Analysis on spots - problems and (possible) solutions for combinatorial
chemistry and high throughput systems
Wednesday 17th November 1999, Sheffield, England
A one day meeting considering analysis in small areas, for instance on
combinatorial chemistry beads and on microdot arrays. Current approaches to the
problem will be reviewed and possible advances considered.
Programme:
09.30 Registration and coffee
09.55 Welcome and introduction
10.00 Single molecule detection techniques - Martin R|diger(SmithKlineBeecham)
High-throughput screening (HTS) is the major strategy for lead identification
used today in the pharmaceutical industry. Increasing numbers of biological
targets and test compounds drive the need to miniaturize assay volumes in HTS.
A number of evolving assay methods are based on detecting fluorescence of
single molecules in a tiny confocal volume element. These methods are
insensitive to miniaturisation of assay volumes, applicable to a wide range of
targets and provide an information-rich output directly from primary screening
data.
10.45 Scanning near field microspectroscopy - Francois Demangeot (Leeds Univ.)
Diffraction limits the spatial resolution of optical microspectroscopy to
approximately half the wavelength of the light used to form the image. Scanning
near-field optical microscopy (SNOM) overcomes this limit by scanning a
sub-wavelength aperture over the sample. Fluorescence and Raman images, with
simultaneous topographic maps, have been recorded with 100 nm apertures for a
variety of samples.
11.30 Surface enhanced and resonance enhanced Raman microspectroscopy - W Ewan
Smith (Univ. of Strathclyde)
Surface enhancement combined with resonance enhancement can increase Raman
scattering from a molecule by several orders of magnitude. This sensitivity and
the molecularly specific nature of the signals enables specific molecules to be
detected and identified at low concentrations and in situ on a surface or in
aqueous solution. The chemistry required to ensure reproducibility and recent
results will be described.
12.15 LUNCH and posters
13.15 FT-IR Techniques for the Study of Combinatorial Beads
- Robert Alexander (Perkin Elmer)
Combinatorial Chemistry has become an increasingly popular technique in the
armoury of the synthetic chemist particularly in the pharmaceutical industry.
A major part of this chemistry is the use of solid phase chemical reactions
(syntheses) which take place on the surface of specially designed polymer beads
or crowns (pins). It is important that the chemist has a quick and reliable
analytical technique which is capable of confirming that the correct material
has been synthesised on the bead. By using FT-IR spectroscopy on the beads the
chemist can confirm the success (or failure) of the reaction. This presentation
will compare a range of different sampling techniques (Diffuse Reflectance,
Diamond ATR, Reflectance and Transmission Microscopy, ATR-Microscopy,
Compression Cells and Raman Spectroscopy) and some general conclusions as to
the best sampling techniques will be made.
14.00 Accessing novel analytes: extending the boundaries of NMR
Russell Mortishire-Smith (Merck Sharp & Dohme)
As a structural tool, NMR has had an extraordinary impact on organic and
bioorganic chemistry. Conventionally, the organic chemist's view of NMR
spectroscopy is that it is an insensitive and time-consuming technique limited
to solution state samples. Recent developments in the field such as high
resolution MAS, flow probes and cryocooled probeheads have dramatically
extended the range of analytes on which structural information can be obtained,
and these will all be reviewed.
14.45 TEA
15.15 Miniaturised separation techniques and nanospray mass spectrometry
- Steve Lane (GlaxoWellcome)
The Efficient Analysis of Encoded Combinatorial Libraries.
Synthetic chemical libraries produced by combinatorial synthesis have rapidly
emerged as crucial tools for modern pharmaceutical lead discovery and lead
optimisation. Preparation of such libraries often rely on solid-phase
synthesis techniques coupled with the efficient "split/pool" method to assemble
a statistical sampling of all possible combinations of a set of building
blocks. Decoding the chemical structure of biologically active library members
unambiguously has represented a major analytical challenge by virtue of the
small quantities of material available from a complex library. This
presentation will describe and critically evaluate the development of relevant
modern analytical protocols.
16.00 MALDI-TOF mass spectrometry - Malcolm Clench (Sheffield Hallam Uni.)
Matrix assisted laser desorption ionisation time of flight mass spectrometry
(MALDI/TOF/MS) is an established technique for the analysis of polymers,
particularly biopolymers. There is currently a great deal of interest in its
application to the direct analysis of solid surfaces. It has been applied to
the analysis of TLC spots, the examination of drug distribution in tissue
samples and to the imaging of protein distributions. The current state of the
art for the use of MALDI in these areas will be reviewed.
16.45 Close
Venue: The Showroom, Paternoster Row, Sheffield S1 2BX
Registration: Fees (inclusive of lunch and refreshments):
Members of the RSC #50
Non members #90
Students, retired and unwaged #15
To register please contact:
Diana Hort
Analytical Division
Royal Society of Chemistry
Burlington House
Piccadilly
London W1V 0BN
Tel: 0171 437 8656
Fax: 0171 734 1227
e-mail [log in to unmask]
Meeting organised by Dr David Crowther ([log in to unmask]) on behalf of the
Analytical Division, Royal Society of Chemistry.
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