̽��ֱ�� of Cambridge - technology transfer

Team’s hip replacement surgery invention is set to be world first

sc604 — Fri, 13 Sep 2024 11:18:10 +0000

They have just won an award to develop their technology, which aims to make hip surgery more precise and deliver better and longer-lasting outcomes – which is good for patients and the NHS.

̽��ֱ��National Institute for Health and Care Research (NIHR) has awarded a £1.4 million Invention for Innovation (i4i) Product Development Award to advance work on the team’s “smart” joint “trial liner”.

̽��ֱ��sensors measure forces passing through the hip joint to help the surgeon assess and balance the soft tissues, which aids the accurate positioning of the implant.

Once measurements are complete using the wireless surgical aid, the surgeon marks the ideal position for the implant, removes the smart trial liner, and completes the operation.

There are currently no technologies that can deliver such readings during an operation and in real-time, and instead surgeons balance the joint based on feel and anatomical landmarks.

This is despite over two million total hip replacements being performed annually, with the number constantly rising due to increasing lifespans. Younger patients are starting to need hip replacements as well, so implants need to withstand higher stresses and last longer, to avoid spiralling into a vicious circle of revision surgery and higher rates of dissatisfaction.

Driving this clinical initiative is the chief investigator from Cambridge ̽��ֱ�� Hospitals (CUH) NHS Foundation Trust, Consultant orthopaedic surgeon, clinical and research lead of the Young Adult Hip Service, and Affiliate Associate Professor at the ̽��ֱ�� of Cambridge Vikas Khanduja.

̽��ֱ��technology development is being overseen by Professor Sohini Kar-Narayan from Cambridge’s Department of Materials Science and Metallurgy, together with Dr Jehangir Cama, who is leading on translational and commercialisation activities. They are joined by Consultant clinical scientist and CUH head of clinical engineering, Professor Paul White.

“We’re really looking forward to this next phase of product development that will see us move towards an actual product that is fit for clinical use, and that has the potential to revolutionise joint replacement surgery,” said Kar-Narayan.

“This funding will bring together wide-ranging expertise to help us further develop our prototype, bringing this technology closer to clinical use,” said Cama.

̽��ֱ��team currently has a prototype version of the device, which has been validated in the laboratory and in other tests. However, the NIHR award is important for further development and finalisation of the design and compliance with regulations before it can be tested in a living patient.

̽��ֱ��team’s underlying sensor technology intellectual property has been protected via a patent application filed by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm.

“This is a fantastic example of Cambridge’s entrepreneurial clinicians, academics and their institutions working together with forward-looking funders to create a positive impact for markets, society and importantly patients,” said Dr Terry Parlett, Commercialisation Director at Cambridge Enterprise.

Adapted from a CUH press release.

Technology that could transform the future of hip replacement surgery is being pioneered by a team of experts in Cambridge.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY via Getty Images

Illustration of a human hip joint

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Three Cambridge researchers awarded Royal Academy of Engineering Chair in Emerging Technologies

sc604 — Thu, 14 Mar 2024 11:06:52 +0000

From atomically thin semiconductors for more energy-efficient electronics, to harnessing the power of the sun by upcycling biomass and plastic waste into sustainable chemicals, their research encompasses a variety of technological advances with the potential to deliver wide-ranging benefits.

Funded by the UK Department for Science, Innovation and Technology, the Academy’s Chair in Emerging Technologies scheme aims to identify global research visionaries and provide them with long-term support. Each £2,500,000 award covers employment and research costs, enabling each researcher to focus on advancing their technology to application in a strategic manner for up to 10 years.

Since 2017, the Chair in Emerging Technologies programme has awarded over £100 million to Chairs in 16 universities located across the UK. Of the four Chairs awarded in this round, three were awarded to Cambridge researchers.

Professor Manish Chhowalla FREng, from the Department of Materials Science and Metallurgy, is developing ultra-low-power electronics based on wafer-scale manufacture of atomically thin (or 2D) semiconductors. ̽��ֱ��atomically thin nature of the 2D semiconductors makes them ideal for energy-efficient electronics. To reap their benefits, complementary metal oxide semiconductor processes will be developed for integration into ultra-low power devices.

Professor Nic Lane and his team at the Department of Computer Science and Technology, are working to make the development of AI more democratic by focusing on AI methods that are less centralised and more collaborative, and offer better privacy protection.

Their project, nicknamed DANTE, aims to encourage wider and more active participation across society in the development and adoption of AI techniques.

“Artificial intelligence (AI) is evolving towards a situation where only a handful of the largest companies in the world can participate,” said Lane. “Given the importance of this technology to society this trajectory must be changed. We aim to invent, popularise and commercialise core new scientific breakthroughs that will enable AI technology in the future to be far more collaborative, distributed and open than it is today.”

̽��ֱ��project will focus on developing decentralised forms of AI that facilitate the collaborative study, invention, development and deployment of machine learning products and methods, primarily between collections of companies and organisations. An underlying mission of DANTE is to facilitate advanced AI technology remaining available for adoption in the public sphere, for example in hospitals, public policy, and energy and transit infrastructure.

Professor Erwin Reisner, from the Yusuf Hamied Department of Chemistry, is developing a technology, called solar reforming, that creates sustainable fuels and chemicals from biomass and plastic waste. This solar-powered technology uses only waste, water and air as ingredients, and the sun powers a catalyst to produce green hydrogen fuel and platform chemicals to decarbonise the transport and chemical sectors. A recent review in Nature Reviews Chemistry gives an overview of plans for the technology.

“ ̽��ֱ��generous long-term support provided by the Royal Academy of Engineering will be the critical driver for our ambitions to engineer, scale and ultimately commercialise our solar chemical technology,” said Reisner. “ ̽��ֱ��timing for this support is perfect, as my team has recently demonstrated several prototypes for upcycling biomass and plastic waste using sunlight, and we have excellent momentum to grasp the opportunities arising from developing these new technologies. I also hope to use this Chair to leverage further support to establish a circular chemistry centre in Cambridge to tackle our biggest sustainability challenges.”

“I am excited to announce this latest round of Chairs in Emerging Technology,” said Dr Andrew Clark, Executive Director, Programmes, at the Royal Academy of Engineering. “ ̽��ֱ��mid-term reviews of the previous rounds of Chairs are providing encouraging evidence that long-term funding of this nature helps to bring the groundbreaking and influential ideas of visionary engineers to fruition. I look forward to seeing the impacts of these four exceptionally talented individuals.”

Three Cambridge researchers – Professors Manish Chhowalla, Nic Lane and Erwin Reisner – have each been awarded a Royal Academy of Engineering Chair in Emerging Technologies, to develop emerging technologies with high potential to deliver economic and social benefits to the UK.

