Caliper chief considers state-of-play in lab automation

Related tags Drug discovery High-throughput screening

Just ahead of the Lab Automation Europe and International Biotech
conferences in London this week, spoke with
Kevin Hrusovsky, the chief executive of Caliper Technologies, to
get his take on the current state of play in how technologies are
transforming the business of drug discovery.

Hrusovsky was head of liquid-handling company Zymark before the company merged with Caliper earlier this year, and has been involved in developing laboratory automation systems for the pharmaceutical and biotechnology industries for many years. He believes there are several issues behind the alarming decline in R&D productivity that is causing such consternation in the boardrooms of drug manufacturers.

One is simply that the cost of doing experiments has become very high as scientists push back the frontiers of scientific knowledge into uncharted territory, tackling new and unvalidated drug targets. Meanwhile, the industry is only just starting to see efforts to integrate the numerous technologies such as high-throughput screening (HTS) that have been developed over the last few years into more pragmatic, rational system for discovery.

Another major issue is the attrition rate of compounds coming through development, particularly as companies are looking more and more at new drug targets about which little is known.

"70 per cent of the cost of drug development can be attributed to drug failures,​ according to Hrusovsky, he added that often this is because the tools for screening are not effective enough in identifying the best compounds, either on safety or efficacy grounds.

Companies are now exploring ways to get information sooner about the effects compounds have in the body, by marrying technologies such as genomics and proteomics with screening in the earliest stages of drug discovery, he noted.

This should provide a much clearer picture of the profile of a compound and reduce the risk that unexpected side effects will emerge to kill the project later, or indeed cause the deaths of patients; drug side effects are the second highest cause of death in the US.

Another issue that is causing concern among researchers is that an increased emphasis on automation may have an inhibiting effect on creativity and innovation. In the early days, there was an idea that the answer to the industry's R&D productivity would be to throw more compounds into the HTS process and hope to get more drugs out at the other end.

This proved to be far from the case, noted Hrusovsky, but latterly there has been a switch in emphasis, with scientists working in HTS moving to what he described as a 'strategic screening' approach, seeking ways to expand the data that can be achieved using these technologies.


In terms of Caliper's own core technologies, Hrusovsky noted that liquid handling and automation has already had a profound effect on the sector, particularly with regard to making it possible to push the boundaries of HTS. However microfluidics - a liquid handling technology that uses volumes at the nanolitre scale - is still in the early stages of adoption.

Over the last few years, the microfluidic or lab-on-a-chip sector has been plagued by problems of insufficient throughput, unreliable data and mundane problems such as plugging of the tiny channels used in the products. However, most of these issues have now been overcome, and Hrusovsky believes that customers are now seeing a significant increase in data quality that is stimulating interest in the technology.

For example, Caliper's systems can be used to set up kinase assays with the ability to detect just 20 per cent inhibition, compared to 50-60 per cent with other approaches. This not only expands the number of potential 'hits' in a screen, but also could pick up safety issues, such as activity against another kinase, that would not appear using microtitre technologies.

Interestingly, one of the original claims for the technology was that it would cut down on reagent and other consumable costs. This has not in fact been the case, said Hrusovsky, because 70 per cent of users tend to use the chips as detectors, relying on traditional microtitre plates to handle the delivery of compounds and reagents.

"The real power of microfluidics comes when researchers do both sample preparation and detection on the chip,"​ said Hrusovsky, but only 30 per cent of Caliper's customers are using this approach.

The promise of microfluidics is perhaps best revealed by Caliper's customers. At the ISLAR meeting earlier this year, one client presented a study showing that it had been able to run a protein kinase screen using Caliper's microfluidics products at a cost of around $70,000. Using conventional microtitre plates would have swelled this to around $7 million, and the work would simply not have been carried out.

"We are on the cusp of a whole new era of testing competence,"​ Hrusovsky told, pointing to the broad utility of its platform in testing kinases, phosphatases and proteases, as well as conducting calcium flux and ion channel cell-based assays.

Next year, Caliper is planning to launch a new microfluidics platform that, it believes, will bring the company closer to its goal of achieving mass adoption of microfluidics.

The new system, provisionally called the Caliper 300, is effectively an update of the Caliper 250. Around 40 of the latter systems have been sold to customers for screening using enzymatic and cell-based assays.

The 300 will be one-third of the size and will be priced at a level that will make it more accessible to smaller companies, said Hrusovsky. However, its main advantage will be a hike in throughput, achieved by allowing 12 experiments to be run in parallel on the chip. At present, all but the newest 250 systems can only manage four. In addition, the 300 will be able to run adherent cells, such as CHO cells, he noted, expanding its capabilities in cell-based calcium flux assays.

Related topics Preclinical Research Ingredients

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