The IBM device would read single strands of DNA as they passed through layers of a microchip.

Sequencing your genome is going to be such big business that everyone wants to get in on it, even if they aren’t ready. In a recent press release, IBM announced that it is working to create a microchip that will sequence DNA by running it through tiny ‘nanopores’. The DNA Transistor will be able to sequence the entire genome rapidly and for less than $1000. While a working prototype of the chip won’t be created for three more years, IBM thinks that the theory and computation behind the concept is sound. If ultimately successful, the computer giant would launch itself to the forefront of the genome sequencing field. For now though, the company is just pushing an idea, not a product. I love it when companies compete in a field, but IBM’s got years of hard work before it could be a genome sequencing competitor. A fact that makes their press release seem premature at best. Still, you should check out the admittedly cool PR video after the break.

The first human genome cost around three billion dollars to sequence. Today, Illumina is offering to do the same for $50,000 and Complete Genomics is looking to a $5000 price tag under certain conditions by the end of next year. But the big hurdle is $1000. At that point, sequencing a genome will become accessible to almost anyone, and could see wide spread adoption in health and medicine. Using genetic information, doctors could provide personalized health care that would target illnesses and choose treatments which best suit your body. Knowing more, we could live much longer.


IBM’s proposed device would work by threading a single strand of DNA through a 3 nanometer diameter pore that is drilled through a silicon chip using an electron beam. As the press release admits, that idea is being explored by several companies around the world (including Agilent, Sequenom, NabSys, and Oxford Nanopore Technologies). The IBM innovation is to slow the progress of the DNA through the nanopore by using electric fields as gates. By controlling the speed at which the DNA moves, IBM hopes to read the strand. That reading would be accomplished by measuring the variation in electric potentials across the pore, which is uniquely different depending on if the base is A, C, T, or G.

Strands of DNA suspended in a solvent would be encouraged to pass through the nanopore due to an electric bias. Electric fields in the pore would control strand movement and read the DNA.

When I first looked at the IBM video describing the DNA Transistor, I thought, “I’ve seen this before.” I interviewed DNA Electronics CEO Christopher Toumazou about the combination of CMOS technology and genetics last month. The SNP Dr is a hand held silicon chip based device that reads DNA to find interesting genetic sequences. Unlike IBM’s device, it’s already been made and tested.

But there are big differences between the two devices besides the fact that IBM’s is still on the drawing board. First, the SNP Dr looks for single nucleotide polymorphisms, the single gene variations that have important impact on physical traits, drug reactions, etc. The SNP Dr does not sequence your entire genome as the DNA Transistor plans to do. If it helps to draw comparisons to companies, the SNP Dr is like 23andMe and the DNA Transistor is more like Illumina or Complete Genomics. Secondly, the SNP Dr works by using enzymes (polymerases) to cause protons to be released as a strand of DNA is read, and the silicon chip measures that current. The DNA Transistor would only use electric fields to read the strand as it passes through the nanopore.

So the DNA Transistor could be an important improvement over the existing SNP Dr technology, but not yet. In fact, IBM is looking to have a working prototype in three years. That seems like forever. Complete Genomics will have $5000 sequencing by the end of 2010 and it should only get cheaper thereafter. The same goes for Illumina and every other genome focused company. By 2013, the $1000 hurdle could have been jumped by one of these companies. Heck, by that time, we could see the price drop much lower. If the DNA transistor is to be competitive that far down the road it will have to be cheaper (IBM has tossed around the $100 mark as a possibility) or much much faster.

Luckily for IBM, silicon technology has speed down to a fine science. I don’t know if the DNA Transistor is going to be the device that defines the next generation of DNA sequencing, but I do know that the marriage of CMOS and genetics is powerful. That’s a sentiment shared by the researchers behind the IBM device, Stas Polonsky and Gustavo Stolovitzky, in the companion video embedded below.

Everything about this press release strikes me as hype. Good hype, sincere hype, but hype all the same. There’s no doubt that the combination of genome sequencing and microchip technology is a game changing idea, but IBM doesn’t have a monopoly on it. Obviously DNA Electronics has a somewhat related device already nearing market, and there are other companies also working towards using nanopores to sequence the whole genome. A lot can happen in three years. Hopefully someone will have a working prototype by that time. It could be IBM, but no matter who it is, their cheap and quick sequencing is going to change our lives.

DNA Electronics' SNP Dr. will allow you to find important genes in your DNA in less than 30 minutes.

If your computer and your DNA had a baby, it would be the SNP Dr. from DNA Electronics. SNP Dr. is the world’s first hand held semi-conductor device that will be able to read your DNA in about 15-30 minutes. I was able to chat with DNA Electronics CEO Prof. Chris Toumazou who is also the founder of Toumaz Technologies, the company that brought you Sensium. Toumazou let me in on how SNP Dr. will change medicine and genetic testing, and what we can look forward to in the future of semi-conductors and biology.

The current means of looking at your genetic code involves actual looking. Optic sensors help to pour through your DNA and discover variations. That technique is slow and difficult to scale down. Semiconductors, though, are getting faster and smaller every day. So a semiconductor device like SNP Dr. can be cheap and easily produced at a hand held size. Imagine a world where genetic testing could be done with just some spit, a cotton swab, and your iPhone.

