The use of microfluidics for the purification of medical radioisotopes

Abstract

To obtain radionuclides for medical use from an isotope generator, mother and daughter nuclides need to be separated. In contrast to adsorption-based generators where the mother nuclide is retained on a static column, in liquid generators both mother and daughter nuclides are in solution and need to be separated via extraction. Microfluidic techniques are promising for the extraction process because mass transfer is very efficient and in theory the laminar two-phase flow in the microchannel can be easily separated at the end.

The generator of interest in this thesis is the W-188/Re-188 generator. However, some work also concerns the chemical similar Mo-99/Tc-99m generator and the Lu-177m/Lu-177 generator.

The start objective was to find a less water miscible replacement for the commonly applied organic phase methyl ethyl ketone (MEK) in the W-188/Re-188 generator, since with this system precipitation was observed previously in the microchannel. Several organic phases have been tested for precipitation, but also for their extraction efficiencies and abilities to separate rhenium from tungsten. The best results were observed for 0.2 M Aliquat 336 in 1,3-diisopropylbenzene, an organic phase that shows no precipitation, has suitable wetting behaviour in the microchannel and an even higher extraction efficiency than MEK.

Another issue addressed in this thesis is the incomplete phase separation at the Y-splitter (end) of the channel. Either some aqueous phase leaves through the organic outlet or some organic phase leaves through the aqueous outlet. One possible reason for the leakage is the uniform surface of both outlets, and therefore the preferred wetting of the hydrophilic glass wall of the microchannel with one phase. Coating one side of the microchannel hydrophobically showed that the leakage can be stopped. The effects of radiation on the coating have been investigated using an external gamma source and a threshold of 5 kGy before deterioration was found.

An even easier method to achieve complete phase separation is the use of a membrane separator.
Here, two phases are combined in simple 0.5 mm tubing in droplet fashion before being separated by a membrane. With the above mentioned organic phase, an extraction efficiency of 95% was reached within 5.3 minutes contact time. This is considerably longer than the typical contact time in the microchannel (in the order of seconds), but the total handling time was reduced from over 3 hours (with a microchannel) to 16 minutes by using a membrane separator. For lutetium, an extraction efficiency of 99% was reached after 2 minutes contact time, reducing the total handling time by a factor of 2.5 compared to the conventional method.