̽��ֱ�� of Cambridge

L-R: Manish Chhowalla, Nic Lane, Erwin Reisner

Yes

Inflatable, shape-changing spinal implants could help treat severe pain

sc604 — Fri, 25 Jun 2021 17:14:34 +0000

A team of engineers and clinicians has developed an ultra-thin, inflatable device that can be used to treat the most severe forms of pain without the need for invasive surgery.

‘Vegan spider silk’ provides sustainable alternative to single-use plastics

sc604 — Thu, 10 Jun 2021 09:00:00 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, created a polymer film by mimicking the properties of spider silk, one of the strongest materials in nature. ̽��ֱ��new material is as strong as many common plastics in use today and could replace plastic in many common household products.

̽��ֱ��material was created using a new approach for assembling plant proteins into materials that mimic silk on a molecular level. ̽��ֱ��energy-efficient method, which uses sustainable ingredients, results in a plastic-like free-standing film, which can be made at industrial scale. Non-fading ‘structural’ colour can be added to the polymer, and it can also be used to make water-resistant coatings.

̽��ֱ��material is home compostable, whereas other types of bioplastics require industrial composting facilities to degrade. In addition, the Cambridge-developed material requires no chemical modifications to its natural building blocks, so that it can safely degrade in most natural environments.

̽��ֱ��new product will be commercialised by Xampla, a ̽��ֱ�� of Cambridge spin-out company developing replacements for single-use plastic and microplastics. ̽��ֱ��company will introduce a range of single-use sachets and capsules later this year, which can replace the plastic used in everyday products like dishwasher tablets and laundry detergent capsules. ̽��ֱ��results are reported in the journal Nature Communications.

For many years, Professor Tuomas Knowles in Cambridge’s Yusuf Hamied Department of Chemistry has been researching the behaviour of proteins. Much of his research has been focused on what happens when proteins misfold or ‘misbehave’, and how this relates to health and human disease, primarily Alzheimer’s disease.

“We normally investigate how functional protein interactions allow us to stay healthy and how irregular interactions are implicated in Alzheimer’s disease,” said Knowles, who led the current research. “It was a surprise to find our research could also address a big problem in sustainability: that of plastic pollution.”

As part of their protein research, Knowles and his group became interested in why materials like spider silk are so strong when they have such weak molecular bonds. “We found that one of the key features that gives spider silk its strength is the hydrogen bonds are arranged regularly in space and at a very high density,” said Knowles.

Co-author Dr Marc Rodriguez Garcia, a postdoctoral researcher in Knowles’ group who is now Head of R&D at Xampla, began looking at how to replicate this regular self-assembly in other proteins. Proteins have a propensity for molecular self-organisation and self-assembly, and plant proteins, in particular, are abundant and can be sourced sustainably as by-products of the food industry.

“Very little is known about the self-assembly of plant proteins, and it’s exciting to know that by filling this knowledge gap we can find alternatives to single-use plastics,” said PhD candidate Ayaka Kamada, the paper’s first author.

̽��ֱ��researchers successfully replicated the structures found on spider silk by using soy protein isolate, a protein with a completely different composition. “Because all proteins are made of polypeptide chains, under the right conditions we can cause plant proteins to self-assemble just like spider silk,” said Knowles, who is also a Fellow of St John's College. “In a spider, the silk protein is dissolved in an aqueous solution, which then assembles into an immensely strong fibre through a spinning process which requires very little energy.”

“Other researchers have been working directly with silk materials as a plastic replacement, but they’re still an animal product,” said Rodriguez Garcia. “In a way, we’ve come up with ‘vegan spider silk’ – we’ve created the same material without the spider.”

Any replacement for plastic requires another polymer – the two in nature that exist in abundance are polysaccharides and polypeptides. Cellulose and nanocellulose are polysaccharides and have been used for a range of applications, but often require some form of cross-linking to form strong materials. Proteins self-assemble and can form strong materials like silk without any chemical modifications, but they are much harder to work with.

̽��ֱ��researchers used soy protein isolate (SPI) as their test plant protein, since it is readily available as a by-product of soybean oil production. Plant proteins such as SPI are poorly soluble in water, making it hard to control their self-assembly into ordered structures.

̽��ֱ��new technique uses an environmentally friendly mixture of acetic acid and water, combined with ultrasonication and high temperatures, to improve the solubility of the SPI. This method produces protein structures with enhanced inter-molecular interactions guided by the hydrogen bond formation. In a second step, the solvent is removed, which results in a water-insoluble film.

̽��ֱ��material has a performance equivalent to high-performance engineering plastics such as low-density polyethylene. Its strength lies in the regular arrangement of the polypeptide chains, meaning there is no need for chemical cross-linking, which is frequently used to improve the performance and resistance of biopolymer films. ̽��ֱ��most commonly used cross-linking agents are non-sustainable and can even be toxic, whereas no toxic elements are required for the Cambridge-developed technique.

“This is the culmination of something we’ve been working on for over ten years, which is understanding how nature generates materials from proteins,” said Knowles. “We didn’t set out to solve a sustainability challenge -- we were motivated by curiosity as to how to create strong materials from weak interactions.”

“ ̽��ֱ��key breakthrough here is being able to control self-assembly, so we can now create high-performance materials,” said Rodriguez Garcia. “It’s exciting to be part of this journey. There is a huge, huge issue of plastic pollution in the world, and we are in the fortunate position to be able to do something about it.”

Xampla's technology has been patented by Cambridge Enterprise, the ̽��ֱ��'s commercialisation arm. Cambridge Enterprise and Amadeus Capital Partners co-led a £2 million seed funding round for Xampla, joined by Sky Ocean Ventures and the ̽��ֱ�� of Cambridge Enterprise Fund VI, which is managed by Parkwalk.

Reference:
A. Kamada et al. ‘Self-assembly of plant proteins into high-performance multifunctional nanostructured films.’ Nature Communications (2021). DOI: 10.1038/s41467-021-23813-6

Researchers have created a plant-based, sustainable, scalable material that could replace single-use plastics in many consumer products.

It was a surprise to find our research could also address a big problem in sustainability: that of plastic pollution

Tuomas Knowles

Xampla

Packaging incorporating Xampla's plant-based plastic

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Two new initiatives to boost economic value from university research

Anonymous — Thu, 16 Jul 2020 08:00:00 +0000

̽��ֱ��grants, from the Research England Development (RED) Fund, will support two new programmes: TenU and a new Policy Evidence Unit for ̽��ֱ�� Commercialisation and Innovation (UCI), which will be based at Cambridge’s Institute for Manufacturing (IfM).

TenU will bring together the heads of technology transfer offices (TTOs) from ten of the world’s leading universities to share expertise and experience to develop, improve, and disseminate best practice in research commercialisation. UCI will undertake research to create the evidence base for informing research commercialisation policy for government and universities. ̽��ֱ��two groups will work closely in areas of mutual interest.

Research from the TenU universities has led to world-changing innovations such as rapid whole-genome sequencing, the page rank algorithm technology that became the basis for Google, the world’s first artificial vaccine against viral hepatitis B, fibre optics, one of the most widely used medications for HIV treatment, and programmed T cell therapies.

