In February 1989, Jeremy Burroughes, at that time a postdoc in the research group of Richard Friend and Donal Bradley at Cambridge, noticed that a diode structure he’d made from the semiconducting polymer PPV glowed when a current was passed through it. This wasn’t the first time that interesting optoelectronic properties had been observed in an organic semiconductor, but it’s fair to say that it was the resulting Nature paper, which has now been cited more than 8000 times, that really launched the field of organic electronics. The company that they founded to exploit this discovery, Cambridge Display Technology, was floated on the NASDAQ in 2004 at a valuation of $230 million. Now organic electronics is becoming mainstream; a popular mobile phone, the Samsung Galaxy S, has an organic light emitting diode screen, and further mass market products are expected in the next few years. But these products will be made in factories in Japan, Korea and Taiwan; Cambridge Display Technology is now a wholly owned subsidiary of the Japanese chemical company Sumitomo. How is it that despite an apparently insurmountable academic lead in the field, and a successful history of University spin-outs, that the UK is likely to end up at best a peripheral player in this new industry? (more…)
Archive for the ‘Nanobusiness’ Category
The Oxford University spin-out Oxford Nanopore Technologies created a stir last month by announcing that it would be bringing to market this year systems to read out the sequence of individual DNA molecules by threading them through nanopores. It’s claimed that this will allow a complete human genome to be sequenced in about 15 minutes for a few thousand dollars; the company also is introducing a cheap, disposable sequencer which will sell for less that $900. Speculation has now begun about the future of the company, with valuations of $1-2 billion dollars being discussed if they decide to take the company public in the next 18 months.
It’s taken a while for this idea of sequencing a single DNA molecule by directly reading out its bases to come to fruition. The original idea came from David Deamer and Harvard’s Dan Branton in the mid-1990s; from Hagen Bayley, in Oxford, came the idea of using an engineered derivative of a natural pore-forming protein to form the hole through which the DNA is threaded. I’ve previously reported progress towards this goal here, in 2005, and in more detail here, in 2007. The Oxford Nanopore announcement gives us some clues as to the key developments since then. The working system uses a polymer membrane, rather than a lipid bilayer, to carry the pore array, which undoubtedly makes the system much more robust. The pore is still created from a pore forming protein, though this has been genetically engineered to give greater discrimination between different combinations of bases as the DNA is threaded through the hole. And, perhaps most importantly, an enzyme is used to grab DNA molecules from solution and feed them through the pore. In practise, the system will be sold as a set of modular units containing the electronics and interface, together with consumables cartridges, presumably including the nanopore arrays and the enzymes. The idea is to take single molecule analysis beyond DNA to include RNA and proteins, as well as various small molecules, with a different cartridge being available for each type of experiment. This will depend on the success of their program to develop a whole family of different pores able to discriminate between different types of molecules.
What will the impact of this development be, if everything works as well as is being suggested? (The prudent commentator should stress the if here, as we haven’t yet seen any independent trials of the technology). Much has already been written about the implications of cheap – less than $1000 – sequencing of the human genome, but I can’t help wondering whether this may not actually be the big story here. And in any case, that goal may end being reached with or without Oxford Nanopore, as this recent Nature News article makes clear. We still don’t know whether the Oxford Nanopore technique will be yet competitive on accuracy and price with the other contending approaches. I wonder, though, whether we are seeing here something from the classic playbook for a disruptive innovation. The $900 device in particular looks like it’s intended to create new markets for cheap, quick and dirty sequencing, to provide an income stream while the technology is improved further – with better, more selective pores and better membranes (inevitably, perhaps, Branton’s group at Harvard reported using graphene membranes for threading DNA in Nature last year). As computers continue to get faster, cheaper and more powerful, the technology will automatically benefit from these advances too – fragmentary and perhaps imperfect sequence information has much greater value in the context of vast existing sequence libraries and the data processing power to use them. Perhaps applications for this will be found in forensic and environmental science, diagnostics, microbiology and synthetic biology. The emphasis on molecules other than DNA is interesting too; single molecule identification and sequencing of RNA opens up the possibility of rapidly identifying what genes are being transcribed in a cell at a given moment (the so-called “transcriptome”).
The impact on the investment markets for nanotechnology is likely to be substantial. Existing commercialisation efforts around nanotechnology have been disappointing so far, but a company success on the scale now being talked about would undoubtedly attract more money into the area – perhaps it might also persuade some of the companies currently sitting on huge piles of cash that they might usefully invest some of this in a little more research and development. What’s significant about Oxford Nanopore is that it is operating in a sweet spot between the mundane and the far-fetched. It’s not a nanomaterials company, essentially competing in relatively low margin speciality chemicals, nor is it trying to make a nanofactory or nanoscale submarine or one of the other more radical visions of the nanofuturists. Instead, it’s using the lessons of biology – and indeed some of the components of molecular biology – to create a functional device that operates on the true single molecule level to fill real market needs. It also seems to be displaying a commendable determination to capture all the value of its inventions, rather than licensing its IP to other, bigger companies.
