SLAS Addresses Phenotypic Screening

The annual Society for Laboratory Automation and Screening (SLAS) conference returned to San Diego, California, this year. Attendance at the conference bounced back after last year’s drop when it was held in Florida (see IBO 1/31/13), rising 53% to 5,819, nearly the same as the 2012 event (see IBO 2/15/12) (see table, page 3). SLAS 2015 will be held in Washington, DC. Over three days, the 132 conference presentations addressed seven topics: assay development and screening, automation and high-throughput technologies, bioanalytical techniques, informatics, micro/nano technologies, drug target biology and special sessions.

A special session on Monday afternoon comparing phenotypic to target-based drug discovery drew a packed house. The four speakers made a strong case for the use of phenotypic assays in drug screening as a precursor to or alongside target-based assays. David Swinney, PhD, CEO of the Institute for Rare and Neglected Diseases Drug Discovery, kicked off the session by addressing the value of phenotypic assays. It was Dr. Swinney whose 2011 article examined the fact that, of the 50 small molecular first in-class drugs with new molecular modes of action (MMOAs) approved by the FDA between 1999 and 2008, 28 were discovered using phenotypic screening approaches, despite the majority of resources being allocated to target-based drug discovery. Dr. Swinney emphasized the usefulness of empirical phenotypic assays for identifying MMOAs as well as the importance of finding clinically relevant biomarkers first and aligning phenotypic assays around them. Another speaker, Bernard Munos, founder of the InnoThink Center for Research in Biomedical Innovation, warned that the target-based approach has had an adverse effect on drug discovery by narrowing the field of inquiry and creating a cultural bias toward highly validated targets. `

MS was the topic of discussion in Tuesday morning’s automation and high-throughput technologies session. Andrew Wagner, PhD, of Bristol-Myers Squibb discussed his use of MS for in vitro assays supporting reliability assessment in early drug discovery. Although a label-free screening technology, MS’s shortcoming traditionally has been throughput. To increase throughput, Dr. Wagner’s lab employed several approaches. Using multiplex LC/MS/MS, he was able to reduce MS cycle times to 20–30 seconds per sample. Cycle time was reduced to around 10 seconds per sample using online SPE MS/MS. Employing laser desorption ionization, specifically, Nextval’s MassInsight technology, cycle times were less than a second.

In the next presentation, Hui Zhang, PhD, of Pfizer discussed his lab’s use of MS for drug discovery ADME screening. His lab’s screening of as many as 20,000–30,000 assays a week requires an automated and robust workflow. Custom software was designed for method building for compound optimization screening using high-throughput MS/MS. The lab also designed a multiplexed LC/MS system utilizing a staggered LC flow and cassette-based analysis. Commercialized by Apricot Designs as ADDA, the system consists of a dual-arm autosampler with four injection ports on each arm and is compatible with AB SCIEX MS instruments.

MS was also a topic of Monday morning’s special session on disruptive technologies. At the session, Christopher Brown, PhD, CTO of 908 Devices, previewed the company’s miniature MS system, which he said will be commercialized soon. The 3 lb handheld quadrupole ion trap system is based on a 100 g MS device. The system has a six-hour battery life and 20 second start-up time and can be operated in positive and negative modes. It features a capillary inlet and two thin-film heaters for thermal desorption. The self-contained MS module can be easily removed and replaced if contaminated. Initial applications are in the area of hazardous material identification, and the company’s spectra database currently includes up to 200 hazardous compounds.

The use of MS for high-throughput screening was also touched on during Labcyte’s press conference, indicating the new applications enabled by acoustic energy–based liquid transfer. Providing an update of three collaborations, the company discussed its work with AstraZeneca and Waters using acoustic dispensing to directly load samples into an MS for high-throughput label-free assays. The company also discussed its collaboration with the Institute of Molecular Medicine Finland for drug sensitivity and resistance testing of leukemia patients in which Labcyte’s Echo 525 liquid handler is used for screening compound combinations against patient cells. Labcyte’s collaboration with the National Cancer Institute and Stanford University is focused on developing a new method to find and validate biomarkers by detecting the volume of proteins in a sample.

Labcyte also introduced its first large-volume reagent reservoir for the Echo 525. The six-well reservoir holds 2.8 mL and dispenses 2.6 mL, allowing for zero dead volume, and features a permanently attached lid.