As countries work to rebuild their economies in the wake of COVID-19, university TTOs will play a critical role in turning early-stage, research-based innovations into new products and services across different sectors. In the UK, the Industrial Strategy has identified universities as key drivers of innovation.

“We welcome this vital support from Research England, which enables us to continue to share, compare, and advance international best practice in university research commercialisation for the benefit of our economies and societies locally, nationally, and globally,” said Tony Raven, CEO of Cambridge Enterprise, the ̽��ֱ�� of Cambridge’s commercialisation arm.

Apart from Cambridge, the other members of TenU are Columbia, Edinburgh, Imperial College London, Leuven, Manchester, MIT, Stanford, Oxford, and ̽��ֱ�� College London.

̽��ֱ��Policy Evidence Unit for ̽��ֱ�� Commercialisation and Innovation (UCI), based at Cambridge’s Institute for Manufacturing, will help to drive a step change in universities’ contributions to delivering increased R&D and innovation in the UK.

̽��ֱ��new unit will be developed in partnership with the Centre for Science, Technology and Innovation Policy (CSTI) and the National Centre for Universities and Business (NCUB). It will support the needs of government departments, funding agencies, and universities for better data, evidence, and expert insights, to develop more effective approaches for university commercialisation and innovation.

̽��ֱ��needs for better evidence are growing as we move from the immediate COVID-19 crisis into the longer-term economic recovery period, and as the government looks to maximise the value realised from its investment in the research base. Universities need to find new ways of working with businesses, investors and others to open up opportunities, address emerging innovation challenges, and improve productivity. To unlock this potential, governments will have to adapt policies and funding programmes to become key enabling partners in this process.

Working closely with key stakeholders, UCI will initially focus on three areas:

Developing an evidence base on how the COVID-19 induced economic crisis is affecting universities’ abilities to contribute to innovation and identify possible actions to ensure they are able to play a strategic and active role in the national economic recovery.
Improving our understanding of the research-to-innovation commercialisation journeys and examine how policies and university practices could be strengthened to deliver increased value to the UK.
Advancing the data and metrics available to better capture the performance of universities in delivering economic and social impacts through their commercialisation activities to facilitate more effective benchmarking and evaluation of performance.

Tomas Ulrichsen, Director of the new Policy Evidence Unit for ̽��ֱ�� Commercialisation and Innovation, said: “I am delighted to bring expertise from CSTI, the ̽��ֱ�� of Cambridge, and NCUB together to establish this important new policy evidence unit. ̽��ֱ��grant from the Research England Development Fund will enable us to support policymakers, funders, and universities with better and more targeted evidence and expert insight, to consider how to build on and adapt their approaches to university-driven commercialisation and innovation. This will help economies across the UK recover, reconfigure, and thrive through the economic recovery following the COVID-19 pandemic.”

“In line with the UK Government’s R&D Roadmap, Research England as part of UK Research and Innovation needs to demonstrate we are world class at securing economic and social benefits from research,” said David Sweeney, Executive Chair of Research England. “ ̽��ֱ�� technology transfer is at the heart of that. Research England funding for TenU will help showcase best practice at the global cutting edge, with the new UCI policy unit providing critical evidence and metrics. We look forward to deepening these international links.”

Research England has awarded two grants, totalling £1.5 million, to support programmes working to increase the economic value and social impacts from university research, both in the UK and internationally. ̽��ֱ��funds will be administered by the ̽��ֱ�� of Cambridge.

Photo by Joshua Sortino on Unsplash

Look up

Yes

A new model for industrial–academic partnership

lw355 — Fri, 01 Jan 2010 15:54:49 +0000

PneumaCare is solving the problem of how to monitor lung function in babies, children and chronically sick patients using a non-invasive medical device. ̽��ֱ��idea for the device, which combines innovative image processing with technologies from the gaming and movie industry, has been developed by a consortium of experts that includes Dr Joan Lasenby at the Department of Engineering, Dr Richard Iles at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Dr Colin Smithers of Plextek Ltd.

̽��ֱ��company represents a new and interesting departure from the usual spin-out model, as Dr Gareth Roberts, PneumaCare Chief Executive, explained: ‘Recognising an unmet medical need, the company consulted and utilised ̽��ֱ�� expertise to create an innovative product. We have developed a close working relationship with the academics involved and, to cement this relationship, the academic partners have become equity holders. ̽��ֱ��success of this model ensures that the ̽��ֱ�� shares in the company’s success.’

PneumaCare will present data from its first product, PneumaScan™, over the next few months. ‘We believe that the PneumaScan will make monitoring feasible, effective and simpler, leading to better patient recovery,’ said Dr Roberts. ‘We have generated considerable interest in the investment community and are poised to go into full clinical development and medical trials.’

Part of this investment has come from the newly created ̽��ֱ�� of Cambridge Discovery Fund, which is managed by Cambridge Enterprise Ltd. ̽��ֱ��fund was created to smooth the path of transferring ̽��ֱ��-related technologies for the benefit of society by providing proof of concept, pre-licence, pre-seed and seed investments, and is capitalised from donations through the ̽��ֱ�� of Cambridge 800th Anniversary campaign.

For more information about the ̽��ֱ�� of Cambridge Discovery Fund, please contact Cambridge Enterprise Ltd (Tel: +44 (0)1223 760339; email: enquires@enterprise.cam.ac.uk) or visit www.enterprise.cam.ac.uk/

PneumaCare, the first company to receive funding from the ̽��ֱ�� of Cambridge Discovery Fund, is a new model for utilising academic expertise.

Cambridge Enterprise

Discovery Fund

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Yes

Campath: from innovation to impact

bjb42 — Sat, 01 Aug 2009 00:00:00 +0000

̽��ֱ��journey taken by Campath-1H from the laboratory to its imminent use as a new treatment for multiple sclerosis (MS) is deeply rooted in fundamental research and illustrates the role that academic research plays throughout the development of new innovations. In the late 1970s, Professor Herman Waldmann, then a lecturer in the Department of Pathology at the ̽��ֱ�� of Cambridge and now Head of the Sir William Dunn School of Pathology, Oxford, was applying for his first Medical Research Council programme grant. ‘I was interested in understanding immunological tolerance [see Glossary below],’ remembers Waldmann, a process that was poorly understood at that time, as were many other aspects of the human immune system.

̽��ֱ��immune system is a network of many cell types that protect the body from bacteria and other disease-causing organisms (pathogens). When a pathogen enters the body and infects human cells, immune system cells that circulate in the blood called T and B lymphocytes detect its presence by binding to pathogen-specific molecules called antigens and become activated. ̽��ֱ��activated T lymphocytes kill the pathogen-infected cells directly or help the activated B lymphocytes make antibodies, secreted proteins that recognise specific antigens. These antibodies coat the pathogens, which labels them for destruction by other immune system cells through processes that immunologists call effector mechanisms.

