With its expertise in biochips for cell biology applications, Aviva Biosciences certainly has fertile ground to grow in. But rather than building analytical systems around its chips all by itself, the 16-person San Diego-based startup decided to develop a few chip types for specific applications, then license the technology to an instrument or diagnostics partner that will bring them to market. “We are almost a biochip intellectual property licensing house,” said Eric Lachenmeier, Aviva’s director of business development.
The company, however, started with a patent it licensed from somewhere else — Tsinghua University in China — but has since developed its own technologies, some in collaboration with scientists from Tsinghua. Jing Cheng, one of Aviva’s three founders and now a director, was a principal scientist at Nanogen in the late nineties and is now a professor at Tsinghua University and research director of the Beijing National Biochip Research and Engineering Center in China. The other two founders are Julian Yuan, Aviva’s first CEO and current vice-chairman, who spearheaded the $5 million Series A round of financing in early 2000, and Lei Wu, the company’s COO and vice president of system development, who like Cheng came to Aviva from Nanogen. Cheng also brought on board CEO Peter Wilding, a professor of pathology and laboratory medicine at the University of Pennsylvania, where Cheng was a postdoc in the mid-nineties.
When Wilding joined the company in September 2001, he focused Aviva on two applications it had been developing for almost a year: ion channel electrophysiology and isolation of rare fetal cells from blood. “We looked at a fair number of opportunities, and we selected those two based on an optimum mix of time-to-market, proprietary technologies, and market opportunities,” said Lachenmeier.
This strategy is beginning to pay off: Last week, Aviva announced its first partnership, with Axon Instruments, a company specializing in software and instruments for electrophysiology and microarray analysis. The two partners want to co-develop a high-throughput automated patch-clamp system for measuring the conductivity of ion channels in cell membranes, and are planning to release a product by the end of this year. “Axon is recognized as a trusted and reliable provider of systems into this marketplace, so we gain immediate credibility by partnering with them,” said Lachenmeier. The deal will also hopefully provide Aviva with some income — the two companies have a revenue-sharing relationship for every chip sold.
Aviva’s contribution to the system is a disposable patch-clamp chip, to which Axon holds exclusive marketing rights. The patch-clamp technique is of great value to drug companies for determining the effect of drugs on ion channels, but it still relies on a laborious process of locating a cell under a microscope, positioning a glass pipette over the cell, making contact, and establishing a good seal. The main goal of the new chip is to streamline this process. “There is a big gulf between what the technology today can deliver and what the industry would like to be able to accomplish,” said Lachenmeier. “It’s a rate-limiting step.”
The patch-clamp chip contains channels and electrodes that can put forces on individual cells and draw them to an aperture one to two micrometers in diameter. Once the cell is positioned over the hole, a high-resistance seal is established and measurements of ions flowing through the channels in the cell membrane can be taken. According to Lachenmeier, a skilled electrophysiologist can perform about ten patch-clamp experiments per day. The new instrument, which will contain a cartridge with multiple chips,will increase this number to over 200 readings per day, he said, and up to 1,000 in the future. One challenge is establishing a durable seal each time, and Aviva has reached up to a 90 percent success level with this task, he added.
Pharmaceutical companies, Lachenmeier said, “represent the sweet spot of the market” for the patch-clamp chip. In competing for pharma business, however, Aviva may not go unchallenged. Several other companies, including Molecular Devices, CeNeS, and Nanion Technologies, are working on competing systems that are poised to come out within the next year or so.
But Aviva is not putting all its cells in one chip. It has also been working on a filter-like cell separation chip for prenatal diagnostics. Up to now, amniocentesis has been the standard method for testing fetuses for conditions like Down Syndrome, but it carries a considerable risk of miscarriage. A less dangerous alternative is to isolate rare nucleated fetal blood cells from the mother’s blood, but it is difficult to consistently recover enough of these cells for analysis. To improve the method, Aviva has developed a filter chip — along with a number of up-front chemical steps — that allows the disk-shaped red blood cells of the mother to pass but traps the spherical fetal red blood cells. The new method has a recovery rate of over 60 percent, significantly higher than current ones, Lachenmeier said. While nobody is currently offering a diagnostic test kit based on fetal blood cells, Aviva is in late-stage discussions with several diagnostic companies, he said, and is hoping to announce at least one partnership within the next few months to develop the technology into a test kit.
“The potential market is the four million births in the US every year and all births worldwide, if the test can be provided inexpensively enough,” Lachenmeier said, and Aviva is hoping to keep the price around $250.
While Aviva is busy getting products on the market, it is already thinking about other uses of its intellectual property, which include one issued patent for individually addressable micro-electromagnetic unit array chips from Tsinghua University and 17 patent applications on other aspects of biochips and related technologies. For example, parts of the fetal cell isolation method could be applied to separate early metastatic cancer cells from normal cells to develop a tumor vaccine, Lachenmeier said.
Additional funding from institutional and angel investors could help Aviva develop chips for more applications. Aviva just received a $3 million bridge loan in February, part of a $11.5 million Series B follow-on financing round that the company is closing this summer. One of the lead investors of the current round is the Chinese Development Industrial Bank, which is based in Taiwan.