Dr Henk Postma, CSU Northridge
Ben - As an understanding of our genes and that of our food and everything else becomes more important in knowing what diseases we may develop and, in fact, how to treat them and avoid them Ė fast an efficient ways to sequence our genome becomes ever more important. Dr Henk Postma for the California State University at Northridge thinks that nanotechnology could have the answer. Hello Henke, thanks for joining us. How would we use nanotechnology to read DNA?
Henk - The idea has been kicked around by some scientists for a few years and the idea is that if you would have somehow separate electrodes connected to a single base of DNA molecules then if you would read its conductance then you could tell the difference between the types of A-C-G-T in a chain. If you could somehow scan your electrodes on the molecule you could read off the sequence. What we are planning to do is we are planning to use electrodes that are fixed and then are immersed in a reservoir of liquid. We would introduce DNA on one side then we would apply an electric field and the electric field would drive the DNA molecules through that pair of electrodes. While it goes through you read off the conductance.
Itís deceptively simple but it turns out itís actually quite hard to do and people have been trying to do this with big electrodes. If you make electrodes out of gold materials they typically are very thick, letís say about 20nm thick. Then your DNA molecule has a distance between the different bases of 0.3nm. You would have at any point in time 60 bases in between your electrodes so itís very hard to resolve any kind of electrical signal due to a single base.
Ben - So youíd get an indication of what bases might be between your electrodes but you wouldnít be able to read each one?
Henk - Exactly. Youíd get some kind of statistical measure of the average, perhaps. What Iíve been proposing is to use graphene as the electrode. Graphene is a new material that was discovered by Andre Geim in Manchester, in your country, about 5 years ago and itís a single layer of carbon. It is extremely robust, it is a very good electrical conductor and because itís a single atom thick if you make electrodes out of those you would be able to resolve the single bases inside the DNA molecule. That's the basic idea of what I'm working on.
Ben - It sounds like a deceptively simple idea but you also imply that it's just an idea at the moment. What do you think the challenges will actually be when you can make this happen?
Henk - A few of the things have been solved already by several people in the world. One of the things you need to do is you need to be able to make a membrane that can be immersed in a liquid and survive the typical capillary action that is associated with having something as thin as that in the liquid. People have solved that. They've made thin membranes. One of the things you need to do is you need to make a tiny gap and we've identified a few potential technologies that allow us to make a thin gap. That's the first thing that we're actually working on right now. That's the first thing that we need to be able to do.
Ben - This will need to be a gap that's exactly the right size to let DNA through, one base at a time.
Henk - Exactly. It has to line up very nicely because if you would even make you gap about one nanometre thicker, wider than it is in the ideal case your current drops by several orders of magnitude. It would be very hard to detect any kind of signal. That would be the first challenge, I would say.
Ben - What are the advantages of doing this? How quickly could you actually sequence the human genome? We know there are 24,000-ish genes that actually work and a load of stuff that may or may not be junk. How long do you think it would take?
Henk - Well, actually the junk DNA is actually a very interesting issue. We're proposing to sequence the whole thing regardless of whether we consider something junk or not. That is an open question, whether junk DNA ha s some kind of a function. Extrapolating from our read-time for a single base I estimate it will be about 3 micro seconds so, if you would be able to use such a device for one single DNA molecule of the human, it would take about 2 hours to read the whole thing.
Ben - That's really incredible. Just one last question, how much is it likely to cost to sequence one human genome?
Henke - Well you would have to get some electrical equipment, make some material. Graphene actually is surprisingly cheap. I'm not sure, my lab is very expensive but I presume that if you want to do it again you don't want to make any extra investments. I won't be able to put a number on it! That's something that has to be figured out later but because it's a single device and there's no extra preparation that is needed for the DNA material you can just put it in the liquid and you'll be done with it. You don't need to do any PCR amplification or radio labelling or fluorescent read-out or any gel electrophoresis. All those techniques are not required. It's a very basic experiment, actually.