BioEd Online

A miniature chemistry set the size of a penny looks set to deliver faster, cheaper imaging agents for positron emission tomography (PET) scans, which are used to see inside patients' bodies.

The microfluidic chip uses a tiny network of channels to shuttle chemicals around, and has valves and purification filters to perform a sequence of chemical steps. The result can produce a chemical that is crucial for PET scans much more quickly and with fewer reagents than a standard lab. This should make scans simpler and cheaper for hospitals.

Microreactors are not a new idea, and are increasingly being used in research laboratories. But many rely on a continuous flow of material from one end of a miniature pipe to the other, without valves and filters. These continuous flow reactors are plagued by cross-contamination of reagents from different chemical steps, says Hsian-Rong Tseng, a pharmacologist at the University of California, Los Angeles, and part of the team that developed the device. This is a significant barrier to using such chips to make pharmaceuticals or other complex chemicals, he says.

The valve-based chip is so versatile that it could become one of the first microreactors in widespread use outside the research lab, says Tseng.

"It's an excellent demonstration of the potential of integrated microfluidics," says Klavs Jensen, a chemical engineer at the Massachusetts Institute of Technology. "It should have considerable impact."

Sweet talk

The chip produces 2-deoxy-2[18F]fluoro-D-glucose (FDG), the most widely used radioactive imaging agent for medical PET scans. This chemical is normally produced by commercial synthesizers, each costing about US$140,000, which churn out 10 to 100 doses in a single run that takes 50 minutes.

Traditional production of the agent is limited to special facilities housed in major universities, which ship out fresh batches of the chemical each day. FDG is then given to patients, where it mixes in the body like normal glucose. The tracer can be mapped by a PET scanner, showing the layout of blood vessels and surrounding tissue in the patient.

With a supply of raw radioactive fluoride ions, the microchip can produces very pure FDG in about 14 minutes. In tests, the chip produced several doses of FDG on demand, which were then used to image a laboratory mouse.

"This technology will give centres more flexibility in meeting patient needs," says Tseng. The research is published today in Science¹.

Efficient chips

Making these polymer chips is so simple that with the help of computer-aided design it can take just two days to create a chip to run a particular sequence of chemical reactions, and the average cost is just $10 apiece, says Tseng.

The chips are being developed for commercial use by Siemens Medical Solutions, headquartered in Malvern, Philadelphia, along with the Fluidigm Corporation, based in San Francisco. One of Fluidigm's founders is Stephen Quake, a co-author on the Science paper and chemist from Stanford University, California, who Tseng credits with developing the method for producing chips with valves.

As the chemical products from the chips have not yet been tested on humans, it may be three years before they see regular use in medical centres, says Tseng.