Finally, not the least of the impacts of a commercial and technological success on the scale being talked about would be on nanotechnology itself as a discipline. In the last few years the field’s early excitement has been diluted by a sense of unfulfilled promise, especially, perhaps, in the UK; last year I asked “Why has the UK given up on nanotechnology?” Perhaps it will turn out that some of that disillusionment was premature.
I spent yesterday at a meeting at the Institute of Mechanical Engineers, Nanotechnology in Medicine and Biotechnology, which raised the question of what is the right size for new interventions in medicine. There’s an argument that, since the basic operations of cell biology take place on the nano-scale, that’s fundamentally the right scale for intervening in biology. On the other hand, given that many current medical interventions are very macroscopic, operating on the micro-scale may already offer compelling advantages.
A talk from Glasgow University’s Jon Cooper gave some nice examples illustrating this. His title was Integrating nanosensors with lab-on-a-chip for biological sensing in health technologies, and he began with some true nanotechnology. This involved a combination of fluid handling systems for very small volumes with nanostructured surfaces, with the aim of detecting single biomolecules. This depends on a remarkable effect known as surface enhanced Raman scattering. Raman scattering is a type of spectroscopy that can detect chemical groups with what is normally rather low sensitivity. But if one illuminates metals with very sharp asperities, this hugely magnifies the light field very close to the surface, increasing sensitivity by a factor of ten million or so. Systems based on this effect, using silver nanoparticles coated so that pathogens like anthrax will stick to them, are already in commercial use. But Cooper’s group uses, not free nano-particles, but very precisely structured nanosurfaces. Using electron beam lithography his group creates silver split-ring resonators – horseshoe shapes about 160 nm across. With a very small gap one can get field enhancements of a factor of one hundred billion, and it’s this that brings single molecule detection into prospect.
On a larger scale, Cooper described systems to probe the response of single cells – his example involved using a single heart cell (a cardiomyocyte) to screen responses to potential heart drugs. This involved a pico-litre scale microchamber adjacent to an array of micron size thermocouples, which allow one to monitor the metabolism of the cell as it responds to a drug candidate. His final example was on the millimeter scale, though its sensors incorporated nanotechnology at some level. This was a wireless device incorporating an electrochemical blood sensor – the idea was that one would swallow this to screen for early signs of bowel cancer. Here’s an example where, obviously, smaller would be better, but how small does one need to go?
A couple of pieces in the Financial Times today and yesterday offer some food for thought about the problems of commercialising scientific research. Yesterday’s piece – Drug research needs serendipity (free registration may be required) – concentrates on the pharmaceutical sector, but its observations are more widely applicable. Musing on the current problems of big pharma, with their dwindling pipelines of new drugs, David Shaywitz and Nassim Taleb (author of The Black Swan), identify the problem as a failure to deal with uncertainty; “academic researchers underestimated the fragility of their scientific knowledge while pharmaceuticals executives overestimated their ability to domesticate scientific research.”
They identify two types of uncertainty; there’s the negative uncertainty of all the things that can go wrong as one tries to move from medical research to treatments. Underlying this is the simple fact that we know much less about human biology, in all its complexity, than one might think from all the positive headlines and press releases. It’s in response to this negative uncertainty that managers have attempted to impose more structure and focus to make the outcome of research more predictable. But why this is generally in vain? “Answer: spreadsheets are easy; science is hard.” According to Shaywitz and Taleb, this approach isn’t just doomed to fail on its on terms, it’s positively counterproductive. This is because it doesn’t leave any room for another type of uncertainty: the positive uncertainty of unexpected discoveries and happy accidents.
Their solution is to embrace the trend we’re already seeing, for big Pharma to outsource more and more of its functions, lowering the barriers to entry and leaving room for “a lean, agile organisation able to capture, consider and rapidly develop the best scientific ideas in a wide range of disease areas and aggressively guide these towards the clinic.”
But how are things for the small and agile companies that are going to be driving innovation in this new environment? Not great, says Jonathan Guthrie in today’s FT, but nonetheless “There is hope yet for science park toilers”. The article considers, from a UK perspective, the problems small technology companies are having raising money from venture capitalists. It starts from the position that the problem isn’t shortage of money but shortage of good ideas; perhaps not the end of the age of innovation, but a temporary lull after the excitement of personal computers, the internet and mobile phones. And, for the part of the problem that lies with venture capitalists, misreading this cycle has contributed to their difficulties. In the wake of the technology bubble, venture capital returns aren’t a good advertisement for would-be investors at the moment – “funds set up after 1996 have typically lost 1.4 per cent a year over five years and 1.8 per cent over 10 years, says the British Private Equity and Venture Capital Association.” All is not lost, Guthrie thinks – as the memory of the dotbomb debacles fade the spectacular returns enjoyed by the most successful technology start-ups will attract money back into the sector. Where will the advances take place? Not in nanotechnology, at least in the form of the nanomaterials sector as it has been understood up to now: “materials scientists have engineered a UK nanotechnology sector so tiny it is virtually invisible.” Instead Guthrie points to renewable energy and power saving systems.