, and therefore work in three modes – non-invasive, mandatory or patient-triggered ventilation.

“We also know that oxygen availability varies within countries, hospitals and wards. ̽��ֱ��system must use the smallest amount of oxygen possible, but include the potential to add an oxygen concentrator.”

̽��ֱ��Open Ventilator System Initiative is a consortium of academics, engineers, intensive care medics, innovators and industry partners across the UK and Africa. Formed in March this year, the initiative has grown quickly from an initial idea at the ̽��ֱ�� of Cambridge to a team of 60 individuals contributing remotely.

̽��ֱ��team is being advised by a panel of clinical experts including physicians in Uganda, Kenya, the DRC, South Africa and the UK. ̽��ֱ��clinical partnerships were established with the support of the Cambridge-Africa programme and Cambridge Global Health Partnerships. ̽��ֱ��ventilator was designed and built by a team based at the ̽��ֱ�� of Cambridge’s Whittle Laboratory.

“Critical to this project has been the speed of technology development,” said Professor Robert Miller, Director of the Whittle Laboratory. “In recent years, the primary focus of the Whittle Laboratory has been to accelerate the process of technology development. By merging the digital and physical systems integral to the technology development process and by using Formula One-style teams, we’ve cut the amount of time this takes by a factor of 10 to 100. This capability has been key to delivering the OVSI ventilator.”

̽��ֱ��prototype is currently being developed further into a version that can be easily mass-produced by Prodrive Ltd, a British motorsport and advanced engineering group based in Banbury, Oxfordshire. It has been thoroughly tested at the National Physical Laboratory in Teddington and passed the MHRA test specifications with flying colours. ̽��ֱ��OVSI team is currently working on securing regulatory approval for the device.

̽��ֱ��first manufacture will be led by Defy Ltd and Denel Ltd in South Africa. Evren Albas, CEO of Defy Appliances in South Africa said, “Defy’s flexible manufacturing capabilities in Africa, together with the design and development expertise of the consortium with whom we are partnering, will allow us to fast-track ventilator production and distribution. Teams are working around the clock to start production by May.”

“While the immediate need is to save lives in the context of the COVID-19 pandemic, we wanted something that will be useful to healthcare workers around the world going forward,” said Dr Lara Allen, CEO of the Centre for Global Equality and a founding member of the OVSI team. “It’s often the case that those living on less than $4 per day are excluded from the innovation process. As a result, many well-meaning innovations are not what is needed or wanted by the intended beneficiaries and end up not being used. This is disappointing for designers, a waste of humanitarian resources, and low-resource communities continue to go without the support they desperately need. This is why taking an inclusive innovation approach is vital for sustainable impact.”

Present efforts to adapt the design for low- and middle-income countries include collaboration with the long-term inclusive innovation partners at the Bahir Dar Institute of Technology, at Bahir Dar ̽��ֱ�� in Ethiopia, and the Science & Technology Park at the ̽��ֱ�� of Nairobi in Kenya.

OVSI will work with partner countries in Africa and elsewhere to enable local manufacturing and maintenance of the ventilator, and to design, prototype and gain regulatory approval for system upgrades.

How you can support Cambridge's COVID-19 research effort

Donate to support COVID-19 research at Cambridge

In response to the COVID-19 pandemic, a team at the ̽��ֱ�� of Cambridge has designed an open-source ventilator in partnership with local clinicians, engineers and manufacturers across Africa that is focused to address the specific needs for treating COVID-19 patients and is a fully functioning system for use after the pandemic.

Fulfilling the unique requirements of local clinicians was key to this project

Axel Zeitler

Open-source ventilator designed for use in low- and middle-income countries

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Method to predict drug stability could lead to more effective medicines

sc604 — Mon, 05 Mar 2018 14:10:10 +0000

̽��ֱ��researchers, from the Universities of Cambridge and Copenhagen, have developed a new method to solve an old problem: how to predict when and how a solid will crystallise. Using optical and mechanical measuring techniques, they found that localised movement of molecules within a solid is ultimately responsible for crystallisation.

