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Winter 2009

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29 www.hplusmagazine.com Dr. chad Mirkin has a singularly impressive résumé — he is the director of the International Institute for nanotechnology, and serves as a professor of chemistry, medicine, biomedical engineering, materials science engineering, and chemical and biological engineering at northwestern University. In 2008, he was recognized as the third- most cited chemist and the most cited nanomedicine researcher in the world. In april of this year he was named as a member of Barack obama's Science and Technology advisory council. Mirkin is perhaps best known for the development of a technique known as dip pen nanolithography, a method of nanopatterning that uses an atomic force microscope much like a quill pen to deposit a molecular "ink" onto a substrate. His contributions to medical diagnostics and therapeutics are a bit more obscure. The diagnostic assays developed in his lab use chemically-functionalized gold nanoparticles as a probe to detect targeted DNA sequences, as well as the presence of proteins that can indicate disease. The applications of this technique range over a broad spectrum, including everything from detecting the flu virus, to accurately diagnosing Alzheimer's, to finding the protein markers that can indicate cancer. Recently, his bio-barcode assay was integrated into a device that uses blood serum passing through microfluidic channels to allow the assay to take place without assistance. This kind of system may soon lead to handheld devices capable of diagnosing a wide range of disease in minutes, using only a small sample of blood. Dr. Mirkin spoke with h+ via telephone to discuss some of implications of this technology. h+: can you talk about the diagnostic assays that you have developed? CHAD MIRKIN: In the diagnostics area, we're using nanoparticles made of gold that have DNA strands attached to them. They can be used to latch onto disease targets with specific DNA codes that then provide some sort of colorimetric signal that tell us that that particular target is present, and how much is present. And those are commercial systems now. There is a whole diagnostic system called the verigene system which is sold by Nanosphere, a public company that we started about 10 years ago. There are now four FDA clearances and hopefully many more on the way. h+: can you tell me a little bit about how the bio-barcode assay works with lab-on-a-chip technology? CM: Well, that is not a commercial assay yet... it's a research assay. But it is an assay that is extraordinarily sensitive—it allows you to detect protein markers at orders of magnitude lower concentration than you can with conventional commercial diagnostic tools. And as a result it's opening up all sorts of applications in oncology research and medical diagnostics, but also in the testing of things like Alzheimer's disease and HIv. Anything where a high sensitivity and low marker concentration is critical, this type of technology can have a major impact. The microfluidic part of that is developing a system that is highly miniaturized, and can take a sample and basically treat that sample with chemical reagents on a little microchip that presents it in the form that you can detect the different disease markers of interest. So DNA does not come packaged as something that is freely floating in blood. It's inside cells, and cells have to be lysed. The DNA has to be broken apart. It's a duplex structure. And then you have to have a system that can capture the target and tell you how much is present. And so the microfluidic bio-barcode assay actually does that from beginning to end and creates a device that truly can be a portable, point-of-care device. It certainly could be used in hospitals, but likely also in the doctor's office and maybe even the home. That's the goal of all this. Bill Gates wanted a computer on every desktop and he actually got two in many cases. We'd like a medical diagnostic system in every home in the world. h+: What kinds of tests do you imagine these devices will be capable of performing? I know you've been working with prostate cancer protein markers…. CM: Well, everything! Every disease where there is a marker present we can have an impact because our assays are more selective. And they're more sensitive than what's out there. They're also lower cost and they have been designed so that they can be run off of relatively simple instrumentation. And that means you no longer have to rely on these remote labs with this big bulky instrumentation that has to be in a stationary state and where samples have to be sent. This really opens up the whole field of point of care diagnostics. h+: how far out do you think we are from seeing these sorts of point-of-care diagnostic systems readily available for standard practice in the First World? CM: They're here. The verigene system is launched. It's in hospitals around the country. It will scale rapidly. Really, what we are waiting for is just an increasing menu [of tests]. Because the beauty is that with one instrument you can have almost an infinite number of assays, just different cartridges. h+: It sounds like science fiction. CM: To me, it's amazing that it hasn't happened before. People 100 years from now will say, "These guys were in the Stone Age. I can't believe they had to send a sample of blood, saliva or urine to an outside lab and then wait days to weeks to get the test results." The type of technology should—and now does— exist to do it at the point of care, to do it in this case in a couple of hours. But I think one day it will be a few minutes. Ian Monroe is a journalist and technology geek currently living in Chicago. He's on the web at ianmonroe.com nano probeis IAN MONROE An IntervIew wIth Dr. ChAD MIrkIn PeoPle 100 years from now will say, "These guys were in The sTone age." Nanosphere http://www.nanosphere.us resources These guys were These guys were "

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