BOSTON — In an attempt to reposition its technology as a drug-discovery tool, Troy, NY-based Applied Biophysics has for the first time shown off a 96-well version of its electrical impedance-based cell sensing technology at IBC's Drug Discovery Technology conference, held here last week.
Applied Biophysics — which invented the concept of measuring cell activity using electrical impedance — has sold at least 80 units of a lower-throughput 8-well system since it was founded in 1991, Charles Keese, the company's co-founder and vice president, told CBA News last week.
Most of these units have been sold to academic scientists interested in using them for basic research applications such as cell migration, cell morphology, and cell culture wound-healing assays, and Applied Biophysics had enjoyed a relatively competition-free market.
However, as the demand for new cell-based assay technologies in drug discovery has grown in the past decade, particularly in the last few years, Applied Biophysics now finds itself with competition from MDS Sciex and Acea Biosystems, both of which are marketing cell-based assay platforms based on the same concept of electrical impedance measurements. Acea has been doing so for a little over a year (see CBA News, 1/18/2005); MDS Sciex, meanwhile, unveiled its platform for the first time here last week (see related story, this issue).
Despite the fact that the technologies are all based on electrical impedance measurements, there are subtle differences between them that will determine into which drug discovery niche they will fall, Keese said. One of the main differences, he said, is the size of the electrodes used to measure impedance changes.
"The original invention was in 1984, and the decision was made then to publish, not to patent. … We've been trying to improve our IP situation. This is after going a lot of years without doing what we should have done earlier."
"Our technology makes use of small electrodes that are spaced sufficiently far from the counter electrode or from each other that we know the current path is through the cell layer," he said.
Acea's technology, on the other hand, has an "inter-digitated" electrode arrangement, according to Keese, that allows "sneak paths" under the cell, and "prevents you from doing any realistic modeling," he said.
"Once you have a small electrode, you know the current path, and you know it has to go beneath the cell and between the cell junctions," he added. "The other thing you get is the ability to see cell movements in real time. Because you're looking at a very small population of cells, the movements of which are random, generally it wouldn't show up if you looked at a large population, because one area would cause the impedance to go up, and another would cause it to go down."
As employees of GE's Research and Development Center in Niskayuna, NY, in the mid-1980s, Keese and colleague Ivar Giaever first developed a method to use electrical sensing to monitor the motions of cells, and published a pair of papers on it. Giaever joined Rensselaer Polytechnic Institute as a professor in the late 1980s, and Keese joined his lab soon after. From there, the two further developed the technique to include a way to model the information from impedance measurements into meaningful data.
Keese said that he and Giaever "didn't immediately see the commercial importance" of the technology, but realized that they could continue to develop it with Small Business Innovation Research support from the National Institutes of Health. They finally founded Applied Biophysics in 1991 after completing the required phases of SBIR funding.
"But at that time, it was still just the two principals — Ivar and I — that were trying to run this," Keese said. "The word was getting out very slowly, mostly through publications." In the late 1990s, he added, the scientists hired current vice president of marketing Christian Dehnert, "and that's been a dramatic change in our whole way of doing business," Keese said.
For having invented the technique — which Applied Biophysics calls electric cell-substrate impedance sensing — the company does not have as firm a hold on the intellectual property surrounding it as one might think.
"The original invention was in 1984, and the decision was made then to publish, not to patent," Keese said. "With Chris coming on board, we've been trying to improve our IP situation. This is after going a lot of years without doing what we should have done earlier."
This, in turn, "has allowed MDS Sciex to have a lot of room to come in" with its technology, which Keese said is more similar to Applied Biophysics' technology than Acea's is.
Currently, Applied Biophysics has the exclusive rights to one US patent, No. 5,187,096, which covers the basic cell monitoring apparatus. Now, Keese said, the company has filed additional patents covering specific applications such as monitoring migration of endothelial cells and wound healing.
Acea, meanwhile, has three patents pending for its technology, with an eye toward more specific drug-discovery applications. Applied Biophysics' patents and Acea's patents were filed around the same time, and industry players will be eager to see how the intellectual property rights play out. It was unclear as of press time whether MDS Sciex has filed for patents on its technology, which, while more closely related to Applied Biophysics', purports to provide more specific drug-discovery capabilities such as detecting GPCR and tyrosine kinase receptor activity.
Applied Biophysics' Dehnert said that its detection instrument sells for about $45,000 — slightly less than the $65,000 Acea's instrument costs, and a great deal less than MDS Sciex's instruments, which company officials said will likely sell for $350,000 to $400,000.
Regardless, Dehnert said the competition is a good thing.
"I think it's a real benefit to us, because it basically spreads the technology," he said. "Fundamentally, this whole idea of impedance is pretty foreign to biologists. So as the other companies help educate our market, collectively, then we all gain. And as the technology becomes more accepted in the market, we all gain from that, too."
Though its customers are mostly academic users, Applied Biophysics now plans to divert its attention toward the drug-discovery market and tweak its platform as needed. For instance, Keese said, the company has preliminary data showing how it might be used to electroporate cells using higher voltage to introduce compounds or other biological entities, and then tune down the voltage again to monitor the cells' reactions.
Now that it has competition, the company is keeping tight-lipped about other application areas.
"There are other areas, though," Dehnert said. "We're certainly thinking of different arrangements of arrays, and different problems we can attack."
— Ben Butkus ([email protected])