title: Blood compatible microfluidic system for pharmacokinetic studies in small animals.
abstract: New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection.
authors.affiliation: Nanofabrication and Nanocharacterization Research Center, Department of Electrical and Computer Engineering, Université de Sherbrooke, 2500 Bd Université, Sherbrooke, QC, J1K 2R1, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Convert
authors.forename: Frédérique Girard
authors.initials: FG
authors.lastname: Baril
authors.forename: Vincent
authors.initials: V
authors.lastname: Boisselle
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pratte
authors.forename: Réjean
authors.initials: R
authors.lastname: Fontaine
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.forename: Paul G
authors.initials: PG
authors.lastname: Charette
authors.forename: Vincent
authors.initials: V
authors.lastname: Aimez
mesh_terms: D000818:Animals; D001769:Blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D004566:Electrodes; D004867:Equipment Design; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008422:Materials Testing; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon; D014867:Water / Q000737:chemistry
chemical_list: D019275:Radiopharmaceuticals; D014867:Water; D019788:Fluorodeoxyglucose F18