This solution to the problem was first proposed in 1969, but it has only now become possible to prove the hypothesis. ̽��ֱ��results are reported in two papers in Physical Chemistry Chemical Physics and ̽��ֱ��Journal of Physical Chemistry B.

Solids behave differently depending on whether their molecular structure is ordered (crystal) or disordered (glass). Chemically, the crystal and glass forms of a solid are exactly the same, but they have different properties.

One of the desirable properties of glasses is that they are more soluble in water, which is especially useful for medical applications. To be effective, medicines need to be water-soluble, so that they can be dissolved within the body and reach their target via the bloodstream.

“Most of the medicines in use today are in the crystal form, which means that they need extra energy to dissolve in the body before they enter the bloodstream,” said study co-author Professor Axel Zeitler from Cambridge’s Department of Chemical Engineering & Biotechnology. “Molecules in the glass form are more readily absorbed by the body because they can dissolve more easily, and many glasses that can cure disease have been discovered in the past 20 years, but they’re not being made into medicines because they’re not stable enough.”

After a certain time, all glasses will undergo spontaneous crystallisation, at which point the molecules will not only lose their disordered structure, but they will also lose the properties that made them effective in the first place. A long-standing problem for scientists has been how to predict when crystallisation will occur, which, if solved, would enable the widespread practical application of glasses.

“This is a very old problem,” said Zeitler. “And for pharmaceutical companies, it’s often too big of a risk. If they develop a drug based on the glass form of a molecule and it crystallises, they will not only have lost a potentially effective medicine, but they would have to do a massive recall.”

In order to determine when and how solids will crystallise, most researchers had focused on the glass transition temperature, which is the temperature above which molecules can move in the solid more freely and can be measured easily. Using a technique called dynamic mechanical analysis as well as terahertz spectroscopy, Zeitler and his colleagues showed that instead of the glass transition temperature_, the molecular motions occurring until a lower temperature threshold, are responsible for crystallisation.

These motions are constrained by localised forces in the molecular environment and, in contrast to the relatively large motions that happen above the glass transition temperature_, the molecular motions above the lower temperature threshold are much subtler. While the localised movement is tricky to measure, it is a key part of the crystallisation process.

Given the advance in measurement techniques developed by the Cambridge and Copenhagen teams, drug molecules that were previously discarded at the pre-clinical stage can now be tested to determine whether they can be brought to the market in a stable glass form that overcomes the solubility limitations of the crystal form.

“If we use our technique to screen molecules that were previously discarded, and we find that the temperature associated with the onset of the localised motion is sufficiently high, we would have high confidence that the material will not crystallise following manufacture,” said Zeitler. “We could use the calibration curve that we describe in the second paper to predict the length of time it will take the material to crystallise.”

̽��ֱ��research has been patented and is being commercialised by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. ̽��ֱ��research was funded by the Engineering and Physical Sciences Research Council (EPSRC).

References:
Michael T. Ruggiero et al. ‘ ̽��ֱ��significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation’ Physical Chemistry Chemical Physics, 19, 30039-30047 (2017). DOI: 10.1039/c7cp06664c

Eric Ofosu Kissi et al. ‘ ̽��ֱ��glass transition temperature of the β-relaxation as the single predictive parameter for recrystallization of neat amorphous drugs.’ ̽��ֱ��Journal of Physical Chemistry B (2018). DOI: 10.1021/acs.jpcb.7b10105

Researchers from the UK and Denmark have developed a new method to predict the physical stability of drug candidates, which could help with the development of new and more effective medicines for patients. ̽��ֱ��technology has been licensed to Cambridge spin-out company TeraView, who are developing it for use in the pharmaceutical industry in order to make medicines that are more easily released in the body.

This is a very old problem, and for pharmaceutical companies, it’s often too big of a risk.

Axel Zeitler

Gatis Gribusts

Medication

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