Miniaturisation of synthesis and screening in nanotiterplates: The concept of NanoSynTest™

Microsystem Technologies

Volumn 10, Issue 4, 2004, Pages 281-292

  Schober, A ^a,b   Schlingloff, G ^a,b   Gross A ^a,b   Henkel, T ^a,b   Albert, J ^a,b   Mayer, G ^a,b   Wurziger, H ^c   Doring M ^d   Tietz, H ^e  

^a LEIBNIZ INSTITUTE OF PHOTONIC TECHNOLOGY   (Germany)

^b Merck KGaA ^*  (Germany)

^c MERCK KGAA   (Germany)

^d Microdrop GmbH   (Germany)

^e Tietz Video/Image Proc Systems GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BIOTECHNOLOGY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; INFRARED SPECTROSCOPY; MONOLAYERS; SCREENING; SELF ASSEMBLY; SYNTHESIS (CHEMICAL);

FLUOMETRY; MINIATURIZATION TECHNOLOGY; NANOTITERPLATES;

NANOTECHNOLOGY;

EID: 3042589247     PISSN: 09467076     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00542-003-0328-5     Document Type: Article

References (127)

1. a) Drexler KE (1992) Nanosystems. John Wiley and Sons.
2. b) Gross M (1999) Travels to the Nanoworld. Plenum Trade
3. c) Merkle RC (1999) Biotechnology as a route to nanotechnology. Tibtech 17: 271-274. "Innovationsschub aus dem Nanokosmos"
4. d) Bachmann G (1998) "Technologieanalyse". VDI- Technologiezentrum Zukünftige Technologien Düsseldorf
5. Saluz HP (ed.) (1999) Microsystem technology: a powerful tool for biomolecular studies in Bio-methods, Vol.10. Birkhäuser Verlag Basel
6. a) Fodor SPA; Read JL; Pirrung MC; Stryer L; Lu AT; Solas D (1991) Light-directed, spatially addressable parallel chemical synthesis. Science 251: 767-773.
7. b) Lipshutz RJ; Morris D; Chee M; Hubbell E; Kozal MJ; Shah N; Shen N; Yang R; Fodor SPA (1999) Using oligonucleotide probe arrays to acess genetic diversity. In Saluz HP (ed.), Microsystem Technology: a Powerful Tool for Biomolecular Studies, pp. 241-254.
8. c) Henkel Th; Klenz U; Mayer G; Schober A; Köhler M (2000) In-situ synthesised nanoporous spot arrays for fast working chip assays. International Meeting on Microreaction Technology, Atlanta, Georgia, USA.
9. d) Whitesides GM; Mathias JP and Seto CT (1991) Molecular self assembly and nano-chemistry. Science 254: 1312-1319.
10. e) Mrksich M; Whiesides GM (1995) Patterning self assembled monolayers using microcontact printing: a new technology for biosensors? Trends Biotechnol 13: 228-235
11. a) Harrison DJ; Fluri K; Seiler K; Fan Z; Effenhauser CS; Manz A (1993) Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science 261: 895-897.
12. b) Neuhoff V (2000) Electrophoresis 21.
13. c) Litborn E; Emmer A; Roeraade J (2000) Parallel reactions in open chip-based nanovials with continuous compensation for solvent evaporation Electrophoresis 21(1): 91-99
14. a) Northrup MA; Ching MT; White RM; Watson RT (1993) DNA amplification in a microfabricated reaction chamber. In: Transducers 1993. Seventh International Conference on Solid State Sensors and Actuators, Yokohama, Japan, pp. 924-926. ISBN 4-9900247-2-9, 924-927.
15. b) Mueller O; Hahnenberger K; Dittmann M; Yee H; Dubrow R; Nagle R; Iisley D (2000) A microfluidic system for high-speed reproducible DNA sizing and quantitation. Electrophoresis 21(1): 128-134
16. a) Freeman WM; Robertson DJ; Vrana KE (2000) Fundamentals of DNA hybridization arrays for gene expression analysis. BioTechniques 29: 1042-1055.
