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MIT s Francesco Stellacci on a Cost-Effective, Natural Way for Printing Arrays

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Francesco Stellacci
Assistant professor of materials science and engineering
Massachusetts Institute of Technology

At A Glance:

Name: Francesco Stellacci

Title: Assistant professor of materials science and engineering, Massachusetts Institute of Technology

Educational Background: 1998 PhD in materials engineering, Politecnico di Milano, Italy


Francesco Stellacci, an assistant professor at MIT's department of materials science and engineering, focuses on nanotechnology and has a special interest in metal nanoparticles. Recently, his lab also made a foray into nanoprinting, inventing a stamping technique that could have promising applications for manufacturing DNA microarrays in a faster and more cost-effective manner. This month, his research group, in collaboration with scientists at both MIT and Virginia Commonwealth University, published a paper describing the technique, entitled "Supramolecular Nanostamping: Using DNA as Movable Type," in Nano Letters (Jun 8;5(6):1061-1064).

Can you explain how supramolecular nanostamping works, and where the idea for it came from?

It is actually inspired by nature, it's a bio-inspired printing technique. When nature wants to reproduce all of the genomic information of DNA, it uses supramolecular forces to do that. What I mean by that is, you have a DNA double helix, and an enzyme tells the double helix to de-hybridize, so you form two single strands, and then the RNA polymerase approaches one of the two strands and copies the information, base by base. At the end of the day, you have a double helix, formed by DNA and RNA. This one is again approached by an enzyme, de-hybridizes, the messenger RNA leaves the nucleus of the cell and goes outside and brings information.

[In a way] this is a printing technique, because you started with a certain sequence of bases, and you ended with comparable sequences of bases, and this is a large amount of information that has been transferred from a molecule to another. It's great because it has been transferred with sub-nanometer resolution, and it's at room temperature and uses no chemicals, like etching chemicals or things like that. We took inspiration from this, and [saw] that the beauty of DNA is that it can hybridize and de-hybridize as many times as we want.

What we have developed is a method where on a surface you have a pattern made of DNA molecules of known sequence. We take that surface, that's our master, and we put it in a solution that contains complementary DNA, [which] recognizes its complement and [binds to it]. We use complementary DNA that has been synthesized with a sticky end pointing up. By sticky end, I mean [a chemical group] that will form a bond with a surface; for example, we can use thiol if we want to print on gold. Once this hybridization has succeeded, we take our substrate out of the solution, we take [another] substrate, and we just put it on top of the first one. At this point, the sticky end binds to the second substrate. And then we need to do it exactly how nature does; we need to tell the DNA that we want it to de-hybridize. So we just heat it up to [a certain temperature], depending on the chain length, and the two substrates just pull apart, and now the second one has a mirror image of the first one's pattern of DNA. This is our printing technique.

So, what is the beauty of it? Just like in nature, we [use no] etching chemical, no high temperature, only water and a salt. The other thing is that exactly like in nature, our information content is very high. Say that on a surface we have two dots composed of two different sequences of DNA. We can print them both at the same time because we can put them in a solution containing the complement and they will find the right position.

What are the advantages for using this to produce microarrays?

Say you have a bioarray that is composed of 1,000 different dots of different chemical composition. Our method is the only one out there that can print it just in one step. We need a solution [containing] complementary [DNA strands], then take [our substrate] out and just stamp it on a surface. Once you have a master stamp, the DNA microarray, then, in order to produce a copy of a master, we need just one printing cycle. Right now, the number of steps that you use to print [a microarray] is the main reason for high cost. Affymetrix uses on the order of 350 steps to produce one DNA microarray. [With] the material used, one could claim that ours is even a little bit less expensive, but I am not sure. What ends up on the microarray is the same, but instead of 350 steps, you use one.

How much have you scaled your technique up already?

We have printed very small things, like four dots. Personally, I believe that going from four to 1,000 [requires] a lot of engineering. I am not sure that this is really something to do in academia.

Has anybody expressed an interest in developing this for commercial purposes?

There is some definite interest, yes. I can't disclose at the moment [by whom]. I haven't talked with microarray companies so far.

Have you applied for a patent to protect your method?

Yes, I have two patent applications pending.

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