In 1955 while addressing the National Academy of Sciences Richard Feynman stated "Scientific knowledge is a body of statements of varying degrees of certainty." As usual, Feynman's statement was spot on, and holds true decades later. In his famous "Plenty of Room at the Bottom" lecture Feynman talked about what we now call nanotechnology, and all the different applications. Here I am, half a century later, working "at the bottom" and living in a world of uncertainty. I hope to share some of the exciting discoveries at the nanoscale and explain how they apply to my passion of biotechnology- as well as the everyday world. Learn more about Nicholas Fahrenkopf
My posts are presented as opinion and commentary and do not represent the views of LabSpaces Productions, LLC, my employer, or my educational institution.
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One of the research scientists at my college forwarded me a Nature article he thought I’d be interested in. This was the same guy who wanted to know how you feed DNA, so I was wary, but I took a look anyways. Now here I am breaking one of my only blogging rules and am writing about my own research. The paper came out in July in Nature titled “An integrated semiconductor device enabling non-optical genome sequencing” – it is open access too so take a look (after you finish reading here of course!)
My research is on the interactions between DNA and hafnium oxide. Pretty bland until you put together the puzzle piece that hafnium oxide is used by Intel and others in their cutting edge processors. We think we can be better (Faster! Stronger!) DNA sensors with field effect transistors that incorporate hafnium oxide, but first we have to stick the DNA to our sensor, and understand those interactions. Sensing DNA is nothing new. You could argue that Rosalind Franklin and crew were “sensing” the A or B forms of DNA using x-ray imaging. Most commonly nowadays are fluorescent stains like DAPI which are used in biology to image where the DNA is in a cell. There are a host of microbiological techniques to isolate and test for DNA: gels, PCR, HPLC, etc. Test for a specific sequence of DNA for a specific purpose is an engineering and real world problem.
Say you have a white powder that came to an office in the mail. Is it anthrax? Or flour? Is the meat in a factory safe to eat or laced with bacteria? Does a student have novel-H1N1 flu, or just a cold? The traditional methods for answering these questions often require cultures which can take days, or PCR which is expensive and requires a lab. So for quite some time now engineers have been looking for fast, simple tests to these questions. Many doctor’s offices now have “Rapid Tests” which are quick and easy, but not conclusive- the false positive/negatives are significant that the traditional tests are usually also ordered. I won’t go into all the possibilities, but researchers have nearly exhausted every possible kind of detection scheme in R&D settings. And yet, none have been widely deployed for one reason or another.
This is why this Nature article is really interesting. In it, the authors outline their DNA sequencing (not just sensing!) device. Using nanofabrication, devices are created that trap the DNA of interest in a well, and then exposed to DNA polymerase. As bases are added the electronics can detect which base was added. This is done over one million times- at once. That’s the real advantage of semiconductor based devices. There are 1.2 million wells, testing the same sample, at the same time. The data is then synthesized to sequence the sample. Yes, there are other ways to sequece DNA, in the lab, using a commercial solution. But again, its all about better, faster, stronger…
Since the late 1990’s researchers have been sensing DNA using field effect transistors. But this paper not only sequenced the sample (instead of detecting a specific sequence) but did it in a highly parallel manner. And here’s the kicker: it’s a commercial solution, not a laboratory prototype. It isn’t a cobbled together series of laboratory equipments that have been strung together so a graduate student (after 6 years of work) could sequence a sample of DNA (on a good day!) It is a tool anyone can buy, and have their samples sequenced. And if the idea of creating this commercial tool for researchers doesn’t tickle your fancy, the authors used a sample DNA to sequence in their paper labeled G. Moore. That’s right: G. Moore.
As a psuedo-biologist that didn’t click at first, but Gordon Moore, of Moore’s Law fame, donated his DNA to be sequenced. Moore co-founded a little company called Intel. Before starting that company he published an observation that the number of transistors in an integrated circuit was doubling every year. He predicted that this would continue and in ten years- 1975- there will be a whoping 65,000 transistors on a chip. That doubling has held steady for more than 50 years and drives the multi billion dollar nanoelectronics industry. Today, there are on the order of 1,000,000,000 transistors on a chip! The authors got this nanoelectronics icon to donate his DNA for their solid state sequencer. That’s just freakin’ cool in my book.
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