Disposable micro-fluidic biosensor array for online parallelized cell adhesion kinetics analysis on quartz crystal resonators

摘要

In this contribution we present a new disposable micro-fluidic biosensor array for the online analysis of adherent Madin Darby canine kidney (MDCK-II) cells on quartz crystal resonators (QCRs). The device was conceived for the parallel cultivation of cells providing the same experimental conditions among all the sensors of the array. As well, dedicated sensor interface electronics were developed and optimized for fast spectra acquisition of all 16 QCRs with a miniaturized impedance analyzer. This allowed performing cell cultivation experiments for the observation of fast cellular reaction kinetics with focus on the comparison of the resulting sensor signals influenced by different cell distributions on the sensor surface. To prove the assumption of equal flow circulation within the symmetric micro-channel network and support the hypothesis of identical cultivation conditions for the cells living above the sensors, the influence of fabrication tolerances on the flow regime has been simulated. As well, the shear stress on the adherent cell layer due to the flowing media was characterized. Injection molding technology was chosen for the cheap mass production of disposable devices. Furthermore, the injection molding process was simulated in order to optimize the mold geometry and minimize the shrinkage and the warpage of the parts. MDCK-II cells were cultivated in the biosensor array. Parallel cultivation of cells on the gold surface of the QCRs led to first observations of the impact of the cell distribution on the sensor signals during cell cultivation. Indeed, the initial cell distribution revealed a significant influence on the changes in the measured acoustic load on the QCRs suggesting dissimilar cell migrations as well as proliferation kinetics of a non-confluent MDCK-II cell layer.