Reaction in Hand: Microreactor produces radioactive probe in a jiffy

A miniature chemical reactor that whips up a diagnostic tool could widen the availability of positron-emission tomography (PET) scans, say the reactor’s inventors.

HOT CHIP. Food dyes illustrate tunnels, pumps, and valves in this microreactor, which makes nanogram amounts of a PET probe. Penny shows scale. Science

PET uses radioactive molecules to image metabolism or other physiological functions. The most commonly administered probe is a radioactive version of glucose that reveals tumors, which take up more of this nutrient than regular cells do.

Making radioactive probes requires expensive machinery. Radioactive elements are generated by particle accelerators known as cyclotrons. Commercial synthesizers costing about $140,000 then chemically incorporate the radioelement into a desired molecule.

Furthermore, probe production must be quick because the activity of their radioactive elements decreases rapidly. One half of a quantity of fluorine-18 decays in 110 minutes, but commercial synthesizers take about 50 minutes to make the PET-glucose probe that contains fluorine-18.

To come up with a faster, more versatile synthesizer, a multi-institute research team from California designed a silicone microchip with a pattern of tunnels, valves, and pumps. The pattern permits a series of reactions to take place sequentially in closed regions of the chip, preventing cross-contamination of reactants. A computer controls the order of the reactions and pumps in reagents through tubing connected to the chip.

The five-step chemical reaction that synthesizes the glucose probe requires several different solvents. Vapors can escape through the chip’s porous silicone, so the researchers can heat fluid in the chip to burn off one solvent before introducing another, says Stephen R. Quake of Stanford University. He and his colleagues describe their device in the Dec. 16 Science.

A standard clinical dose of the radioactive glucose probe has an activity of 10 millicuries (mCi). With their first microreactor, the researchers made 190 microcuries of the material in 14 minutes. But a second-generation chip synthesized 1.74 mCi of the probe in under 20 minutes. That’s more than enough to image a tumor in a mouse.

With additional chip designs, the production of multiple radioactive probes will be as easy as swapping chips, say Quake and coauthor Hsian-Rong Tseng of the University of California, Los Angeles. The low cost of the materials that go into the system, which is being explored for commercialization, should mean more medical facilities can make their probes on-site, says Tseng.

“You have to be within striking distance of a cyclotron,” says Quake, but these machines are fairly well distributed across the United States.

The system offers the potential for “radioisotopes on demand, customized to biologically relevant molecules,” says mechanical engineer Todd Thorsen of the Massachusetts Institute of Technology. He notes that the microchip could benefit basic research as well as medical diagnosis.

But the silicone material does limit the types of reactions the chip can perform, cautions Quake. Some widely used solvents would cause the silicone to swell and close off the tunnels.

Aimee Cunningham

Aimee Cunningham is the biomedical writer. She has a master’s degree in science journalism from New York University.

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