Miniaturisation of synthesis and screening in nanotiterplates: the concept of NanoSynTestTM

The NanoSynTestTM-system combines screening and synthesis in a highly integrated fashion. The central feature of the experimental system are nanotiterplates with a density of 100 wells/cm2 and a volume of roughly 0.1 μl each. The wells are equipped with a microsieve membrane for removal of liquids. Substance transfer of liquids and beads for solid phase synthesis is performed in the nl range with special adapted dispensers and sorting wafers. Thus the successfully performed adaptation of such tools to automated synthesis and screening workstations leads to experiments in synthesis, single bead analysis of synthesis products (IR spectroscopy, HPL-chromatography of single beads) and the fluometry of biological substances in nanotiterplates. These proof of principle experiments open up the way to a completely new and modular design of an integrated synthesis and screening facility based on nano- and microtechnology.

[1]  Johan Roeraade,et al.  Nanoliter Titration Based on Piezoelectric Drop-on-Demand Technology and Laser-Induced Fluorescence Detection , 1998 .

[2]  R. Pomeroy,et al.  Imaging applications for chemical analysis utilizing charge coupled device array detectors , 1993 .

[3]  A S Frangakis,et al.  Cryo-electron tomography of neurospora mitochondria. , 2000, Journal of structural biology.

[4]  W Chiu,et al.  Applications of a slow-scan CCD camera in protein electron crystallography. , 1994, Journal of structural biology.

[5]  L. A. Glover,et al.  CCD‐monitoring of bioluminescence during the induction of the cell wall‐deficient, L‐form state of a genetically modified strain of Pseudomonas syringae pv. phaseolicola , 1994, Letters in Applied Microbiology.

[6]  S. P. Fodor,et al.  Light-directed, spatially addressable parallel chemical synthesis. , 1991, Science.

[7]  Michael Gross Travels to the nanoworld , 1999 .

[8]  D. Ilsley,et al.  A microfluidic system for high‐speed reproducible DNA sizing and quantitation , 2000, Electrophoresis.

[9]  Dirk Tomandl,et al.  A Modified General Regression Neural Network (MGRNN) with new, efficient training algorithms as a robust 'black box'-tool for data analysis , 2001, Neural Networks.

[10]  J. Köhler,et al.  Nanotiterplates for combinatorial chemistry. , 2001, Journal of biotechnology.

[11]  George M. Whitesides,et al.  Patterning self-assembled monolayers using microcontact printing: A new technology for biosensors? , 1995 .

[12]  D. Pum,et al.  Crystalline bacterial cell surface layers (s layers): from supramolecular cell structure to biomimetics and nanotechnology. , 1999, Angewandte Chemie.

[13]  L. Benet,et al.  Effects of ketoconazole on the intestinal metabolism, transport and oral bioavailability of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor and a P450 3A, P-glycoprotein dual substrate, in male Sprague-Dawley rats. , 1998, The Journal of pharmacology and experimental therapeutics.

[14]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.

[15]  J. Köhler,et al.  Nanotiterplates for screening and synthesis , 1999 .

[16]  M. Eigen,et al.  Sorting single molecules: application to diagnostics and evolutionary biotechnology. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. , 1994, Journal of medicinal chemistry.

[18]  A. Schober,et al.  Accurate high-speed liquid handling of very small biological samples. , 1993, BioTechniques.

[19]  John A. Steinkamp,et al.  Flow cytometer for resolving signals from heterogeneous fluorescence emissions and quantifying lifetime in fluorochrome-labeled cells/particles by phase-sensitive detection , 1993 .

[20]  Manfred Eigen,et al.  Evolutionary molecular engineering based on RNA replication , 1984 .

[21]  D. J. Harrison,et al.  Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip , 1993, Science.

[22]  R. Pepperkok,et al.  A fully automated image acquisition and analysis system for low light level fluorescence microscopy , 1993 .

[23]  F. Oehlenschläger,et al.  Comparison of self-sustained sequence-replication reaction systems. , 1996, European journal of biochemistry.

[24]  A. Schober,et al.  Systemintegration of microsystems/chip elements in miniaturized automata for high-throughput synthesis and screening in biology, biochemistry and chemistry , 1997 .

[25]  A. Schober,et al.  Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer-bound isocyanate , 2003 .

[26]  K. Vrana,et al.  Fundamentals of DNA hybridization arrays for gene expression analysis. , 2000, BioTechniques.

[27]  F Schneider,et al.  A tissue-like culture system using microstructures: influence of extracellular matrix material on cell adhesion and aggregation. , 1999, Journal of biomechanical engineering.

[28]  Andreas Schwienhorst,et al.  Microsystems for independent parallel chemical and biological processing , 1995 .

[29]  F. Arnold,et al.  Combinatorial protein design: strategies for screening protein libraries. , 1997, Current opinion in structural biology.

[30]  Norio Miyaura,et al.  Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds , 1995 .