17. b) Singh-Gasson S; Green RD; Yue Y; Nelson C; Blattner F; Sussman MR; Cerrina F (1999) Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat Biotechnol 17: 974-978.
18. c) Gerhold D; Rushmore T; Caskey CT (1999) DNA chips: promising toys have become powerful tools. Trends Biochem Sci 24(5): 168-173.
19. d) Fodor SPA; Read JL; Pirrung MC; Stryer L; Lu AT; Solas D (1991) Light-directed, spatially addressable parallel chemical synthesis. Science 251: 767-773.
20. e) Lipshutz RJ; Morris D; Chee M; Hubbell E; Kozal MJ; Shah N; Shen N; Yang R; Fodor SPA (1999) Using oligonucleotide probe arrays to acess genetic diversity. In: Saluz HP (ed.), Microsystem Technology: a Powerful Tool for Biomolecular Studies, pp. 241-254
21. a) Burns MA; Mastrangelo CH; Sammarco TS; Man FP; Webster JR; Johnson BN; Foerster B; Jones D; Fields Y; Kaiser AR; Burke DT (1996) Proc. Natl. Acad. Sci. USA 93; 5556-5561.
22. b) Schober A; Günther R; Schwienhorst A; Döring M; Lindemann B (1993) accurate high speed liquid handling of very small biological samples. Biotechniques 15(2).
23. c) Schober A; Schwienhorst A; Köhler JM; Fuchs M; Günther R; Thürk M (1994) Microsystems for independent parallel chemical and biological processing. Microsystems Technologies, Berlin, pp. 381-390.
24. d) Schober A; Schlingloff G; Thamm A; Vetter D; Tomandl D; Gebinoga M; Kiel HJ; Scheffler Ch; Döring M; Köhler JM; Mayer G (1996) Systemintegration of microsystems/chip elements in miniaturized automata for high-throughput synthesis and screening in biolo-gy, biochemistry and chemistry Microsystems,
25. e) Köhler M; Mayer G; Schulz Th; Schober A (1996). Chip elements for combinatorial chemistry, fluid processing and PCR Microsystems.
26. f) Schober A; Schwienhorst A; Köhler JM; Fuchs M; Günther R; Thürk M (1995) Microsystems for independent parallel chemical and biologica processing. Microsyst Technol 1(4): 168.
27. g) Schober A; Schlingloff G; Thamm A; Tomandl D; Gebinoga M; Kiel HJ; Scheffler Ch; Döring M; Köhler JM; Mayer G (1997) Systemintegration of microsystems/chip elements in miniaturized automata for high-throughput synthesis and screening in biology, biochemistry and chemistry. Microsyst Technol 4: 35
28. a) Zhao H; Arnold FH (1997) Combinatorial protein design: Strategies for screening protein libraries Currnet Opinions Struct Biol 7:5.480-485.
29. b) Hertzberg RP; Pope AJ; (2000) Curr Opin Chem Biol 4(4): 445-451
30. Schober A; Schlingloff G; Thamm A; Kiel HJ; Tomandl D; Gebinoga M; Döring M; Köhler JM; Mayer G (1997) Systemintegration of microsystems/chip elements in miniaturized automata for high-throughput synthesis and screening in biology, biochemistry and chemistry. Microsyst Technol 4: 35
31. a) Schober A; Schlingloff G; Tomandl D; Köhler JM; Mayer G; Wuchty S; Deppe H; Diefenbach B; Wurziger H (1998) Chemical and biochemical synthesis and screening in silico. Microsystems. Micro System Technologies, VDE Verlag, pp. 451.
32. b) Gebinoga M; Schlingloff G; Thamm A; Beck Ch; Schober A (2001) Biochemical Synthesis in microstructred silicon wafer. Z f Phy Chem 216: 91-102.
33. c) Hempel R; Wirsching F; Schober A; Schwienhorst A (2001) A new reporter gene system suited for cell-free protein synthesis and high-throuput screening in small reaction volumes. Anal Biochem 297: 177-182.
