Automated multiparametric platform for high-content and high-Throughput Analytical screening on living cells

摘要

Addressing the increasing biomedical and pharmacological interest in multiparametric screening assays, a concept has been developed, which integrates multiparametric, bioelectric, and biochemical sensors for the analytical monitoring of intra- and extra cellular parameters and an automated imaging microscope for high-content screening into a single embedded platform. Utilizing a topology of distributed intelligences and hardware-based synchronization, the platform concept allows precisely timed and synchronized operation of all integrated platform components. The concept is highly modular, and its design-inherent versatility allows a multitude of platform configurations suiting widely differing user requirements. They include the future integration of probe-manipulation systems such as climate control, fluidic systems, and automated probe placement. Hardware-level synchronization is achieved with a newly developed digital signal processor based "Integration Control Unit," which runs a real-time environment and provides standard electrical interfaces to connect to other platform components. The platform can be operated "online" by user-interactive control or precisely timed and completely automated within high-throughput applications by executing experiment protocols that have been composed in advance. Possible applications of the integrated platform employ a parallel optical and sensory monitoring of extra- and intracellular parameters, yielding detailed insight into cellular functions and intercellular interrelations. Thus, the proposed automated platform may develop into an enabling technology for future screening assays, especially in the field of pharmacological drug screening. Note to Practitioners-One trend in screening applications is to measure an increasing number of cellular parameters in parallel (high-content screening) to obtain a comprehensive view on the investigated cellular process. This motivated us to develop a platform, which provides simultaneous acquisition of multisensor and fluorescence microscopic data. Since both techniques are well established in numerous screening applications, we hope that this new combination stimulates the development of new assays (e.g., in pharmacological drug screening, clinical diagnostics, or environmental -monitoring). Since prototypes for high-content screening are available, we are interested in cooperation with scientists working on assay development.