Although a person’s immune system responds quickly to pathogens, it usually ignores self antigens, molecules that are present in the person’s own body. This lack of response is called tolerance. In 1978, says Waldmann, ‘people thought that to make a good immune response, lymphocytes had to cooperate with each other and that if there wasn’t good cooperation between lymphocytes, the default state was tolerance.’

One way to investigate tolerance, therefore, might be to reduce the number of lymphocytes in an experimental animal and then expose the animal to a new antigen. If this theory about tolerance was right, the animal should become tolerant to the antigen. But how could the number of lymphocytes in an animal be reduced?

̽��ֱ��approach Waldmann took was to make an anti-lymphocyte antibody using a technique that had recently been developed by Dr César Milstein at the nearby Laboratory of Molecular Biology. By fusing myeloma cells (cancer cells that develop from B lymphocytes) with cells from the spleen, Milstein had managed to make cell lines that indefinitely produced large amounts of a single antibody. Such monoclonal antibodies were ideal for Waldmann’s experiment.

‘ ̽��ֱ��immediate medical applications of this experiment were very clear,’ says Waldmann. ‘If it worked, it would provide a way to improve bone marrow transplants.’ These transplants are used to ‘rescue’ cancer patients whose blood system has been destroyed by radiotherapy. Donated bone marrow rescues these patients because it contains stem cells, precursor cells that can provide the recipient with a new blood system. Unfortunately, donated bone marrow also contains mature lymphocytes, which can attack the patient. Waldmann reasoned that, by using a monoclonal antibody to remove mature lymphocytes from the donor marrow, this potentially fatal ‘graft-versus-host disease’ could be avoided. Importantly, however, Waldmann also saw his work as a way to investigate basic immunological mechanisms.

Campath antibodies and bone marrow transplants

Late in 1979, Waldmann and his team immunised a rat with human lymphocytes and fused its spleen cells with a rat myeloma cell line. Over Christmas, Waldmann isolated several antibody-producing cell lines from this Campath-1 fusion (‘Campath’ stands for Cambridge Pathology) and his team set to work to identify an antibody that could kill mature T lymphocytes without damaging the bone marrow stem cells. In particular, the researchers looked for an antibody that could activate complement, one of the immune system’s effector mechanisms. ̽��ֱ��monoclonal antibody that best met these criteria was an ‘IgM’ antibody. B lymphocytes can make several different types of antibody (isotypes), each of which behaves differently in terms of which immune effector mechanisms it interacts with to destroy pathogens. This particular IgM (Campath-1M) activated complement efficiently and almost completely eliminated T lymphocytes in test tubes.

̽��ֱ��first bone marrow transplants that used Campath-1M for T-lymphocyte depletion were performed in the early 1980s. Bone marrow taken from donors was treated with Campath-1M in test tubes and the T-lymphocyte-depleted bone marrow was then injected into the graft recipients. This procedure successfully reduced the incidence of graft-versus-host disease but a new problem soon became evident. Some of the bone marrow recipients rejected the transplant. Their immune system had recognised the marrow as foreign even though the patients had been given drugs before the transplant to suppress their immune responses. Clearly, a better method was needed to suppress the patient’s immune response.

An obvious way to do this was to treat both the donor bone marrow and the transplant recipient with a T-lymphocyte-depleting antibody but the researchers knew that Campath-1M worked poorly in patients so they returned to the laboratory to find another antibody isotype that would be more effective. Their results suggested that an IgG2b antibody was likely to work best. Unfortunately, none of the antibodies produced in the Campath-1 fusion had this isotype. However, monoclonal-antibody-producing cell lines sometimes spontaneously start to make antibodies of a different isotype. So, the researchers painstakingly screened a cell line that was making an IgG2a antibody until they found a cell that had switched to making an IgG2b antibody – Campath-1G. Like the original Campath-1M (and Campath-1H; see below), Campath-1G binds to a molecule called CD52 that is present on lymphocytes and some other human cells.

Campath-1G and Campath-1H go into patients

‘Once we knew we had an antibody that worked in patients, we started to talk to a variety of clinicians who might be interested in using an anti-lymphocyte antibody,’ explains Waldmann. Some of these clinicians were treating patients who had lymphocytic leukaemia, a blood cancer in which lymphocytes replicate uncontrollably. Two patients with this type of cancer were duly treated with Campath-1G and initially responded well although both patients subsequently relapsed. In one patient, their immune system had recognised Campath-1G – a rat antibody – as foreign and destroyed it.

Clearly, a more-nearly human antibody was needed that would be ignored by the human immune system. Fortuitously, another Cambridge scientist, Professor Sir Greg Winter, had just developed a way to ‘humanise’ antibodies. Humanisation is the replacement of some regions in an animal antibody by the equivalent human regions; the animal regions that determine which antigen the antibody recognises are retained in humanised antibodies. Dr Mike Clark, who had joined Waldmann’s laboratory in 1981, started to make a set of fully and partly humanised antibodies from Campath-1G and, together with other team members, tried to determine which human isotypes would work in patients. Campath-1H, a humanised IgG1, was the result of all this basic research although, says Clark, who is now a Reader in Therapeutic Immunology in the Department of Pathology, ̽��ֱ�� of Cambridge, ‘these days, we think that a partly humanised antibody that retained some more of the rat regions would probably have worked just as well.’

Campath-1H was very successful for the treatment of lymphocytic leukaemia and of non-Hodgkin lymphoma (another type of blood cancer), and for use in bone marrow and solid organ transplants. Clinicians also started to use it to treat several autoimmune diseases including vasculitis (inflammation of the blood vessels), rheumatoid arthritis and MS. ̽��ֱ��clinical-grade material needed for these studies was produced in the Therapeutic Antibody Centre (TAC) that Waldmann set up in Cambridge in 1990 with Professor Geoff Hale, a biochemist who had joined Waldmann’s group at the beginning of the Campath-1H story and who is now Visiting Professor of Therapeutic Immunology at the Sir William Dunn School of Pathology, Oxford. ̽��ֱ��TAC moved to Oxford in 1995. ‘Without Geoff’s critical contribution and the support of both Cambridge and Oxford ̽��ֱ��,’ says Waldmann, ‘we would not have been able to initiate many of these studies, including our long-standing collaboration with Alastair Compston in MS.’

Pharmaceutical company involvement

̽��ֱ��development of a drug for clinical use is a highly regulated, long and expensive process, so drugs only get to market if pharmaceutical companies become involved in their development. In the early 1980s, the Cambridge researchers assigned the rights for the Campath-1 cell lines to BTG, originally a government body set up to facilitate the exploitation of inventions from UK academics but now an international specialty pharmaceuticals company. In 1985, BTG licensed Campath-1M to Wellcome Biotech, a subsidiary of the Wellcome Foundation. ‘Many people were very sceptical in the mid-1980s about the commercial future of antibodies and other biotech drugs but Wellcome was excited by the potential of this new area,’ comments Dr Richard Jennings (Director of Technology Transfer and Consultancy Services, Cambridge Enterprise Ltd).

