Microfluidic beta and conversion electron radiation detector for preclinical pharmacokinetic studies with PET and SPECT radiotracers

The characterization of new radiotracer pharmacokinetics in small animals is very challenging because of the small volume of blood available. For this purpose, a microfluidic blood counter prototype made of a microchannel on silicon containing PIN photodiodes was proposed to improve beta detection efficiency in a small volume by eliminating all unnecessary interfaces between blood and detector. In this work, a new optimized configuration with improved geometrical detection efficiency and new dedicated electronics have been investigated for the detection of positron-emitting radiotracers, and also for ^99mTc based radiotracers, detected via their low-energy (<; 140 keV) internal conversion electrons. A flat rectangular epoxy channel with a 42 × 780 μm² cross section and 31.5 mm in length was microfabricated over a die containing an array of 2 × 2 mm² PIN photodiodes leaving only a 5-μm epoxy floor layer between the blood and the photodiode sensitive surface. CV-IV measurements were made at each fabrication steps to detect any detrimental effects of the microchannel on the diodes electrical characteristics. The microfluidic chip was wire bonded to a gold plated custom made PCB and connected to a custom-made signal processing board for pulse shaping and amplification. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 35 to 41% for PET tracers (¹⁸F, ¹¹C) and more than 4% for ^99mTc. Energy spectra recorded for different isotopes and calibrated with ¹³³Ba and ²⁴¹Am solid sources showed typical beta distribution spectra for PET isotopes and a characteristic peak corresponding to conversion electrons for ^99mTc. Input functions were successfully simulated with ¹⁸F and ^99mTc, confirming that the setup is suitable for pharmacokinetic modeling of PET and SPECT radiotracers i- - n animal experiments. The fabrication process uses standard materials and procedures and would allow the addition of microfluidic functionalities on-chip to enable full characterization of new radiotracers.