Here's a surprise. The blockbuster drugs of the future may already exist. Cancer cures, anti-Alzheimer's agents, gene treatments—all sitting safe as diamonds on the shelves of today's biotechnology and pharmaceutical research labs. The only problem? The millions of imitations glittering alongside them. All awaiting the jeweler's eye.

In today's pharmaceutical world, that may be a long wait. Finding the one truly valuable compound among swarms of cheap imitations involves large investments in buildings, equipment, and PhDs. Although many top-end laboratory tools have been automated, most steps in pharmaceutical screening still involve tricky and time-consuming hand transfers of small batches of samples and expensive reagents. As powerful new genetic and chemical techniques have created vast libraries of potentially useful compounds, this labor-intensive screening step has suddenly become the chief bottleneck of the biotech world.

In 1995, it also became the core business opportunity for Calvin Chow and his co-founders at Caliper Technologies.

"The chemists want this information desperately," says Chow, who worked side by side with chemists for ten years while developing biosensors at Molecular Devices Corporation. "But you can only do so many experiments in so much time. The clear path to reducing infrastructure and increasing throughput is microfluidics."

Using micromachining and micro-fabrication techniques borrowed from the semi-conductor industry, Chow and his colleagues can now mass produce stamp-sized pieces of glass or plastic embedded with networks of hair-width channels and wells. By applying electric current to the channels, they can coax liquids containing proteins, DNA, or cells through the maze. In this Caliper-patented LabChip™ technology, the delicate orchestration of voltage gradients within the network creates a system of nonmechanical pumps, valves, and gauges. What's more, as the fluids are precisely shuttled through the channels and wells, they can also be refined, separated, mixed, incubated, or analyzed.

"We mimic what the integrated circuits industry did 30 or 40 years ago," says Chow. "We took this roomful of test equipment and miniaturized and integrated it. Now we're providing access to millions of people. It's like going from the main-frame to the PC."

Chow thinks LabChip™ based technology will liberate biological research just as the desktop PC set loose the information technology revolution. He expects a blossoming of innovation not only in drug screening but also in basic biochemical research (such as DNA sequencing), medical diagnostics, forensics, and environmental testing.

In pursuing these applications, Caliper has adapted the "Intel-Inside" strategy of focusing on the chip engine while collaborating with partners such as Hewlett-Packard to construct and market the instruments. The first "LabChip™ Inside" desktop analyzer was shipped in September 1999, and Caliper has already struck alliances with Roche, Amgen, and Lilly for early access to its high-throughput screening systems.

What will it take for Caliper to succeed? Chow says the key will be integrating across disciplines. "It's not just the microfluidic technology that makes it work," he says. "It's also the chemistry, the manufacturing, the software, and the chip readers. You need a multidisciplinary skill set—the understanding of why your product will be useful to your customer. Engineers don't understand it all, and chemists don't understand it all. You need to blend the bioscience and the engineering."

For Chow, with his mechanical engineering gadget guru father and his chemist mother, such blending of scientific disciplines under one roof may seem a natural solution. The parental teamwork, in fact, may have inspired his current big-tent philosophy of bioscience. But where will he find all the broad-minded scientists to fill that tent?

"We like to hire Stanford graduates," he says, estimating that about 20 of the current 100 Caliper scientists were recruited from Stanford. "Stanford professors apply their teaching to the real world. It's a common sense as well as technical education, plus it stresses breadth. That package works well in a company that's multidisciplinary by design."

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