When the basic research being undertaken by Waldmann’s team suggested that Campath-1G and Campath-1H were more likely to have a clinical future than Campath-1M, these antibodies were also licensed to Wellcome Biotech. Indeed, once Campath-1H had been handed over, the company abandoned its work on the earlier antibodies and started a programme of clinical trials of Campath-1H in rheumatoid arthritis, leukaemia and lymphoma. Meanwhile, the academic scientists continued with their basic research, refining and extending their understanding of how Campath-1H was working in various diseases by collaborating closely with the physicians who were giving the antibody to patients. This research was helped along by the development of new molecular techniques and by improved understanding of the human immune system.

Then, in 1995, Wellcome (which merged with Glaxo that year to become Glaxo-Wellcome) decided to abandon its development of Campath-1H, fearing that Campath-1H would not have a billion-dollar market after all. Although the antibody worked well in some types of leukaemia, it did not work in all leukaemias and, in the rheumatoid arthritis trials, Campath-1H had permanently suppressed patients’ immune systems. This decision was very disappointing for Waldmann and his colleagues, who strongly believed in the clinical potential of Campath-1H. ‘We looked at things from a different point of view,’ says Waldmann. ‘As academic scientists, when Campath-1H caused unexpected side effects or did not work as well as expected, our response was to look at the evidence, figure out what had gone wrong, and find ways to put it right rather than giving up.’

In 1997, after protracted negotiations with BTG and Glaxo-Wellcome, LeukoSite Inc. took on the licence to develop Campath-1H. LeukoSite, which merged with Millennium Pharmaceuticals in 1999, partnered with ILEX Oncology to complete the development and obtain US approval in 2001 for Campath-1H to be used for the treatment of B-cell chronic lymphocytic leukaemia (CLL) in patients who had failed to respond to conventional chemotherapy. ̽��ֱ��licence for Campath-1H was then transferred to ILEX Oncology before, finally, in 2004, Genzyme Corporation acquired ILEX Oncology and the production rights to Campath-1H.

Says Mark Enyedy, Senior Vice- President at Genzyme, ‘Campath-1H has had a particularly tortuous commercial history. I think the many changes of commercial support for this product have impeded the realisation of this drug’s commercial potential even though products like this always take an enormous time to develop.’

MS – Campath-1H’s new market?

Last year, the revenue from the use of Campath-1H for the treatment of CLL was around US$100 million but this income may eventually be dwarfed by the revenue generated from the treatment of early relapsing–remitting MS with Campath-1H (the generic name for the drug is alemtuzumab; its registered name is Campath®). As in other diseases, the development of Campath-1H for the treatment of MS has relied on academic researchers willing to do the basic research needed to understand how Campath-1H is working in patients and how to make it more effective.

MS is an inflammatory neurological disease that is caused by damage to myelin, a substance that forms an insulating sheath around the nerve fibres in the central nervous system (CNS; the brain and spinal cord). Electrical messages pass along these nerve fibres to control conscious and unconscious actions. If the myelin sheath is damaged these messages can no longer pass smoothly and quickly between the brain and the body.

Most people with MS are initially diagnosed with relapsing–remitting MS. In this form of the disease, symptoms (which include muscle spasms and stiffness, tremors, bladder and bowel control problems, and pain) occur in episodes that are followed by periods of spontaneous recovery (remissions). Relapses can occur at any time, last for days, weeks or months, and vary in their severity. Most people who have relapsing–remitting MS eventually develop secondary progressive MS in which the occurrence of relapses wanes but overall disability slowly increases.

Early attempts to treat MS

By the late 1980s, it was becoming clear that MS is an autoimmune disease (a disease in which a person’s immune system attacks the person’s own tissues) in which activated T lymphocytes move into the CNS and damage myelin. As Professor Alastair Compston (Professor of Neurology and Head of the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge) explains, ‘we began to wonder whether we could help patients with MS by preventing the movement of activated lymphocytes from the bloodstream into the brain.’ Treatment with Campath-1H looked like one way that this could be achieved and, in 1991, Compston started an 18-year-long collaboration with Waldmann and his team by trying this approach for the first time in a woman who had developed MS some years earlier. ‘At that time, there were no licensed treatments for MS,’ says Compston, ‘and this individual seemed to be facing a particularly grim future. Alarmingly, she actually got much worse for a day or two after receiving Campath-1H but then picked up and remained very well for some years. She even seemed to get back some of her lost functions.’

Keeping in close contact with Waldmann’s team, Compston and colleagues carefully followed the progress of their patient for about 18 months before treating another six people. ‘By 1994, we had satisfied ourselves that Campath-1H treatment could stop the development of new inflammatory lesions in the brain,’ says Compston. In addition, ‘it seemed as though our patients had fewer new attacks after the treatment.’

By 1999, Compston and a clinical trainee, Dr Alasdair Coles, had treated 27 patients, all of whom had already entered the secondary progressive stage of MS. ‘We paused then to analyse our results,’ says Compston. &lsq

uo;We realised that, although we had stopped disease activity in terms of new inflammatory brain lesions and had reduced the number of attacks that people were having, most of our patients were continuing to deteriorate.’ ̽��ֱ��problems that the patients had had when they started Campath-1H treatment were slowly progressing. This observation puzzled the researchers. If MS is an inflammatory autoimmune disease, why was Campath-1H treatment failing to help people in the progressive phase of the disease even though the treatment seemed to turn off inflammation?

̽��ֱ��answer to this conundrum, the researchers realised, is that there are two separate processes going on in MS – inflammation and degeneration. Inflammation causes the attacks in relapsing–remitting MS but also triggers nerve degeneration. Eventually, the degenerative component of the disease gains a momentum of its own and continues even in the absence of inflammation, which results in slow progression and the accumulation of disabilities that don’t get better. ‘Until we used Campath-1H in patients, this separation between inflammation and degeneration was not appreciated,’ says Compston, ‘but its implications were obvious. If this drug was going to be of any use to people with MS, we would have to use it much earlier in the disease process than we had so far.’

Campath-1H for the treatment of relapsing–remitting MS

Compston and Coles now began to treat some of their patients with relapsing–remitting MS with Campath-1H. As before, the treatment almost completely stopped new attacks occurring but, in addition, many of these patients actually began to get better. Their various disabilities began to improve. It was time to take Campath-1H into formal clinical trials to prove the drug’s efficacy and to prepare the way for marketing the drug for the treatment of MS.

With the support of ILEX Oncology (and, from 2004, of Genzyme), a Phase 2 clinical trial was started in December 2002. Patients enrolled into the trial had to meet strict entry criteria and were treated with up to three annual doses of Campath-1H. ̽��ֱ��effects of the drug were measured three years after the initial treatment and, unusually for a Phase 2 trial, its effects were compared with the effects of another drug – interferon beta-1a, the current gold standard treatment for MS. ‘We set the bar high in this trial,’ says Enyedy. ‘Most studies of treatments for MS compare the new treatment with a placebo and only last a year.’ Genzyme, adds Compston, ‘has been fantastically committed to the development of Campath-1H for use in MS.’

