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NanoInk VP Guy della Cioppa on Why We Need Protein Nanoarrays

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At A Glance

  • Joined Chicago-based nanoarray startup NanoInk as executive vice president for business development in September 2002.
  • Spent 13 years at Large Scale Biology, most recently as vice president of business development, before that as vice president of genomics.
  • Before that, spent 5 years in various positions in corporate R&D at Monsanto.
  • PhD, Biology, from UCLA.
  • NIH Postdoctoral fellow at the Worcester Foundation for Experimental Biology in Worcester, Mass.

What made you leave Large Scale Biology after a 13 years to join NanoInk?

I see some very interesting opportunities at the interface between nanomaterials and biolog ical systems. It's actually a specialty area of nanotechnology that's called “nano-bio.” I have been following the nanotech space for quite some time, and it's clearly a growth area, it looks to be the next major investment wave.

But the real reason I left, [was that] I knew the acting CEO of NanoInk, and he was pitching the opportunity to me from the business standpoint. I started doing some diligence on NanoInk and was just phenomenally blown away with the quality of the science, the brand-name science coming out of Chad Mirkin's lab at Northwestern — the number of publications he has [published] in the journal Science alone., and then the quality of the people that they were able to hire at NanoInk.

The other thing that really got me excited was the fact that at the time I joined, there were only about 12 employees, and the company was already shipping products and booking revenue.

Why were you attracted by a small company?

I am a risk taker, I like new entrepreneurial startups, and I spent 13 years at Large Scale Biology and went all the way through the IPO process.

I am always looking for the next technology wave, and the people who are catching the next technology wave at the same time you are catching the next investment wave.

That's a nice place to be.

Why do we need nanoarrays?

When you start to miniaturize down to the nanoscale, there are certain reactions that you can follow on a nanoarray that can give you certain pieces of information that you don't get by studying much larger-scale microarray types of interactions. There, you are mixing very large solutions of proteins together, and you have just a giant sea of binding events, as opposed to looking at very specific binding events on a natural molecular structure, that you can then directly measure at the atomic level with an atomic force microscope. It is really a different scale and a different level of understanding of protein-protein interactions.

One obvious advantage of nanoscale is the increase in density. You can imagine being able to put down very large libraries, for example of peptides and proteins, and have each one of those spatially resolved on a silicon chip, which you could then probe with whatever analyte you want to probe. You can imagine putting down 106 to 1012 different molecules, and that requires ultra-miniaturization down to the nanosale.

Speed, throughput, cost — miniaturization provides all of those advantages.

What is the advantage of using an atomic force microscope to create the chips?

You can assemble macromolecular structures from the bottom up using dip-pen nanolithography. The atomic force microscope is a very interesting instrument, and I am absolutely not an authority, but having said that, the atomic force microscope can do a very detailed, very high-resolution topographic map of protein-protein interactions. You get a topographic map of how another protein or how a protein-ligand interaction is actually physically oriented onto a macromolecular structure. Also, there are types of atomic force microscopes that can measure frictional coefficients — for example, the surface of a protein complex. So you can get other information besides just topographical information. I think that piece of instrumentation is going to be widely used very quickly here in the life sciences, especially in the whole array space.

How easy will it be to multiplex the measurements? How easy is the jump from one to 32 to 10,000 pens?

It's actually a very easy jump to make from the manufacturing standpoint, because this really is standard MEMS technology to manufacture these pens. There is really no new technology that has to be invented to manufacture pen systems, and probably the best example of the type of technology that's out there right now being commercialized is IBM's millipede. The millipede is 1,024 AFM pens on a microchip. Each pen of this 1,024-cantilever array has a very fine tip that is only a few nanometers, and it can make very fine indentations into a thin film, and create a nano punch card. The technology is there, right now, to manufacture these complex pen systems. What's new is NanoInk's invention, which came by way of Chad Mirkin at Northwestern, to actually use an atomic force microscope to write structures, to ink those tips and to put chemistries down in a very specific fashion on a nanoscale. It's a nanoprinting device.

NanoInk already has a software product — for what?

The software allows you to convert a conventional AFM from a device that simply reads to a device that writes. Here is the simplest way to imagine it: Let's say you have some text that's written on a piece of paper. What you want to do is feed that into the atomic force microscope and have that converted to a bit-map image, and then all of that information directs the movement of the atomic force microscope tip to draw the structure that's been written on a piece of paper. It's essentially a software to control how the inked tip moves, where it moves, and how long it stays in contact with the surface.

Now you have a new product coming out, the DPN writer. What does it do?

That is a dedicated atomic force microscope that is built from the ground up to do dip-pen nanolithography, and that would be controlled by a software. We will have our own atomic force microscope tips that will function kind of as the disposable razor blade of the razor / razor blade business model. The plan is to bring this out in December.

How many pens will that system have?

It will have one or more. It's unlikely that the first-generation product will have 10,000 pens. It will be a single- to a multiple-pen system.

What is your initial business model?

To sell the instruments, the pen systems, and then the inking systems that will either provide ink to the pens or pre-inked pens. You can think of the atomic force microscope as kind of the picks and shovels of the field. During the gold rush, the people who made all the money were the people selling the picks and the shovels, and that's typical for any industry, and nanotechnology is a brand new industry. The first people in, the first people to make money and make a big foothold are the providers of the new platform tool. And that's what we believe dip-pen nanolithography is: It's a platform tool that has wide applications, not only in life sciences but very broadly. And we anticipate that this will be the basic platform on which the nanotechnology industry operates to deposit soft molecules by this soft lithography process.

In the life sciences, will you become the new Affymetrix?

Affymetrix is a kind of a single application [com pany]. We actually believe that the dip-pen nanolithography platform is so broad that there will be room for multiple foundational applications, such as an Affymetrix- type chip, a high-density protein chip, a virus chip, or other macromolecular array-type chips. You can imagine you can write any type of a structure onto a silicon surface or a variety of different surfaces. You can write spliceosomes, for example — macromolecular structures. Some of the combinatorial chemistry opportunities are also very interesting. A lot of this work is in progress right now, and there are several publications in press that will be out over the next couple of months on doing direct-write of certain proteins and complexes.

What kinds of partnerships are you seeking?

[Partnerships with] microelectronics companies, life sciences companies, aerospace companies, to develop applications of DPNs specific to that industry. To use DPN as a discovery tool to do nanoscale fabrication of materials, and then ultimately, to use DPN as a manu facturing tool to manufacture new products based on the dip-pen nanolithography.

But you already have some research partners, right?

We do, we have quite a few scientific collaborations. The Institute at Northwestern is one of the top, if not the top, nanotechnology centers in the world. It just opened a brand new nanotech center on Oct. 14.

[NanoInk is] located in Chicago simply because Chicago has now become the hub, it is one of the major centers for nanotechnology. There are three nanotech startups there right now — NanoInk is just one — and a couple of others that are about to spin out of some of the major centers there. You have got Argonne National Lab, Northwestern, University of Chicago, University of Illinois [at Urbana-Champaign] — these are all incubators for new nanotechnology development.

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