The exhibition featured 306 companies, compared to 310 last year. As usual, a number of new products made their debuts at the show. PerkinElmer announced two new products. The company introduced the Opera Phenix high-content imaging system, which replaces the Opera system. According to the company, it provides four-camera imaging using proprietary scanning disk confocal microscopy. Compared to the Opera, it features a larger field of view and increases the number of objectives by two to a total of six. The company also debuted the Janus chemagic nucleic acid workstation, which automates chemagic magnetic bead-based process for high-throughput DNA and RNA extraction. Standardized protocols support 10 µL to 4 mL sample volumes. The system directly integrates liquid handling into the workflow and features a six-way valve for dispensing liquids. Applications include human genetics and blood screening. The company also introduced SciStream software for importing data from microplate readers, high-content imagers and other systems into the TIBCO Spotfire Analytics and Visualization Platform.

Also for cell imaging, GE Healthcare launched its Cytell Cell Imaging System. It is positioned as a compact, affordable microscope-based imaging system that any lab can use. The four-laser system performs epifluorescent and transmitted light wide-field imaging. Designed for routine assays that would usually require three instruments (an automated microscope, cell counter and plate reader) the system can perform cell imaging; cell count, viability and concentration measurements; and fluorescence and cell morphology measurements. The product also marks the debut of GE’s BioApp products, which are application-specific modules for specific assays. The system is sold with five, and further BioApps will be made available.

Hamilton Robotics introduced several new products at the show, highlighting its focus on compact, affordable systems and standardized workstations. The new NIMBUS PCR Workstation can be used with any PCR kit. The new Microlab NIMBUS384 multichannel liquid handler features an 11- or 12-position deck, tip stacking and air dispensing multiprobe head with a pipetting range of 0.5–50 µL. It is equipped with a 384 multiprobe head that can pipet into 1535-well plates. The firm exhibited its Decapping STAR Workstation for de-capping and re-capping tubes on the Microlab STAR deck, the only system with such capabilities. Hamilton also displayed its next generation sequencing workstation, which is verified for use with Illumina and New England Biolabs kits. Previewed products included the Nimbus96 SPE system for automated positive pressure SPE.

Hamilton partnered with Coastal Genomics to automate Coastal’s Ranger Technology on the Microlab NIMBUS Select workstation. Introduced at the show, the Ranger Technology consists of agarose gel in a 12-channel cartridge for automated DNA fragment size selection. The workstation pipettes the samples into a cassette and images them during electrophoresis. Software analyzes the images, providing quality control. Fragments are then deposited in labware. Ninety samples are processed on average in two hours.

Brooks Automation introduced its next generation SampleStore and BioStore storage platforms. Designed for chemical storage, the SampleStore II has a capacity of up to 10 million tubes. The -80° C BioStore II can hold up to five million tubes. The systems combine the best technology from Brooks’ acquisitions of lab storage companies. Each system has six bays for access. Strata automated control software provides a dashboard interface for monitoring the system. The entry-level systems are each priced at under $750,000.

HiRes BioSolutions exhibited several new products at the show, including the TundraStore automated cold store. Utilizing the company’s modular approach, the TundraStore can be docked to the company’s biostores and then wheeled to other parts of lab for use with an automated workstation. The company also displayed its ACell robot, which in its tallest version has a vertical reach of up to 48 in (1240 mm), enabling flexible vertical workstation configurations. Also new is the ACell Track, a track-based version of the ACell.

Artel introduced a new software application for its MVS Multichannel Verification System for liquid handler volume-transfer verification. The LabGauge software is exclusively licensed from StackWave. The software application enables trend analysis of liquid handler performance over time. Tolerance limits can be set for different instruments, and individual well performance can be analyzed with a heat map. The cloud-based software will begin shipping at the end of the first quarter.

Dynamic Biosensors exhibited its first product, the switchSENSE biosensor, which captures a molecule on a microfluidic chip by using a DNA linker, enabling the captured molecule to be moved by voltage. The type of measurement required determines the type of voltage applied. Launched in October 2013, the technology can measure affinity and binding kinetics, molecular size, aggregation, conformational changes and thermodynamics, and works with protein, DNA or RNA. The system consists of a four-channel, 24-microelectrode chip that can be regenerated and the DRX 2400 reader with autosampler and pump.

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