̽��ֱ��results of the trial, which were published in 2008 in theNew England Journal of Medicine, showed that there were 70% fewer relapses and that the risk of accumulated disability was 70% lower among the patients receiving Campath-1H than among those treated with interferon beta-1a. Furthermore, as in the patients treated before the trial started, the disability score of patients treated with Campath-1H actually improved; by contrast, it worsened in the patients given interferon beta-1a.

Two large Phase 3 trials are now under way that will finish in 2011. If all goes well, Genzyme expects to apply for marketing approval in 2012, 21 years after the first patient with MS was treated with Campath-1H (and 33 years after Waldmann’s team started the research that produced Campath-1H). ‘So far, ‘ says Compston, ‘we have spent 18 years carefully observing treated patients and learning from our mistakes… With more secure funding for our basic and clinical research in the 1990s, we might have been able to move more quickly. But with a disease like MS, which was then poorly understood, it was always going to take a long while to develop a new drug.’ Importantly, adds Enyedy, ‘if the Phase 3 trials are successful, I think we can stake a claim for a new standard of care for a large subset of patients with relapsing–remitting MS,’ a prospect that, Compston says, is ‘very rewarding for a clinical neurologist who has seen so many young people lose the ability to perform simple aspects of everyday living as a result of this difficult disease.’

Glossary

Antibody: a secreted protein made by the immune system that binds to a specific molecule called its antigen. Antibody binding to an antigen on the surface of pathogens (disease-causing organisms) recruits other parts of the immune system to kill the pathogen. Antibodies are members of a family of proteins called immunoglobulins (Ig).

Antigen: any molecule that can bind specifically to an antibody.

Autoimmune disease: a disease in which the immune system mounts a response against self antigens.

B lymphocyte: a type of white blood cell that makes antibodies.

Bone marrow: the spongy material inside bones where all the cells in the blood, including red blood cells and lymphocytes, are made.

Complement: a set of blood proteins that form one of the immune system’s mechanisms for killing pathogens.

Isotypes: different classes of immunoglobulins such as IgG and IgM. Some of the isotypes have subclasses. For example, there are four human IgG subclasses – IgG1, IgG2, IgG3 and IgG4.

Monoclonal antibodies: antibodies that are made artificially in the laboratory.

Self antigens: molecules that are in an individual’s own tissues.

T lymphocytes: a type of white blood cell that helps B lymphocytes make antibodies and that also directly kills pathogen-infected cells.

Tolerance: the failure to respond to an antigen. ̽��ֱ��immune system is usually tolerant to self antigens.

̽��ֱ��path from innovation to impact can be long and complex. Here we describe the 30-year journey behind the development of a drug now being used to treat multiple sclerosis.

As in other diseases, the development of Campath-1H for the treatment of MS has relied on academic researchers willing to do the basic research needed to understand how Campath-1H is working in patients and how to make it more effective.

Photograph: Greg Smolonski

Waldmann, Clark and Hale

A tale of two innovations

We are often taken aback by the sudden appearance of a new innovation that has clear economic or clinical impact. Just how did these innovations arise?

Academic scientists working in universities are driven to do their research for many reasons. Some see their research as a way to develop new drugs or to build more powerful computers, for example. Many academic scientists, however, are simply curious about the world around them. They may want to understand the intricacies of the immune system or how the physical structure of a material determines its properties at a purely intellectual level. They may never intend to make any practical use of the knowledge that they glean from their studies.

Importantly, however, even the most basic, most fundamental research can be the starting point for the development of materials and technologies that make a real difference to the everyday life of ordinary people and that bring economic benefit to the country. Indeed, said Dr Richard Jennings, Director of Technology Transfer and Consultancy Services at Cambridge Enterprise Ltd, ̽��ֱ�� of Cambridge, ‘what universities are good at is fundamental research and it is high-quality basic research that generates the really exciting ideas that are going to change the world.’

But it takes a great deal of time, money and commitment to progress from a piece of basic research to a commercial product, and the complex journey from the laboratory to the marketplace can succeed only if there is long-term governmental support for the academic scientists and their ideas as well as the involvement of committed commercial partners and well-funded technology transfer offices.

Two particular stories illustrate the long and complex path taken from the laboratory to commercial success by two very different ̽��ֱ�� of Cambridge innovations. In the case of Plastic Logic, basic research on materials called organic semiconductors that started in the 1980s and that continues today has led to the development of a new type of electronic reader that should be marketed in early 2010 and, more generally, to the development of ‘plastic electronics’, a radical innovation that could eventually parallel silicon-based electronics. For Campath, the journey started just before Christmas in 1979 in a laboratory where researchers were trying to understand an immunological concept called tolerance. Now, nearly three decades later and after a considerable amount of both basic research and commercial development, Campath-1H is in Phase 3 clinical trials for the treatment of relapsing–remitting multiple sclerosis.

‘Both innovations are likely to have profound impacts over the next two years and it is important to recognise the deep temporal roots of both,’ said Professor Ian Leslie, Pro-Vice-Chancellor for Research.

Professor Leslie highlighted that an important lesson to draw from these stories ‘is the need for universities and other recipients of public research funding to implement and develop processes to support the translation of discovery to impact or, more generally, to develop environments in which the results of discovery can be taken forward and in which external opportunities for innovation are understood.’

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Plastic Logic: from innovation to impact

bjb42 — Sat, 01 Aug 2009 00:00:00 +0000

̽��ֱ��path from innovation to impact can be long and complex. Here we describe the fascinating story behind the development of a new type of electronic reader.

̽��ֱ��story of Plastic Logic started in the mid-1980s when Professor Sir Richard Friend – then a lecturer in the Department of Physics at the ̽��ֱ�� of Cambridge – began to work on organic semiconductors [see Glossary below]. ‘My interest was pure curiosity,’ says Friend, who is now the Cavendish Professor of Physics at the ̽��ֱ�� of Cambridge. He was interested, he explains, in gaining a basic understanding of how electrons might be made to move in carbon-based semiconductors, rather than being driven by the prospect that his research might be commercially useful.

Semiconductors – materials that conduct electricity under some conditions but not others – are used to make the integrated circuits that run computers and other electronic devices. Silicon is the best known semiconductor but, in the 1960s, researchers discovered that some organic molecules also behave as semiconductors. Specifically, small molecules that contain carbon atoms linked by alternating single and double bonds – so-called conjugated molecules – behave as semiconductors because some of their electrons are delocalised and ‘shared’ throughout the molecule. Friend wanted to know whether polymers made from building blocks of conjugated molecules would also behave as semiconductors. ‘We were interested in this type of molecule because we thought that, if they did behave as semiconductors, we might be able to use them to make electronic devices simply by dissolving the polymers in a solvent and then painting them onto a surface,’ says Friend.