34. d) Vetter D; Thamm A; Schlingloff G; Schober A (2002) Single bead synthesis of oligopeptides on silicon. Molecular Diversity 5(3): 111-116
35. Schober A; Schlingloff G; Tomandl D; Köhler JM; Mayer G; Groß A; Albert J; Henkel Th; Willems A; Deppe H; Diefenbach B; Wurziger H (2001) NanoSynTest™: An integrated platform for chemical synthesis and biological testing in nanotiterplates. Microsystems, 151-156
36. a) Gallop MA; Barrett RW; Dower WJ; Fodor St PA; Gordon EM (1994) Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J Med Chem 37(9): 1233-1251.
37. b) Gordon EM; Barrett RW; Dower WJ; Fodor St PA; Gallop MA (1994) Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies and future directions. J Med Chem 37(10): 1385-1401.
38. c) DeWitt AW; Czarnik (1995) Automated synthesis and combinatorial chemistry current opinion in biotechnology 6: 640-645.
39. d) Dekker M (1997) High-throughput screening of bioactive substances. M. Dekker inc. New York Hong Kong Basel.
40. e) Burbaum JJ; Sigal NM (1997) New technologies for high-throughput screening. Current Opinion Chem Biol 1: 72-78.
41. f) Houston JG; Banks M (1997) The chemical-biological interface: developments in automata and miniaturized screening technology. Current Opinion Biotechnol 8: 734-740.
42. g) Zhao H; Arnold FH; (1997) Combinatorial protein design: Strategies for screening protein libraries. Current Opinions Struct Biology 7:S.480-485.
43. h) Litborn Stjernström M; Roeraade J (1998) Nanoliter Titration based on piezoelectric drop-on-demand technology and laser induced fluorescence detection. Anal Chem 70: 4847-4852
44. Köhler JM; Mayer G; Schulz Th; Schober A (1996) Chip elements for combinatorial chemistry, fluid processing and PCR. Microsyst Technolo 1(4): 202
45. Döring M; Schober A (1997) Vorrichtung und Verfahren zum genauen Dosieren und Umsetzen von kleinen Flüssigkeitsmengen DE 197 42 005 A
46. Schlingloff G (in preparation)
47. Henkel Th; Albert J; Bräutigam A; Mayer G; Schober A (2000) Druckimpulsgesteuerter Kapillardispenser. DE 100 10 208.5
48. Döring M; Mayer G; Schlingloff G; Schober A (1998) Probensortier-, Übergabe- und Aufnahme-vorrichtung für kleine Mikroperlen und Verfahren zu deren Betrieb. Patentanmeldung 198 50 233.8
49. Mayer G; Schober A; Köhler JM (2001) Nanotiterplates for combinatorial Chemistry. Rev Molecular Biotechnol 82(2): 137-159
50. a) Eigen M; Rigler R (1994) Sorting single molecules: application to diagnostics and evolutionary biotechnology. Proc Natl Acad Sci USA 91: 5740-5747.
51. b) Koppel DE; Morgan F; Cowan AE; Carson JH (1994) Sacnning concentration correlation spectroscopy using the confocal laser microscope. Biophys 66: 502-507
52. Sweedler JV; Bilhorn RB; Epperson PM; Sims GR; Denton MB (1988) High performance charge transfer devices. Anal Chem A40 4: 282-291
53. a) Arndt-Jovin DJ; Robert-Nicoud M; Kaufman SJ; Jovin TM (1985) Fluorescent digital imaging microscopy in cell biology. Science 230(4723): 247-256.
54. b) Hiraoka Y; Agard DA; Sedat JW (1987) The use of charge coupled devices for quantitative optical microscopy of biological structures. Science 231: 36-41
