Editor’s Page SLAS2014: Focus on Throughput and Data Quality by Robert L. Stevenson T
he 3rd annual Conference and Exhibition of the Society for Laboratory Automa- tion and Screening, SLAS2014, was held
January 18–22 in the east end of the San Di- ego Convention Center. In lab automation and screening, improved data quality and higher throughput are the two main drivers. Cost re- duction is a distant third. Reports describing mass spectrometry for qualitative and quan- titative analysis dominated the lectures in the Automation Track. Most of the applications fo- cus on life science, especially pharmaceuticals.
Automation lectures The scientific lecture program consisted of six
parallel tracks: Automation, Informatics, Assay Development, Bioanalytical, Diagnostics and Biomarkers, and Nanotechnologies. Space does not allow coverage of the hundreds of new as- says that were described.
Automated library synthesis The drug discovery and development cycle
begins with generating compound libraries, the more the better. Dr. Alberto Bresciani of IRBM Science Park (Pomezia, Italy) explained automated library synthesis in dimethylsulf- oxide (DMSO). Suitable reactions usually give better than 70% purity, which is sufficient for testing without a purification step. Plus the product is in DMSO, which fits directly into many assay protocols.
Dr. David Parry of Cyclofluidic Ltd. (Welwyn, U.K.) extended the process further to a micro- fluidic system that increases throughput even more, giving structure activity relationships (SARs) in minutes. Integrating the synthesis with assay on a single platform is the key advance.
Detection is with MS and liquid chromatogra- phy/evaporative light scattering detection (LC/ ELSD). Reactions that do not meet acceptance criteria are excluded from the SAR.
I was particularly intrigued with the lecture from Victor Sans of the University of Glasgow (Scotland) describing fabrication of chemical synthesis workflows using 3-D printed reaction- ware. Reactionware combines chemicals with reactors using a logical workflow. Polypropylene is the preferred material. One example connect- ed reactors for hydrogenation with Pd/carbon and Lewis acid catalysis reactors.
Moving downstream to formulation and pro- cess development, Dr. Eva Ping of Chemspeed Technologies (New Brunswick, NJ) de- scribed the firm’s automated workstations. Chemspeed offers automated unit operations, from synthesis reactors and incubators to prod- uct packaging. Integrated software facilitates scaleup as well as control and reporting.
Lead evaluation Surface plasmon resonance (SPR) instruments
provide convenient measures of the kon koff of binding reactions. However, these re-
and
quire making runs at 6–10 concentrations to generate the binding curve. This is slow by contemporary standards. Anthony Giannetti of Genentech (South San Francisco, CA) used continuous gradients in a microfluidic device to study binding while the concentration changes by several logs. The new method is much faster, uses much less reagent, and is more automated.
Binding of proteins with ligands produces shifts in the nuclear magnetic resonance (NMR) spec- trum for the atoms involved, particularly 2-D
AMERICAN LABORATORY • 4 • JUNE/JULY 2014
NMR of 1H and 15N. Dr. Maurizio Pellecchia of Sanford-Burnham Research Institute (San Diego, CA) showed that NMR is useful in screen- ing large libraries (~200,000 compounds). Resonance shifts can be mapped directly to the drug-binding site, which aids in demonstrating the mechanism of action (MoA).
MS combines qualitative and quantitative analysis with high
throughput Seven lectures and numerous posters de- scribed label-free technology for screening, usually with throughput of several assays per minute. For example, Dr. Karen Maegley of Pfizer Oncology (Groton, CT) used multiple reaction monitoring in a quadrupole MS to measure the activity of isoprenal cysteine carboxylmethyltransferase. The reaction prod- ucts are S-adenosyl homocysteine and methyl cysteine. The platform has been used to char- acterize Pfizer’s epigenetic library.
Dr. Andrew Wagner of Bristol-Myers Squibb (New York, NY) compared several approaches to high-throughput screening of libraries. One, involving high-throughput solid-phase extrac- tion (SPE) with the ADDA system from Apricot Design (Covina, CA), gave modest purification with an analysis time of about 5 sec. However, if the SPE step is not needed, he showed that laser desorption ionization (LDI) of a porous silicon chip provides throughput faster than 1 sample/ sec. To avoid a keyhole of plate preparation, Pfizer uses acoustic nanodispensing technol- ogy to print an aliquot of the sample directly to the plate, which then goes to the LDI-TOF/MS (time-of-flight mass spectrometer).
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