A single nucleotide polymorphism or SNP (pronounced ‘snip’) is an interesting single-gene variation in your DNA. Geneticists have discovered hundreds, many of which can indicate proclivities to disease, physical traits, or negative reactions to medicines. Companies like 23andMe can test your DNA to see which SNPs you have. The SNP Dr, still in early prototyping, has a semi-conductor processor (a ‘SNP chip’) that reads your DNA by looking for a SNP. Which SNP? Depends on what you need to do. Are you a doctor trying to make sure you can proscribe someone a medicine without it killing them? Soldier checking for biological weapons? Farmer trying to figure out which seeds you should plant to avoid parasitic infestation? DNA Electronics could develop a SNP chip for any of the above.

Making semiconductors and biology play nice

Prof. Toumazou’s background is in semiconductor design and engineering. He developed the ultra low power technology for IT applications that was adapted into medical sensing devices like Sensium. While working with a group trying to develop a cochlear implant, Toumazou started to realize that, “biology doesn’t need the higher precision of digital processing…The [modern] world is digital, but human space is analog.” Analog signals and processing mean lower power consumption and tinier devices.

But analog signals drift, which is problematic when you want to measure chemicals in body fluids like potassium, glucose, or urea (all one time projects of Toumazou). So what signal in your body doesn’t drift? The one that’s got all the important information anyway: your DNA.

With specialized molecules (polymerases) you can get reactions with DNA that release protons. That’s an electrical signal you can track with semiconductor technology. Get the right kind of reactions going, and you can detect all the changes in DNA. Find when base pairs switch and you can start reading your genetic code just by measuring changes in electrical signals. It’s like deciphering Morse Code when there is just four letters in the alphabet (GTCA). SNP Dr. represents one of the world’s first looks at combining DNA logic with CMOS technology.

So can I buy one today?

Semiconductor technology is well explored and well understood, so it’s no surprise that the semiconductor side of SNP Dr. is well underway. When the UK launched its Life Science Blueprint initiative to strengthen government support of biotech in Britain, guess what they got to see at the labs of Imperial College? Check out the prototype version of SNP Dr in the video below (0:28). Yep, that’s Prime Minister Gordon Brown and Lord Drayson.

The current SNP Dr. prototype can actively demonstrate a number of SNPs on a single chip, but there’s still a good deal of work to be done for a cotton swab of spit to interface with information technology. Toumazou says that they are already working with Pfizer, and other pharmaceutical companies on predicting drug responses in patients.

Prof. Toumazou is confident SNP Dr products can be developed and launched fairly quickly. Unregulated uses of DNA testing (such as having 23andMe looking at your genetic traits) could start adopting SNP Dr within the next 1-2yrs. Genomic studies, drug responses, and infection detection are all highly regulated, rightfully so, and will take a little longer to approve the new technology. According to Toumazou, These more rigorous uses of SNP Dr. will probably be seen in 2-5 years.

A SNP Dr. in every home

CTO Dr. Leila Shepherd works to bring SNP Dr to market.

In terms of the overall business model, integrating genetics and semiconductor chips is still a very new field and a number of opportunities may emerge, from selling the handheld SNP Dr, to producing new and updated disposable SNP chips on a regular basis. But no matter where the most revenue may lie for DNA Electronics, you can bet they are going to make a big impact. For a couple of hundred dollars, almost any professional could buy a SNP Dr, a whole bag of SNP chips and get to testing. Doctors, farmers, soldiers, forensic scientists, cosmetic counter artists, personal trainers, or just the interested layman could suddenly test themselves and others for important genetic traits. Some of that activity is bound to be regulated, but it still leaves plenty of room for the SNP Dr. to find its place in the world.

It may be a very important place. With the ability to create new SNP chips at the rate of current silicon technologies (ask Intel how fast that is) we could see SNP Dr. become a rapid response tool in the fight against biological threats. Terrorist weapons? Sure, but think about infectious diseases like swine flu, blights on crops, or allergies to medicines. If scientists can find a SNP, DNA electronics can build a SNP chip for it. “Anything that has a defined sequence,” says Toumazou, is fair game. After all, “it’s not discovery, it’s matching.”

In fact, concentrating on matching doesn’t just make SNP Dr. fast and reliable, it also makes it a logician. Toumazou says that SNP chips could be geared towards boolean logic. Does this organism have gene X AND gene Y? That enhances the applications we’ve already discussed and makes the technology a boon to synthetic biology. Anything a scientist can define a sequence for, DNA Electronics can help them detect in minutes. Genetic engineers will be able to search and sort their creations for traits nearly in real time. That’s going to lead to some amazing developments.

An ounce of prevention

As I’ve said before, Toumazou is also the brains behind Sensium which will help health monitoring. Along with SNP Dr, we start to see a clear trend: the more you know, the healthier you can live. Toumazou is working to “change healthcare in the future, if you want to call it healthcare.” Maybe the new paradigm is lifestyle management or lifecare. Why wait until you are ill to learn what will make you sick? Why wait until you are fat to learn how much exercise you need? Working with your doctors, human and hand held, will help answer these questions before they become problems.

Which is really the promise of merging semiconductors with genetics. Cutely named devices are great, but widespread improvements in healthcare are better. The possibility that anyone with the interest could affordably test themselves for genetic traits is amazing. That may alter the way we think of genetic information, our health, or even our identities. These are game-changing trends, and it’s exciting to see them make their way to market. Hopefully DNA Electronics, and Prof. Toumazou will develop the biological sampling side of the SNP Dr. as quickly as planned so that we can start seeing the benefits of those trends in a few years.

After that, its back to breeding different technologies to produce crazy offspring devices. Particle colliders and Twitter…Tweetbomb?

[photos courtesy of DNA Electronics]

[video credit: Number10TV]