55. a) Steinkamp JA; Joshida TM; Martin JC (1993) Flow cytometer for resolving signals from heterogeneous fluorescence emissions and quantifying life time in fluorochrome-labeled cells/particles by phase-sensitive detection. Rev Sci Instrum 64(12): 3440-3450.
56. b) Kubota F; Kusuzawa H; Kosaka T; Nakamoto H (1995) Flow cytometer and imaging device used in combination. Cytometry 21: 129-132
57. a) Herr St; Bastian Th; Pepperkok R; Boulin Ch; Ansorge W (1993) A fully automated image acquisition and analysis system for low light level fluorescence microscopy. Meth Molecular Cellular Biology 4: 164-170.
58. b) Ambroz M; MacRobert AJ; Morgan J; Rumbles G; Foley MSC; Philipps D (1994) Time-resolved fluorescence spectroscopy and intracellular imaging of disulphonated aluminum phthalocyanine. J Photochem Photobiol B: Biol. 22: 105-117
59. a) Highett M.I; D.J. Rawlins; P.J. Shaw (1993) Different patterns of rDNA distribution in Pisum sativum nucleoi correlate with different levels of nucleor activity. J Cell Sci 104: 843-852
60. b) Hayes StJ; Hinchliffe StA; Pope JD; Eccles P; Khine MM; Kaschula ROC; Sampedro A; van Velzen D (1995) Ploidy analysis on Wilms tumor touch imprints using ethidium bromide and automated image analysis integrated confocalscanning microscopy. Virchows Arch 427: 101-104
61. a) Maier E; Crollius HR; Lehrach H (1994). Hybridization techniques on gridded high density DNA and in sito colony filters based on fluorescence detection. Nucleic Acids Research. 22(16): 3423-3424
62. b) Lengauer Ch; Speicher RM; Popp S; Jauch A; Taniwaki M; Nagaraja R; Riethman HC; Donis-Keller H; D'Urso M; Schlessinger D; Cremer Th (1993) Chromosomal bar codes produced by multicolor fluorescence in situ hybridization with multiple YAC clones and whole chromosome painting probes. Human Molecular Genetics. 2(5): 505-512
63. a) White MRH; Morse J; Boniszewski ZAM; Mundy CR; Brady MAW; Chriswell DJ (1990) Imaging of firefly luciferase in single mammalian cells using high sensitive charge coupled device cameras. Technique 2(4): 194-201.
64. b) Waterhouse RN; Glover LN (1994) CCD monitoring of bioluminescence during the induction of cell wall-deficient, L-form state of a genetically modified strain of Pseudomonas syringae pv.phaseolicola. Lett Appl Microbiol 19: 88-91
65. a) Earle CW; Baker ME; Denton MB; Pomeroy RS (1993) Imaging applications for chemical analysis utilizing charge coupled device array detectors. Trends Anal Chem 12(10): 395-403.
66. b) Warner IM; Soper StA; McGown LB (1996) Molecular fluorescence, phosphorescence and chemiluminescence spectrometry. Anal Chem 68: 73R-91R
67. a) Tietz HR (1990) Proc. XIIth Int. Congress for Electron Microscopy, Seattle,
68. b) Daberkow I; Hermann KH; Liu L; Rau WD (1991) Ultramicroscopy 38: 215.
69. c) Krivanek OL; Mooney PE (1992) Ultramicroscopy 49: 95.
70. d) de Ruijter WJ (1995) Micron 26: 247.
71. e) Tietz HR (1992) Proc 10th Eur Congr El Micr 131.
72. f) Brink J; Chiu W (1994) Applications of a slow-scan CCD camera in protein electron crystallography. J Struct Biol 113: 23-34.
73. g) Faruqui AR; Andrews HN; Raeburn C (1994) A large cooled-CCD detector for electron microscopy. Nuclear Instruments Meth Phys Res A 348: 659-663
74. Koster AJ; de Ruijter WJ (1992) Ultramicroscopy 40: 89
75. a) Dierksen K; Typke D; Hegerl R; Koster AJ; Baumeister W (1992) Ultramicroscopy 40: 71.