By 1988, Friend’s research group had managed to make a transistor from the conjugated polymer polyacetylene. But, notes Professor Henning Sirringhaus, Hitachi Professor at the ̽��ֱ�� of Cambridge and Friend’s colleague since 1997, ‘the performance of this polymer or plastic transistor was very poor because the speed at which electrons and holes move through polyacetylene – a property called mobility – is much lower than in silicon. Plastic transistors were pretty much a scientific curiosity at that point, although they did provide a useful device for studying the electrical properties of new materials.’

A serendipitous discovery

Friend’s team now started to investigate whether better transistors could be made from other conjugated polymers. ‘We thought that a poorly studied compound called poly(p-phenylene vinylene), PPV, looked promising,’ says Friend, ‘and we began a collaboration with Andrew Holmes, a natural products scientist then working in the Department of Chemistry in Cambridge, to make PPV and to use it to make transistors.’

Unfortunately, PPV was not ideal for transistors – it was too good an insulator. But rather than giving up on PPV, the researchers decided to measure its insulating properties. ‘Instead of making a parallel electrode arrangement as we do for transistors, in February 1989 we made a stacked electrode arrangement as we do in diodes and sandwiched the PPV between the two electrodes to measure its insulating abilities,’ explains Friend.

By good fortune, Dr Jeremy Burroughes, who had made the first polyacetylene transistors while a PhD student in Friend’s laboratory, used a thin, semi-transparent layer of aluminium to make the top electrode in this PPV-containing device. When Burroughes (who is now the Chief Technology Officer at Cambridge Display Technology, CDT) applied a voltage to the device, he unexpectedly saw green light coming through the electrode. Friend immediately contacted Dr Richard Jennings (Director of Technology Transfer and Consultancy Services, Cambridge Enterprise Ltd) in what was then the ̽��ֱ��’s industrial liaison office to tell him about the strange, light-emitting piece of plastic and to ask for advice on patenting this discovery.

‘As soon as Richard explained what he had seen, we began to think about applications,’ says Jennings. ‘Plastic light-emitting displays, light-emitting clothing, plastic TV screens – it didn’t take much imagination to see how these polymer light-emitting diodes [P-LEDs] might be used and my advice was to patent the invention immediately.’ A particular appeal of light-emitting plastics, say both Friend and Jennings, was that these materials could be solution-processed or painted over a large area, a much simpler process than that needed to make liquid crystal displays (LCDs), the up-and-coming display technology in the late 1980s.

Patents for P-LEDs were filed in April 1989 and April 1990. Then, in October 1990, the researchers published a letter in the journalNatureentitled ‘Light-emitting diodes based on conjugated polymers’. ‘ ̽��ֱ��rest of the world simply dived in after we published. We had scores of imitators and our patent was challenged on several occasions,’ says Friend.

But, despite the academic interest in P-LEDs, Friend failed to find a UK electronics company to license and develop the invention. ‘It wasn’t that the companies weren’t willing to license the patent,’ stresses Friend. ‘It was more that they did not see organic light-emitting diodes as a core business and I was concerned that they would simply sit on our idea and not do the work needed to develop it. ̽��ֱ��quickest single way to kill a good idea is to put it into the wrong hands,’ comments Friend.

So, in 1992, Friend, with help from the ̽��ֱ�� of Cambridge and local seed venture capital, founded CDT. Although the original intention was that CDT would be a materials manufacturing company, CDT has concentrated on developing new technologies and licensing them to other companies. For example, in association with various industrial partners, CDT has developed a method to make P-LED displays using inkjet printing, thin-film transistors to stimulate the P-LED-containing pixels in displays, and polymers that emit red or blue light when stimulated instead of green light. In 2004, CDT was floated on the NASDAQ National Market and, in 2007, it was acquired by the Sumitomo Chemical Company, which maintains substantial R&D activity in and around Cambridge.

Importantly, says Friend, a strong symbiotic relationship has developed between CDT and the scientists working in the ̽��ֱ��: ‘Over the years, we have sent a lot of ideas to CDT but in return we have had access to the materials and methods that CDT has developed and this has helped us to push our fundamental research along much faster than would have been possible if we had had to do everything in the ̽��ֱ��.’

Back to transistors

While P-LEDs were being developed, some work continued in Cambridge and elsewhere on plastic transistors. Because silicon-based transistors were so good, explains Sirringhaus, ‘there wasn’t any commercial drive to work on plastic transistors and probably fewer than ten groups worldwide were working on the problem.’ Adds Friend, ‘it was really a matter of waiting for new materials to be made, waiting for the technology and science to develop to a stage where we could take the transistors forward.’

Then, in 1997, a way was found to increase the mobility of polymer semiconductors. ̽��ֱ��problem with the original polymer semiconductors had been that the long-chain molecules within these substances were disordered – ‘like a bowl of spaghetti’, says Sirringhaus. As the charge moved through this disordered mass, it encountered configurations where it didn’t know where to go and this reduced the material’s mobility. ̽��ֱ��polymer chains were disordered because, to process polymer solutions,

flexible side chains have to be attached to the polymer chains. Unfortunately, these side chains made the polymer disordered and electrically poorly conducting. ̽��ֱ��1997 breakthrough was the discovery of a way to deposit materials from polymer solutions that consist of alternating layers of conjugated polymers lying in a plane and insulating side chains. ‘ ̽��ֱ��mobility in the conjugated plane can be very high and it doesn’t matter about the mobility elsewhere in the structure,’ explains Sirringhaus.

Although the demonstration that the mobility of polymer semiconductors could rival that of inorganic semiconductors like silicon was important, before the researchers could persuade large companies or venture capitalists to invest time and/or money in their discovery, they still had to show that their new material could be used to make transistors in a practical manner.

‘At that time, we were developing methods to use inkjet printing to deposit P-LEDs onto substrates so we started to investigate whether the same process could be used to print transistors,’ says Sirringhaus. Within a few months, Sirringhaus and PhD student Takeo Kawase, on secondment from Seiko Epson, had printed a few transistors onto small substrate chips and had shown that these simple circuits performed reasonably well. ‘We now had a credible story on the materials and a credible way to make devices from them so we began to think about commercialisation,’ says Sirringhaus. Indeed, says Friend, ‘I had a strong sense that the future seminal events in the development of organic transistors were going to be engineering events, not science events, and I believed that these were most likely to happen in a well-focused industrial environment.’

Plastic Logic is founded

With this in mind, the researchers approached the entrepreneur and venture capitalist Dr Hermann Hauser, a co-founder of Amadeus Capital Partners (Cambridge) and an early investor in CDT, to see whether he would invest money in the commercial development of organic polymer transistors.

