High efficiency microfluidic beta detector for pharmacokinetic studies in small animals

New radiotracers are continuously being developed to improve diagnostic efficiency using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). The characterization of their pharmacokinetics requires blood radioactivity monitoring over time during the scan and is very challenging in small animals because of the low volume of blood available. In this work, a prototype microfluidic blood counter made of a microchannel atop a silicon substrate containing PIN photodiodes is proposed to improve beta detection efficiency in a small volume by eliminating unnecessary interfaces between fluid and detector. A flat rectangular-shaped epoxy channel, 36 μm×1.26 mm 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 few micrometers of epoxy floor layer between the fluid and the photodiode sensitive surface. This geometry leads to a quasi 2D source, optimizing geometrical detection efficiency that was estimated at 41% using solid angle calculation. CV–IV measurements were made at each fabrication step to confirm that the microchannel components had no significant effects on the diodes’ electrical characteristics. The chip was wire-bonded to a PCB and connected to charge sensitive preamplifier and amplifier modules for pulse shaping. Energy spectra recorded for different isotopes showed continuous beta distribution for PET isotopes and monoenergetic conversion electron peaks for 99mTc. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 26% to 33% for PET tracers (18F, 13N, 11C, 68Ga) and more than 2% for 99mTc. Input functions were successfully simulated with 18F, confirming the setup’s suitability for pharmacokinetic modeling of PET and SPECT radiotracers in animal experiments. By using standard materials and procedures, the fabrication process is well suited to on-chip microfluidic functionality, allowing full characterization of new radiotracers.