Experimental system to detect a labeled cell monolayer in a microfluidic environment.

Abstract

To investigate the feasibility of detecting a living cell monolayer labeled with gadoterate (Gd-DOTA) in a microfluidic environment, by micromagnetic resonance imaging (MRI) in a 2.35T small-animal system. The development of new targeted contrast agents (CAs) requires proof-of-concept studies in order to establish the detectability of the CA and to predict the role of biodistribution in its uptake mechanisms. A promising approach is to carefully mimic the in vivo pharmacokinetic context with reduced experimental complexity compared to in vivo situations. A dedicated experimental system was built by combining a microfluidic slide and a radiofrequency probe based on a 6 mm diameter multiturn transmission-line resonator. Adherent KB cells were incubated with different concentrations of Gd. MRI data were acquired at 2.35T with a 3D gradient echo and a resolution of 12.4 μm perpendicular to the cell layer. The longitudinal relaxation rate, R1 , was measured as a function of the amount of Gd internalized by the cells. R1 measurements for different Gd concentrations per cell were performed using data with an signal-to-noise ratio (SNR) of 100. Relaxation-rate variations ΔR1 of 0.035 s(-1) were measured. A quenching effect was observed at Gd concentrations above 20 fmol/cell. Our results suggest that this dedicated experimental system is suitable for specifically assessing new high-relaxivity targeted CAs under real-time uptake conditions.