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Iowa s BioForce Nanosciences Building Array Biz on its Prowess in Atomic Force Microscopy

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Eric Henderson, the chief science officer of BioForce Nanosciences of Ames, Iowa, won’t argue with the characterization of his firm as essentially an atomic-force microscopy company, but this year, BioForce is diverging from that path, marketing a commercial array technology capable of performing at the nanometer scale.

The company, which has 16 employees in a 4,000 square-foot office (with a view of a cornfield) in the Iowa State University Research Park, and is in its 10th year of existence, currently sells AFM products such as an AFM probe cleaning device, and tungsten microspheres.

Founded by Henderson along with his brother, Will, and a former student, Curtis Mosher, in 1994 and incorporated in 1997, BioForce hopes this year to market products that build on the foundation created by the patents, and AFM applications — the NanoPro system, which consists of the NanoArrayer device that places molecules at defined locations on a surface with nanometer spatial resolution; and the NanoReader, a customized AFM optimized to read NanoArray assays based on the technology.

The company illustrates that in the maturing microarray market, dominated by relatively established companies, there are innovative technologies developing with potential to grab market share.

The first NanoArray application, the ViriChip, was the subject of a paper published in the Jan. 19, 2004 edition of the Institute of Physics journal, Nanotechnology. The ViriChip is a 4-mm x 4-mm silicon chip with antibodies printed on the surface. The viruses that attach to the antibodies are detected using an atomic force microscope. Saju Nettikadan of BioForce, and co-authors from Iowa State University and Des Moines University, describe the ViriChip and its use in detecting six different strains of coxsackievirus B, which some suspect as a key factor in deaths after organ transplants in humans.

“The paper is proof of concept [for the ViriChip],” said Henderson. “But, it is not the HIV chip, the hepatitis chip, and the papilloma chip, which are the ones currently on the drawing board because we want to hit the very big virus markets.”

The ViriChip, Henderson said, will be tested and validated this year, with the hopes of wide marketing in 2005, after validation.

The company is concentrating on protein-based testing, using its platform, said Henderson, because it is an operational space that is “largely unprotected” [by patents].

“As a small company, we have to be very conscious of what we can and can’t do without infringing, or even appearing to infringe, on other people’s space,” he said.

As the company arrives at this stage of commercialization, targeting break-even by the end of 2005, it is seeking at least $7 million in a next round of financing.

Thus far, BioForce has raised $3.5 million in private-equity investment, including a $2 million investment from Société Genérale Asset Management of Paris that closed in November 2002.

The company has also been successful in obtaining SBIR government research funding, winning 14 grants for a total of more than $4 million dollars. Henderson said the key to winning grant writing, at a 38 percent success rate, has been to always include in the proposals innovative components that are also commercializable.

“I think we have commercialized everything that we have created from SBIRs, and that gives us some credibility,” he said. “The irony is that once you get to the size we are now, where you have to do something to make a quantum leap financially, you no longer become eligible for SBIR grants. It’s a weird paradox: They will let you get so far, and then they hamstring you.”

Given that most venture capital firms usually like to invest in companies that they can easily visit, BioForce’s location, far from the VC centers of the US in California, New York and Boston, can pose a hurdle. But Henderson remains optimistic.

“We have interested parties for the next round,” said Henderson. “No one has committed, but things are looking very promising.”

Is Smaller Better?

The 47-year-old Henderson is a man clearly smitten by the power of the AFM, which uses a spring-mounted probe to image atoms on the surface of a material.

“It’s like a Caterpillar [tractor],” he said. “It’s a robot. You are here in the macro world and you twist a knob and the little finger down there does what you want it to do. It is a window on the nano scale and that is incredible. It is a direct mechanical contact with the tool and what you are trying to work on.”

Henderson can tell you that he was the 18th customer to purchase an AFM from Digital Instruments, which was acquired in 1998 by Veeco Instruments located in Woodbury, NY.

Today, Virgil Elings, the founder of Digital Instruments and AFM probe manufacturer NanoDevices, sits on the scientific advisory board of BioForce, which sells AFM products such as an AFM probe cleaning device, and tungsten microspheres. The company, however, doesn’t sell the instrument.

“That market,” said Henderson, “is 80 percent owned by Veeco. They own virtually all of the intellectual property related to that technology. By rational design, we don’t sell it. But, if all goes according to plan, some of the methods-of-use patents related to AFM would be BioForce’s intellectual property estate.”

BioForce received its first US patent in June (see BAN 6/11/2003), and has three more core patents pending among 11 US applications.

But, on whether the ability to test a single molecule can produce the next evolution of microarray analysis, Henderson is hesitant.

“We can do a single molecule experiment,” he said. “But, what does that tell you? It’s either on or off, but it doesn’t tell you about statistical meaning. It could be a random event, but you can’t tell. If your life depends on the test, it has to be correct. Spelling your name with antibodies would be an incredible Science cover article, but you can’t make that into something a doctor would use.”

Today, BioForce can place a million spots on a 4-mm square chip. “The only reason [it] is that big is that we handle [the chips] with forceps,” he said.

“I believe you can build a test on the nanoscale with 10 spots on it, and use one microliter of blood to tell how someone is progressing through cancer treatment,” he said. “You don’t need to look at 30,000 genes to do that. We wouldn’t build a chip for every virus on earth, but we would build one that would detect all the different viruses on a horse, for example.”

This year, the company is looking to miniaturize one component of its system, the reader for products like the ViriChip.

“The trouble with an AFM is that it costs way too much for this application,” said Henderson. “It costs $120,000, when it should be $30,000 for reading ViriChips.”

The BioReader, he said, will be a toaster-sized instrument that reads the chip and produces data. The company has a beta version available and plans to have a full commercial version ready by the middle of the year.

Pathway to the Clinic

BioForce plans to partner with diagnostics labs or state agencies that would test and compare the technology. The validated results of the collaborations, he said, could be used in making regulatory applications.

The company has a collaborative arrangement with Fort Dodge Animal Health, a division of Wyeth.

It is a long way from this point to a time where its instruments are common in pharma, Henderson admits.

“It is difficult to speculate about the probability of success because until people develop useful assays with this technology, pharma is going to be the last to look at it,” he said.

BioForce, he said, will just continue to drive forward.

“We have no shortage of potential and we have been trying hard to stay very focused,” he said. “The demise of small companies is that they can do so many things that they end up doing nothing. We are trying to stay focused, commercializing the NanoArrayer because it is our own tool, patent pending, and come up with our own products. And, then, take it from there, with our revenues coming in.”

— MOK

 

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