76. b) Koster AJ; Chen H; Sedat JW; Agard D (1992) Ultramicroscopy 46: 207
77. Nicastro D; Frangakis AS; Typke D; Baumeister W (2000) Cryoelectron tomography of neu rospora mitochondria. J Struct Biol 129
78. Wallace DC (1999) Science 283
79. a) PCR: Saiki RK; Scharf S; Faloona FA; Mullis KB; Horn CT; Erlich HA; Arnheim N (1985) Enzymatic amplification of ßglobin sequences and restriction site analysis for diagnosis of sickle-cell anemia. Science 1350-1354.
80. b) 3SR: Gebinoga M; Oehlenschläger F (1996) Comparison of self-sustained sequence replication reaction systems. Eur J Biochem 235: 256-261. Fahy E; Kwoh DY; Gingeras TR (1991) Self-sustained sequence replication (3SR), A isothermal transcription-based amplification system alternative to PCR. PCR Meth Appl 25-33. Guatelli JC; Whitfield KM; Kwoh DY; Barringer KJ; Richman DD; Gingeras TR (1990) Proc Nat. Acad Sci USA 87: 1874-1878.
81. b) 3SR: Gebinoga M; Oehlenschläger F (1996) Comparison of self-sustained sequence replication reaction systems. Eur J Biochem 235: 256-261. Fahy E; Kwoh DY; Gingeras TR (1991) Self-sustained sequence replication (3SR), A isothermal transcription-based amplification system alternative to PCR. PCR Meth Appl 25-33. Guatelli JC; Whitfield KM; Kwoh DY; Barringer KJ; Richman DD; Gingeras TR (1990) Proc Nat. Acad Sci USA 87: 1874-1878.
82. b) 3SR: Gebinoga M; Oehlenschläger F (1996) Comparison of self-sustained sequence replication reaction systems. Eur J Biochem 235: 256-261. Fahy E; Kwoh DY; Gingeras TR (1991) Self-sustained sequence replication (3SR), A isothermal transcription-based amplification system alternative to PCR. PCR Meth Appl 25-33. Guatelli JC; Whitfield KM; Kwoh DY; Barringer KJ; Richman DD; Gingeras TR (1990) Proc Nat. Acad Sci USA 87: 1874-1878.
83. c) Selex: Tuerk C; Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249: 505-510. Ellington AD; Szostak JW (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355: 850-852.
84. c) Selex: Tuerk C; Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249: 505-510. Ellington AD; Szostak JW (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355: 850-852.
85. d) phage displays: Smith (1985) Hofnung (bacterial display)
86. e) Darwinian evolution: Beaudry AA; Joyce GF (1992) Directed evolution of an RNA enzyme. Science 257: 635-641. Eigen M; Gardiner WC Jr (1984) Evolutionary molecular engineering based on RNA replication. Pure Appl Chem 56(8): 967-978
87. e) Darwinian evolution: Beaudry AA; Joyce GF (1992) Directed evolution of an RNA enzyme. Science 257: 635-641. Eigen M; Gardiner WC Jr (1984) Evolutionary molecular engineering based on RNA replication. Pure Appl Chem 56(8): 967-978
88. Merifield RB (1963) J Am Chem Soc 85: 2149
89. Mayer G; Wohlfahrt K; Schober A; Köhler JM (1999) Nanotiterplates for screening and synthesis. In: Saluz HP (ed.), Microsystem technology: a Powerful Tool for Biomolecular Studies in Biomethods Vol.10. Birkhäuser Verlag Basel, pp. 75-128
90. Eigen M (1986) 26B: 13-26, Chemica Scripta. Schuster P (1995) Biotechnol 41: 239-257
91. Eigen M (1986) 26B: 13-26, Chemica Scripta. Schuster P (1995) Biotechnol 41: 239-257
92. Woo KM et al. (1989) J Biol Chem 264: 2088. Sasaki T et al. (1984) J Biol Chem 259: 12489