‘I remember visiting Richard and his group in the Cavendish,’ says Hauser. ‘They only had a few transistors working at this time [1998] and when they stopped working they prodded them with toothpicks!’ Luckily, Hauser, with his background in physics and interest in electronics, instantly recognised that Friend, Sirringhaus and their colleagues had made a very fundamental breakthrough and, with his help, Plastic Logic was formed in January 2000.

What is so special about plastic transistors?

When Plastic Logic started, all the electronic displays in the world were made on glass. Displays like those attached to computers contain millions of pixels, each of which is switched on and off by an individual silicon transistor. To produce these transistors, amorphous (non-crystalline) silicon is processed at high temperatures. Consequently, silicon-based transistors can only be produced on a substrate like glass that can withstand high temperatures; a plastic substrate would melt or deform. But displays that contain glass are heavy, rigid and fragile and unsuitable for use in anything but very small mobile displays. ̽��ֱ��production of plastic transistors, by contrast, does not require high temperatures so they can be laid down on plastic substrates that are much lighter, and more flexible and robust than glass. This means that large portable displays can be made by using plastic instead of silicon transistors.

Plastic transistors have a second advantage over silicon transistors when it comes to making large displays. Electronic circuits contain many layers that have to be accurately aligned with each other. In a large display, the dimensions of the substrate inevitably change slightly during the production process. Silicon-based displays are made using a lithographic process in which patterns are sequentially deposited onto substrates using metal masks. Unfortunately, any small changes in the dimensions of the substrate during the production process mean that the masks do not line up accurately and the resultant display is defective. With displays that contain plastic transistors, computers drive the inkjet printers that make the various layers of the device so it is possible to allow for changes in the substrate’s dimensions.

From single transistors to an electronic reader

‘When Plastic Logic was founded,’ says Jennings, ‘there wasn’t a clear business plan but Hermann Hauser was a very far-sighted investor who, knowing the track record of Richard Friend and Henning Sirringhaus, was willing to put money into their company to see where it would go.’ Over the next few years, Plastic Logic raised considerable sums of money to support its work and by 2006 it had developed its plastic transistor technology sufficiently to produce a display containing a million transistors. It had also developed an application for these displays – a plastic electronic reader. Since 2006, Plastic Logic has raised more than US$100 million to build a large manufacturing plant in Dresden (Germany); its research and development department still remains in Cambridge but its corporate headquarters is now based in Mountain View (California, USA). Trials of the electronic reader with key customers should be completed by the end of 2009 and commercial production will be rolled out in 2010.

̽��ֱ��electronic reader, which has an A4 screen that is about as heavy and thick as a sheet of paper, uses an ‘active matrix display’, an array of pixels in which each pixel contains minute plastic capsules filled with a liquid that contains black and white particles. These particles have different charges so that when an electric current is applied to a pixel, either the white or the black particles move to the front of the capsule and the pixel appears white or black. A plastic transistor behind each pixel applies the electric charges and the whole device is printed onto a thin, flexible sheet of plastic.

Plastic Logic’s electronic reader will enable users to read their own documents anywhere and will give them access to newspapers and books and, according to Friend, Sirringhaus and Hauser, it has several advantages over existing electronic readers such as Amazon’s Kindle. Its display is lighter and more robust than the glass-based displays in other readers and, because the display is bigger than those in other readers, it is more suitable for accessing newspapers. Also, the device uses very little energy because, unlike other readers, the display in the Plastic Logic reader does not need a back light. Consequently, once a page is set, it can remain in place without consuming any energy. Thus, users should be able to take a Plastic Logic reader away on holiday, for example, without having to take a battery charger.

Other hopes for plastic electronics – the need for continuing basic research

Plastic Logic should produce several hundred thousand electronic readers in 2010 and, in later years, it could be producing millions of units. But Hauser believes that plastic electronics will have much broader applications in the future. While Plastic Logic was developing its electronic reader, he explains, basic research was continuing in the ̽��ֱ�� of Cambridge, where Sirringhaus’ group recently made an important breakthrough by discovering how to make a CMOS plastic transistor.

‘CMOS’ stands for complementary metal oxide semiconductor, a type of semiconductor that can be used to produce a combined n-type and p-type transistor. This type of transistor is needed to build complex devices like computer processors but for many years it seemed that it would be impossible to build plastic transistors with the properties of CMOS transistors – polymer semiconductors were all p-type semiconductors because they all carried current in the form of holes. Then, in 2005, Sirringhaus and his colleagues showed that the reason why th

ere were no n-type polymer semiconductors was because the electrons were being trapped at the interface between the semiconductor and adjacent insulators. By studying this interface, the researchers were able to produce an n-type polymer semiconductor, which opened up the possibility of designing the CMOS circuits that are necessary for the development of a broad plastic electronics industry.

However, Friend, Sirringhaus and Hauser stress that relatively little is known about polymer semiconductors and, because these materials are so different from silicon, it is not possible to rely on established semiconductor physics to understand how they work. Thus, it is essential that fundamental research on polymer semiconductors continues to be funded within UK universities. This, together with improved governmental support for the companies involved in plastic electronics, should ensure that the UK’s current lead in the field of plastic electronics is retained and that the UK reaps the financial rewards of the groundbreaking, curiosity-driven basic research in which Friend, Sirringhaus and their colleagues excel.

Glossary

Conductor:a material that can carry an electric current.

Diode:an electronic component with two electrodes that conducts electric current in only one direction.

Insulator:a non-conductor of electric current.

Light-emitting diode (LED):a diode that emits light when current passes through it. LEDs are used in many electronic devices.

Liquid crystal display (LCD):a display technology in which a current passing through a liquid crystal solution makes the crystals line up so that light cannot pass through them.

Organic semiconductor:a carbon-based semiconductor.

Pixels:picture elements, the units from which images are made on televisions and computer monitors.

Plastic (or polymer) semiconductor:a semiconductor made from an organic polymer.

Plastic (or polymer) transistor:a transistor that contains a plastic semiconductor.

Semiconductor:a substance that conducts electricity only under some conditions. ̽��ֱ��conductivity of semiconductors can be increased by applying heat, light or a voltage. Ann-typesemiconductor carries current mainly in the form of negatively charged electrons. Ap-typesemiconductor carries current mainly as electron deficiencies calledholes; a hole has an equal and opposite electric charge to an electron.

Transistor:a semiconductor device used to amplify or switch electronic signals. A small current across one pair of terminals in a transistor controls the current at another pair of terminals, either amplifying the original current or turning the current on and off in a circuit.

̽��ֱ��path from innovation to impact can be long and complex. Here we describe the fascinating story behind the development of a new type of electronic reader.

‘Plastic light-emitting displays, light-emitting clothing, plastic TV screens – it didn’t take much imagination to see how these polymer light-emitting diodes might be used and my advice was to patent the invention immediately.’

Dr Richard Jennings

Plastic Logic

Electronic reader

A tale of two innovations

We are often taken aback by the sudden appearance of a new innovation that has clear economic or clinical impact. Just how did these innovations arise?

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

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