Microsystems recently have been introduced as tools for screening in modern chemistry, biochemistry and biology. It has been shown that new microsystems can be implemented in the biomedical laboratory by using the microsystemic approach for the sample carrier -the miniaturized microtiter plate (''the nanotiter plate'') -or the production of nanodroplets with ink jetters and to integrate those systems in macrodevices like xyz tables and detection devices like CCD-cameras. We show in this paper that decisive problems of the approach -the evaporation problem and the problem of chemical/biochemical/biological compatibility of the assays and the used materials can be solved successfully. It is possible to realize chemical synthesis in miniaturized flow systems and to perform isothermal amplification of RNA in silicon wafers. Furthermore real high throughput screening with in vivo systems can be performed and all relevant parameters as evaporation, pipetting and detection can be controlled on reasonable time scales.
Microstructured silicon wafers were employed as miniaturized solid-phase reaction vessels as well as miniaturized micro titer plates. Employing piezoelectric drop-on-demand liquid jets, a combinatorial library of 256 Peptides was synthesized on single beads. The synthesis protocol was associated to the location in the silicon nano-well arrangement. Products were photolytically cleaved in the same well that was used for synthesis and subsequently interrogated for thrombin inhibition in a homogeneous competition assay. The assay procedure was based on drop-on-demand liquid delivery and laser induced fluorescence imaging. The novel format proved useful for the integration of both synthesis and screening into one platform, a prerequisite for an iterative, evolutionary approach towards drug discovery.
In biotechnics microsystems have been introduced primarily for analytical purpose in the past few years. Recently miniaturised microtiterplates, so called nanotiterplates, as efficient tools in screening have been discussed.In a case study we demonstrate the application of cell-free translation or transcription/translation and nucleic acid amplification in such nanotiterplates.The results show the potential range of applications of nanotiterplates for biotechnology even for biochemical systems, which have not been discussed as miniaturisable in screening.
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