New kinetic strategy for extracting FDG transport and uptake information in microfluidic multi-chamber cell culture chip coupled with PSAPD

Objectives A microfluidic cell culture chip coupled with PSAPD (μF-PSAPD) has been developed to give continuous measurements of radioactivity in individual chambers that can be used to provide useful biological information of cells. New strategies of controlling the infusion and tracer level are needed to provide reliable estimates of the parameters.

Methods A switching strategy (SS) was conceived that consists of multiple medium-infusion cycles, each of which has a tracer incubation (TI) period followed by a background-removed (BR) period (tracer-free medium). Performance of SS was evaluated by computer simulation and by experiments on MF-PSAPD. In simulation, realistic FDG kinetics of 12 cycles of TI and BR periods (5 min each) corresponding to 4 different sets of k values were simulated. Then, k values were estimated by regressing the kinetics with the FDG model. Results of 120 realizations were obtained and compared to those of constant infusion. For experiments, SS was adopted on a μF-PSAPD once with 4 cell lines (U87, P8, CaP8, B16) in different chambers, and in another with 3 medium glucose levels.

Results Simulations showed that the estimated k values with SS have large reduction in %CV compared to those of constant infusion, with the largest reduction in Ki from 116 to 12. For experiments, measured kinetics was well fitted by the model (R-square=0.9999 on average). Ranks of Ki estimate were CaP8> B16 > P8>U87. Ki was inversely related to glucose level as expected.

Conclusions The new strategy of tracer infusion provides reliable estimates of FDG Ki in μF-PSAPD. Optimization of the cyclic periods is expected to improve parameter estimation further.