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Advanced liquid handling for high throughput screening

1st April 2013


Jerome Leclercq looks at the potential of a new multi-channel pipetting workstation developed for high throughput screening.

Within the past few years, life scientists have successfully sequenced the genomes of mice and men ­ and several other organisms. That research has stimulated the emergence of new disciplines like genomics, proteomics or transcriptomics.

These changes have had significant impact on drug discovery, by revealing a huge quantity of new targets with potential as drugs. The number of targets far exceeds scientists' ability to deal with them using traditional manual methods.

In response, vendors have developed high throughput screening (HTS), a process that can test large numbers of samples efficiently in very short periods of time. That ability has made HTS a key element in modern drug discovery.

Precise dispensing of micro volumes of reagents in liquid form becomes more and more important with continuing miniaturisation of the High Throughput and High Content Research process.

Applicable to all platforms, from medium and high density plates to amicro-chips', fast and repeatable liquid dispensing can often become the key to a successful experiment.

Value-added activities

Many laboratory managers start their move away from manual methods by purchasing semi-automated workstations that can pipette and deliver small volumes of reagent in microwell plates or other vessels for virtually 24 hours a day, seven days a week. By freeing lab technicians and scientists from these tasks, the workstations allow them to work on more value-added activities, such as designing experiments.

“Automation is critical to the modern drug discovery laboratory because it increases the speed and accuracy of tests, saves time, and allows the scientist to focus on science and not manual tasks,“ says Kevin Hrusovsky, president and CEO of Caliper Life Sciences. “The ability to do half a million test points in one day has opened up new strategies in exploring drugs.“

Caliper Life Sciences, formed from the combination of Zymark Corporation and Caliper Technologies, uses its advance liquid handling and microfluidic technologies to create tools that accelerate drug discovery and development, including the ScicloneALH3000, a multi-channel pipetting workstation .

The Sciclone is designed to cover the widest range of technical specification and application as required today by Scientist and buyers. Its modular configuration allows the scientists to work in 96, 384, 1536 well format within the same automated protocol, thanks to automatically exchangeable pipetting tools.

Furthermore, the users are able to choose between fixed cannulas or disposable tips or both, compromising between cost of assay and sample integrity. Among the flexibility criteria, scientists expect the workstation to cover the widest volume range with the highest precision and accuracy specification.

The Sciclone has aswappable' dedicated pipetting heads which allow the user to select between the 100nl range up to the 200µl range.

The new microplate formats have the advantage of reducing the volumes of samples needed for individual wells to microlitre and submicrolitres or even to nanolitre amounts in the microarrays world. That reduces the cost of reagents. But it comes with a penalty: the physics of moving and measuring small quantities of fluids differs considerably from that of larger, more conventional volumes.

Again, automation comes to the rescue. New liquid handling technology is now available to allow the precise measurement and dispensing of liquid quantities in the 10 nanolitre range.

The inL 10 Sciclone system is capable of measuring liquid volumes in the single nanolitre range. This not only permits scientists to use very small quantities in their testing, but also allows fewer repeat tests because the equipment confirms that the right quantity has been dispensed. Drug discovery researchers are enabled to make better decision by providing high quality data that eliminate false positives and false negatives.

Demand for the workstations has expanded beyond HTS laboratories in the big pharma organisation. Instrument vendors are going to the smaller market that means user friendly systems and turnkey application.

Covering a wide range of application, scientists from both Caliper and consumable ad reagent kit manufacturers are partnering to develop pre-optimised protocols that can be successfully automated on the Sciclone.

The Sciclone now can do everything in molecular biology (PCR setup, DNA extraction, SNP), in proteomics, in Drug screening (Cell based assay, ELISA's, Profiling, secondary screening), in ADMETox (inhibition, Caco2) and in many more scientific fields.

Laboratory automation tools range from simple semi-automated liquid handling devices to fully integrated automated systems that consist of multiple robot arms, pipetting stations, incubators, plate washers, and detectors. This is critical that validated liquid handling protocols can be transferred from standalone workstation to fully integrated robotic systems.

Modularity and expandability are now key decision criteria to optimise method transfer from assay development lab to HTS lab for example.

Therefore, the Sciclone is the core module of larger automated systems. Fully compatible with Caliper's integration software, it will be served by storage devices and robotic arms like Twister II, the most widely used universal microplate handler on the market.

Pharmaceutical and biotech companies have recognised the need for automated solution to perform more and more sophisticated assays. But the pressure on high quality data, time to market and R&D cost reduction force the lab scientist to be more and more sensible to high standards of technical specification as well as secured return on investment.

Jerome Leclercq is with Caliper Life Sciences, Paris, France. www.caliperls.com





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