93. Woo KM et al. (1989) J Biol Chem 264: 2088. Sasaki T et al. (1984) J Biol Chem 259: 12489
94. a) Balkenhohl F; von dem Bussche-Hünnefeld C; Lansky A; Zechel C (1996) Angew Chem 108: 2436.
95. b) Baldwin JJ; Henderson IA (1996) Med Res Rev 16: 391.
96. c) Jung G (1996) Combinatorial peptide and nonpeptide libraries. Verlag Chemie VCH, Weinheim
97. d) Frank R (1995) J Biotechnol 41: 259-272
98. Quinkert G; Bang H; Reichert D (1996) Helv Chim Acta 79: 1260
99. Furka A; Sebestydn F; Asgedom M; Dibö G (1991) Int J Peptide Protein Res 37: 487-93
100. a) Fitch WL; Detre G; Holmes CP (1994) J Org Chem 59: 7955.
101. b) Egner BJ; Langley GJ; Badley M (1995) J Org Chem 60: 2652
102. a) Brenner S; Lerner RA (1992) Proc Natl Acad Sci 60: 5381.
103. b) Ni ZJ; MacLean D; Holmesm CP; Murphy MM; Ruhland B; Jacobs JW; Gordon EM; Gallop MA (1996) J Med Chem 39: 1601
104. Tomandl D (1999) Selbstlernende Systeme und ihr Optimierverhalten auf Fitnesslandschaften mit Anwendungen in der Biotechnologie. Dissertation, Universität Wien,
105. a) Tomandl D; Schober A (2001) A modified general regression neural network (MGRNN) with new, efficient training algorithms as a robust 'black box'-tool for data analysis. Neural Networks 14: 1023-1034
106. Fodor SPA; Read JL; Pirrung MC; Stryer L; Lu AT; Solas, D (1991) Light directed, Spatially adressable parallel chemical synthesis
107. Groß A (2002) Automatisierte kombinatorische Chemie im miniaturisierten Maßstab zur Wirkstofffindung. Dissertation Universität Wien
108. Principles of Peptide Synthesis, Bodanszky M (1993) Springer-Verlag Berlin Heidelberg
109. Maraganore JM; Bourdon P; Jablonski J; Ramachandran KL; Fenton JW (1990), Biochemistry 29: 7095-7101
110. Schlingloff G (1999) Aufbau eines Meßplatzes mit miniaturisierter Evolutions- und Synthesemaschine. Dissertation, Universität Wien
111. Miyaura N; Suzuki A (1995) Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem Rev 95: 2457-2483
112. Zhang Y; Yunsheng H; Takashi I; Emil LT; Leslie BZ (1998) Effects of ketoconazole on the intestinal metabolism, transport and oral bioavailability of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor and a P450 3 A, Polycoprotein dual substrate, in male Sprague-Dawley rats. J Pharmacology Experimental Therapeutics 287(1): 246-252
113. Lacey ME; Subramanian R; Olson DL; Webb AG; Sweedler J (1999) Chem Rev 99: 3133
114. Tomandl D; Schober A (2003) Navigated Screening (in preparation).
115. a) Schober A; Schlingloff G; Groß A; Tomandl D; Wurziger H; Deppe H; Diefenbach B (2000) Vorrichtung für die parallele Mikrosynthese. DE 100 25 698.
116. b) Schober A; Schlingloff G; Groß A; Tomandl D; Wurziger H; Deppe H; Diefenbach B (2000) Inkubationsvorrichtung. DE 100 46 224.
117. c) Groß A; Tomandl D; Wurziger H; Deppe H; Schober A (2000) Vorrichtung zur Verhinderung von Verdunstungseffekten durch eine entweder an den Bewegungseinheiten angebrachte und mitgeführte Abdeckplatte bzw. eine statisch über den Bewegungseinheiten angebrachte Platte. DE 100 20 771
