L25 Hurray for the chemical microarray—Massive parallel analysis of proteases, kinases and cells...
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european journal of pharmaceutical sciences 34S ( 2 0 0 8 ) S7–S24 S17 2006). Another valuable advantage that co-crystal synthesis may offer for the pharmaceutical industry is an opportunity to address intellectual property (IP) issues by extending the life cycles of old APIs. The recent developments, challenges and drawbacks in the area of pharmaceutical co-crystallization will be presented. references Almarsson, ¨ O., et al., 2004. Chem. Commun., 1889. Blagden, N., et al., 2007. Adv. Drug Deliv. Rev. 59, 617. Vishweshwar, P., et al., 2006. J. Pharm. Sci. 95, 499. doi:10.1016/j.ejps.2008.02.039 NANO- AND MICROTECHNOLOGY IN PHARMACY L25 Hurray for the chemical microarray—Massive parallel analy- sis of proteases, kinases and cells on glass slides Mark Bradley School of Chemistry, University of Edinburgh, UK A 10,000 member peptide nucleic acid (PNA)-encoded pep- tide library was prepared, treated with a number of kinases and decoded using a DNA microarray and a fluorescently labeled anti-phosphotyrosine antibody. A dual-color approach ensured internal referencing for each and every member of the library and the generation of robust data sets. Analysis identified peptides that were strongly phosphorylated in full agreement with known specificities. BLAST analysis identi- fied both known cellular substrates as well as new potential target proteins. The kinases Her2 was demonstrated to have a marked preference for d-proline offering a unique means of targeting and inhibiting this kinase. The power of this approach in the analysis of proteases and the discovery of cell specific ligands will also be demonstrated. Left: Schematic of the application of PNA encoded pep- tide libraries as used in kinase profiling. Right: Image of the 22,575 member custom DNA microarray (using the kinase Abl), obtained using a Cy3 filter. Every fluorescent spot (the red spots in white circles) represent a “hit”, a unique peptide that has been recognized and phosphorylated by Abl. doi:10.1016/j.ejps.2008.02.040 L26 Materials and technologies for analytical microsystems Sami Franssila Department of Micro and Nanosciences, Helsinki University of Tech- nology, Finland Microdevices for chemistry are much more varied than the electronic microdevices. This variety places a number of lim- itations and challenges for device fabrication. Silicon properties known in detail; process technologies well developed; excellent surface finish and dimensional control; IR transparency and UV–vis absorption. Glass a mix of related materials, with a variety of properties; transparency, surface chemistry, thermal insulation good; in a silicon lab glass (sodium) poses a contamination prob- lem; limited choice of processing technologies. Polymers almost unlimited materials selection; thermal and chemical stability does not match silicon and glass; autofluorescence, contamination, porosity, permeability; mix of microfabrication and scaled down traditional fabrica- tion. Fluidic devices consist of channels, mixers, reservoirs, valves, nozzles and other individual components. Size scale tends from millimeters to micrometers down to nanometers. Some of these patterns are critical, for example, pass size of a filter, but many others are non-critical, like fluidic reservoirs. This can lead to overly costly fabrication if size and criticality are not given proper consideration. On the other hand, rely- ing on simple fabrication like PDMS casting will limit options available. Fabrication complexity stems partly from three- dimensional nature of most fluidic devices. Deep and high aspect ratio structures need to be made (by lithography, etching, hot embossing) and these structures need to be bonded to form liquid tight systems. Bonding of silicon and glass is standard, as long as one accepts the fairly high bonding temperatures (300–1000 ◦ C). Bonding polymers is much less developed technology, and consists of materials specific techniques which include adhesive bonding, solvent, thermal, ultrasonic, microwave, laser, plasma activated, etc., bonding. doi:10.1016/j.ejps.2008.02.041
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Transcript of L25 Hurray for the chemical microarray—Massive parallel analysis of proteases, kinases and cells...
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006). Another valuable advantage that co-crystal synthesisay offer for the pharmaceutical industry is an opportunity
o address intellectual property (IP) issues by extending the lifeycles of old APIs. The recent developments, challenges andrawbacks in the area of pharmaceutical co-crystallizationill be presented.
e f e r e n c e s
lmarsson, O., et al., 2004. Chem. Commun., 1889.lagden, N., et al., 2007. Adv. Drug Deliv. Rev. 59, 617.ishweshwar, P., et al., 2006. J. Pharm. Sci. 95, 499.
oi:10.1016/j.ejps.2008.02.039
ANO- AND MICROTECHNOLOGY IN PHARMACY
25
urray for the chemical microarray—Massive parallel analy-is of proteases, kinases and cells on glass slides
ark Bradley
School of Chemistry, University of Edinburgh, UK
A 10,000 member peptide nucleic acid (PNA)-encoded pep-ide library was prepared, treated with a number of kinasesnd decoded using a DNA microarray and a fluorescentlyabeled anti-phosphotyrosine antibody. A dual-color approachnsured internal referencing for each and every member ofhe library and the generation of robust data sets. Analysisdentified peptides that were strongly phosphorylated in fullgreement with known specificities. BLAST analysis identi-ed both known cellular substrates as well as new potentialarget proteins. The kinases Her2 was demonstrated to have
marked preference for d-proline offering a unique meansf targeting and inhibiting this kinase. The power of thispproach in the analysis of proteases and the discovery of cellpecific ligands will also be demonstrated.
Left: Schematic of the application of PNA encoded pep-ide libraries as used in kinase profiling. Right: Image of the2,575 member custom DNA microarray (using the kinase Abl),btained using a Cy3 filter. Every fluorescent spot (the red
pots in white circles) represent a “hit”, a unique peptide thatas been recognized and phosphorylated by Abl.oi:10.1016/j.ejps.2008.02.040
l s c i e n c e s 3 4 S ( 2 0 0 8 ) S7–S24 S17
L26
Materials and technologies for analytical microsystems
Sami Franssila
Department of Micro and Nanosciences, Helsinki University of Tech-nology, Finland
Microdevices for chemistry are much more varied than theelectronic microdevices. This variety places a number of lim-itations and challenges for device fabrication.
Silicon
properties known in detail;process technologies well developed;excellent surface finish and dimensional control;IR transparency and UV–vis absorption.
Glass
a mix of related materials, with a variety of properties;transparency, surface chemistry, thermal insulation good;in a silicon lab glass (sodium) poses a contamination prob-lem;limited choice of processing technologies.
Polymers
almost unlimited materials selection;thermal and chemical stability does not match silicon andglass;autofluorescence, contamination, porosity, permeability;mix of microfabrication and scaled down traditional fabrica-tion.
Fluidic devices consist of channels, mixers, reservoirs,valves, nozzles and other individual components. Size scaletends from millimeters to micrometers down to nanometers.Some of these patterns are critical, for example, pass size of afilter, but many others are non-critical, like fluidic reservoirs.This can lead to overly costly fabrication if size and criticalityare not given proper consideration. On the other hand, rely-ing on simple fabrication like PDMS casting will limit optionsavailable.
Fabrication complexity stems partly from three-dimensional nature of most fluidic devices. Deep andhigh aspect ratio structures need to be made (by lithography,etching, hot embossing) and these structures need to bebonded to form liquid tight systems. Bonding of silicon andglass is standard, as long as one accepts the fairly highbonding temperatures (300–1000 ◦C). Bonding polymers ismuch less developed technology, and consists of materialsspecific techniques which include adhesive bonding, solvent,
thermal, ultrasonic, microwave, laser, plasma activated, etc.,bonding.doi:10.1016/j.ejps.2008.02.041
