Interestingly, the thickness of the silicon resonator (~1 m) rendered these devices optically transparent, so that simultaneous optical and mass characterization of the cells was possible on the cantilever. To measure samples in suspension, high mass resolution can be achieved by embedding the microfluidic structures into the resonant element. and analysis of cells, tissue, and multicellular organisms. In the second part, we will describe two sensor approaches based on surface-plasmon resonance and mechanical resonators that have recently provided new characterization features for biological samples, while technological limitations for use in high-throughput applications still exist. applications.1,11,12 However, numerous limitations still exist in such systems, in particular for obtaining information or performing manipulation of the tested samples in real time. Several characterization methods, such as viability assays and biomarker quantification to assess either functionality or cytotoxicity are prevailingly performed off-chip and/or may be limited to end-point assays. The addition of on-line features and analysis/manipulation methods and the possibility to parallelize analysis and characterization of the samples would massively add to taking full advantage of these microphysiological model systems (Fig. 1). The integration of sensors within a culture platform usually entails higher sensitivity and temporal resolution, as analytes are not diluted. Moreover, high spatial resolution can be achieved through integration, so that heterogeneities in the concentrations of metabolites in the overall cell/tissue system can be detected.13 Open in a separate window Determine 1 Schematic representation of an integrated microphysiological system. Multiple interconnected organotypic microtissue models can be co-cultured Cloxacillin sodium in the platform to enable tissue-to-tissue interactions. The pumping and related flow mimics physiological shear stress on the tissues. The integrated sensors and actuators enable monitoring, characterization and manipulation of the tissue models and of potentially circulating cells. This review will present and discuss different classes of sensors and actuators, the use of which in MPSs has already been demonstrated, or which – in our opinion – offer great potential for integration in MPSs, also with respect to high-throughput analysis. As the field is still relatively young, standards for fluidic and electronic connections and for the design of such platforms are yet to be established. Definition of such standards will be imperative to ensure adoption of MPSs in industrial settings. For this review, we have decided to focus on methods that could be readily addressed and controlled by simple, parallelizable electronic systems and that offer the potential of straightforward integration with cell-culture environments. We will start with a description of electrical impedance spectroscopy and electrochemical biosensors and their applications with a broad range of biological samples. Although highly integrated microelectrode array (MEA) systems have been developed for and applications, we will not cover these systems here, as their application is limited to a few cell types, so-called electrogenic cells including mostly cardiomyocytes and neuronal cells.14,15 In Cloxacillin sodium the second part of this review, we will discuss surface-plasmon-resonance (SPR)-based sensors and mechanical micro- and nanosensors. Although these methods have so far shown limited parallelization potential, they have been successfully operated inside cell-culture environments and provide attractive characterization features for biological samples. Finally, with the exception of SPR, we have Cloxacillin sodium decided to not include optical methods, such as fluorescence-based RNF66 methods or bead-based assays, as the scope of this review would have otherwise become too broad. 2.?Electrical Impedance Spectroscopy Electrical impedance spectroscopy (EIS) is a non-invasive, label-free method to measure the dielectric properties of samples while applying an AC electrical field by means of electrodes. The work on Cloxacillin sodium impedance measurements of biological samples was pioneered by Hoeber and Fricke at the beginning of the 20th century.16,17 Following their approach, single-cell impedance measurements on Nitella cells were made in 1937 by Curtis and Cole.18 With the advent of microfluidic systems, integration of electrodes in microfluidic platforms has.