118. Gross A; Deppe H; Schober A (2003) Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer bound isocyanate. Tetrahedron Letters, 44(20): 3939-3942. Groß A (2002) Miniaturisierung von kombinatorischen Festphasensynthesen zur Automatisierung der Wirkstofffindung Dissertation Wien. Schober et al. (2003) The whole screening and synthesis process of the praeclinical drug development performed on the nanosyntest machine. (in preparation). Schober A (2003) Systemintegration, microsystems and nanotechnology: consequences for the drug discovery process. (in preparation)
119. Gross A; Deppe H; Schober A (2003) Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer bound isocyanate. Tetrahedron Letters, 44(20): 3939-3942. Groß A (2002) Miniaturisierung von kombinatorischen Festphasensynthesen zur Automatisierung der Wirkstofffindung Dissertation Wien. Schober et al. (2003) The whole screening and synthesis process of the praeclinical drug development performed on the nanosyntest machine. (in preparation). Schober A (2003) Systemintegration, microsystems and nanotechnology: consequences for the drug discovery process. (in preparation)
120. Gross A; Deppe H; Schober A (2003) Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer bound isocyanate. Tetrahedron Letters, 44(20): 3939-3942. Groß A (2002) Miniaturisierung von kombinatorischen Festphasensynthesen zur Automatisierung der Wirkstofffindung Dissertation Wien. Schober et al. (2003) The whole screening and synthesis process of the praeclinical drug development performed on the nanosyntest machine. (in preparation). Schober A (2003) Systemintegration, microsystems and nanotechnology: consequences for the drug discovery process. (in preparation)
121. Gross A; Deppe H; Schober A (2003) Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer bound isocyanate. Tetrahedron Letters, 44(20): 3939-3942. Groß A (2002) Miniaturisierung von kombinatorischen Festphasensynthesen zur Automatisierung der Wirkstofffindung Dissertation Wien. Schober et al. (2003) The whole screening and synthesis process of the praeclinical drug development performed on the nanosyntest machine. (in preparation). Schober A (2003) Systemintegration, microsystems and nanotechnology: consequences for the drug discovery process. (in preparation)
122. a) Knedlitschek et al. (1999) A tissue-like culture system using microstructures: influence of extracellular matrix material on cell adhesion and aggregation. J Biomed Eng 121: 35.
123. b) Weibezahn KF; Knedlitschek G; Bier W; Schaller Th (1994) Mechanically processed microstructures used to establish an in vitro tissue model. In: Reichl H; Heuberger A (eds), Microsystems Technologies, vde-verlag gmbh, Berlin und Offenbach, pp. 873-878
124. a) Sleytr UB; Messner P; Pum D; Sara M (1999) Crystalline bacterial cell surface layers (S-Layers) from supramolecular cell structure to biomimetics and nanotechnology. Angew Chemie Int Ed 38:1034-1054.
125. b) Pum D; Sieytr UB (1999) The application of bacterial S-layers in molecular nanotechnology. TibTech 17:8-12.
126. c) Sleytr UB; Messner P; Pum D; Sara M (eds) (1988) Crystalline bacterial cell surface layers, 193 p. Springer Verlag Berlin, Heidelberg, New York, London, Paris, Tokyo
127. Norbert S; Marufke O; Qiao F; Hohmann M; Wurziger H (1998) A Full Wafer Silicon Micro Reactor for Organic Chemistry Second International Conference on Microreaction Technology, held in New Orleans 8. -12, 3.. published 2000 in Ehrfeld W; Kessel V (eds), Wiley-VCH "Microreactors-New Technology for Modern Chemistry"