LabAutomation 2006 - SLAS

TP33
Stephen Lowry
Thermo Electron Corporation
Thermo Electron Molecular Spectroscopy
Madison, Wisconsin
steve.lowry@thermo.com
LabAutomation2006
Co-Author(s)
Dave Dalrymple
Garry Ritter, Thermo Electron Corporation
High Throughput Raman Spectroscopy: Integrating the Analysis into the Laboratory
The high specificity and non destructive sampling capabilities of a Raman microscope creates an excellent platform for analyzing samples
in a microtiter plate or other array format including micro-arrays. There is a clear need for automated ways to analyze the large amounts
of data acquired from such measurements and a requirement to integrate this data with other information related to the work. In this
presentation we will describe the results of research into three areas related to the application of Raman Microspectroscopy to the analysis
and identification of materials positioned in an X,Y array. The specific example that we will discuss involves a material that can form multiple
polymorphs. Such high throughput crystallinity studies have become a critical step in the development and scale-up of new drug materials.
The three key areas that we will address are: 1) automated detection and video image analysis by Raman spectroscopy, 2) Communication
with a LIMS system and 3) The use of Supervised and Unsupervised algorithms for analyzing the spectral data to identify new polymorphs
or other unknown materials. We will describe the use of Hierarchical Cluster Analysis and Multivariate Curve Resolution to determine which
wells contain similar materials. A key challenge that we will discuss is the automatic acquisition of spectra from a well where a few small
sample particles are dispersed across a relatively large area.
TP34
David Koechlein
Deerac Fluidics
Dublin, Ireland
davidk@deerac.com
Co-Author(s)
Jean Shieh
Labcyte Inc.
Aoife Gallagher
Deerac Fluidics
Keeping DMSO Concentration Below 0.5% to Minimize its Effect in HTS Assays
Dimethyl sulfoxide (DMSO) is a commonly used solvent for compounds. DMSO accelerates protein unfolding and weakens the binding
between small molecule compounds and proteins. Consequently researchers keep DMSO concentrations as low as possible, especially
for sensitive assays. To keep the DMSO concentration at less than one percent of the final assay volume has been difficult due to the
lack of reliable nanoliter-range liquid handlers for transferring small amount of compound. Intermediate aqueous dilution steps can cause
the compound to “crash out” of solution. This issue of keeping compound dissolved in DMSO and keeping DMSO concentration low in
the assay becomes even more critical when preparing compound activity curves - the need for better nanoliter technologies is further
increased.
The Labcyte EchoTM 550 liquid handler utilizes acoustic drop ejection (ADE) to transfer 2.5-250 nL of compounds in DMSO directly from
storage plate to assay plates. Deerac Fluidics LatitudeTM bulk dispenser, which uses “spot-on” technology, can precisely deliver as low as
50 nL. Pure DMSO can be back filled in seconds to ensure the final DMSO concentration stays uniform in the assay. Here we demonstrate
the use of these two technologies in combination for keeping final DMSO concentration under 0.5% in HTS assays.
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