Relying on modified caulking rubber and the smarts of a 31-year old Caltech biophysicist, fledgling microfluidics maker Fluidigm has created a biochip that it believes will stimulate the flow of innovation in life sciences and other fields.
“What the integrated circuit did for electronics we believe this platform will do for fluidics,” said Fluidigm CEO Gajus Worthington.
The platform, called multilayer soft lithography, was created in the late 1990s by Caltech physicist Stephen Quake to control the flow of miniscule amounts of fluid for an experiment. Quake and his colleague Marc Unger took squares of transparent polydimethylsiloxane and made a multi-layer sandwich out of them with networks of microchannels. The two layers, with air pockets in between, allowed the scientists to form microvalves that could be squeezed closed by pumping controlled amounts of air into the adjoining air channels, or opened by stopping the air pressure.
“What these guys have developed are the world’s smallest mechanical valves and pumps,” said Todd Krueger, Fluidigm’s vice president of corporate development and finance.
These valves allow for the fluid flow to be started and stopped more precisely than capillary electrophoresis, the method of moving fluids through microchannels used by microfluidics leaders Caliper and Aclara, Krueger said.
Also, while the anode-cathode mechanism can limit fluid movement in electrophoresis systems to linear circuits, these valves and pumps allow fluids to be moved in circles, allowing for mixing, said Krueger. “This means you can miniaturize processes such as receptor-ligand binding and hybridization,” he said.
The fluidic chips are produced using a mold made from a silicon wafer covered with photoresist and etched with channels. This mold is reusable, and the rubber material for the chips is significantly cheaper than silicon, making it possible to produce cheap custom chips for researchers in days rather than weeks.
In April 2000, Quake and his colleagues published an article on their findings in Science.
Fluidigm, which just changed its name from Mycometrix, has since developed the chips to the point where there are 600 valves and pumps on a chip, and more than two layers of channels. The company is marketing the chips for use in cell sorting, a process that it claims electrophoresis methods cannot do well due to the potential for the electricity to damage the cell. They also expect the chips will be used for sequencing; SNP detection; protein separation; crystallization and detection; sample preparation; and single molecule analysis. In addition, they believe that the chips will be used in other areas where miniaturization of experiments is important, such as the chemical and power industry.
One limitation of these chips is that they cannot work at temperatures above 200 degrees centigrade. Another potential problem, which could affect some protein experiments, is that some fluids move better through rubber than others.
In the next quarter, Fluidigm is preparing to ship a starter kit for researchers who want to develop applications for the technology. The kit includes chips and pipettes to add fluid to the chips, a Windows-based software platform called Fluid Architect that allows researchers to design their own custom chips within certain frameworks, and a chip control box that allows researchers to control the flow of fluid into the chips. The chips can be observed through a standard microscope, although Fluidigm is looking for instrumentation partners to custom-design special equipment for viewing the chips.
Meanwhile, Fluidigm is in the midst of its third fundraising round. Having raised $14.5 million so far, the company hopes to raise quite a bit more money — “in the double digits” — in order to fuel efforts to commercialize the technology. Additionally, the company is planning to announce a development partnership for its technology within the next several weeks.
“We see a lot of enthusiasm for technology from both the user standpoint and the funding standpoint,” said Krueger.