Caliper Life Sciences has built on its microfluidics technologies to become a commercially focused life sciences company. Mark Whitfield reports

Caliper Life Sciences has built on its microfluidics technologies to become a commercially focused life sciences company. Mark Whitfield reports

Caliper Life Sciences has been through a period of great change over the past two years. It has made a major acquisition, restructured its senior management, changed its name and refocused its business.

The company, based in Massachusetts, US, has developed leading microfluidic, liquid handling and automation technologies to accelerate drug discovery and enhance disease diagnosis.

Originally headquartered in Mountain View, California, Caliper Technologies (as it was then called) was formed between 1995 and 1997 when its founders began to license technologies from universities across the US to develop an expertise in microfluidics.

Caliper has now grown into a leading liquids handling, microfluidics and automation company, employing approximately 450 people worldwide and providing a range of integrated macro- and microfluidics laboratory solutions for the life sciences industry.

Since its formation, Caliper has built on the patented microfluidics technologies it licensed and, over the past 18 months, has evolved from a primarily technology driven organisation into a commercially focused life sciences company which is expected to turn over $80-85m (?44-46m) in 2004.

According to Kevin Hrusovsky, chief executive officer of Caliper Life Sciences, ’over the past five years there has been an investment of $120m in the company, which has been used to develop our microfluidics technology and our patent estate, which has been ranked by MIT Technology Review at number two in the entire biotech sector. We are now focused on realising the rewards of that investment by making these technologies commercially viable.’

Caliper has a long-standing relationship with Agilent Technologies which began in May 1998. In September 1999, Agilent introduced the 2100 Bioanalyser system, which is based on Caliper’s patented technology and uses Caliper’s LabChip devices. The two companies went on to expand the offerings from their collaboration.

Although Caliper and Agilent continue a fruitful partnership, the exclusivity terms of that relationship ended in May 2003. Two months later Caliper entered into an agreement with Bio-Rad, a life science research product and clinical diagnostics manufacturer and distributor based in Hercules, California. The agreement has led to the development of products based on Caliper’s LabChip technology, which complements Bio-Rad’s instrument and technology expertise and market presence.

Caliper Technologies realised that its expertise in microfluidics offered excellent commercial opportunities. However, its own efforts to commercially develop its core technologies were not achieving results quickly enough. So in July 2003, Caliper acquired Zymark, a Massachusetts-based manufacturer of laboratory automation, robotics, and workstation-based products for use in the research and analytical laboratory environment.

At the time, Zymark had around three times the revenue of Caliper and its acquisition has led to many changes. Caliper’s innovative technologies and microfluidics research and development expertise were immediately complemented by a management team skilled in commercialising specialist automation technologies. Additionally, Zymark had established sales and distribution channels and the ability to engineer and produce instruments at relatively low cost.

Caliper Technologies moved its headquarters from California to Zymark’s existing corporate centre in Hopkinton, Massachusetts. Then in January 2004 Caliper Technologies changed its name to Caliper Life Sciences.

’We needed to signal to our customers that we were now focused on serving the life sciences industry as a whole, rather than selling a particular technology,’ says Hrusovsky. ’A different approach was needed. Zymark had been building a laboratory infrastructure in drug discovery and development, and genomics and proteomics, for many years - so coming together made a great deal of sense.

’One area of focus is the macro/micro interface. Caliper’s technology had become an island, but now we see LabChip technology meeting with traditional technology, such as liquid handling, in a way which makes it easier to commercialise.’

Since the Zymark acquisition, Caliper Life Sciences has become more successful in terms of the acceptance of its technology and has gained commercially. Its microfluidics technology and services are now accepted by many major pharmaceuticals companies including, Novartis, Merck, Johnson & Johnson, and Aventis to name but a few. The list is extensive.

In terms of the company’s financial performance, Hrusovsky says: ’We have met all our targets in each of the past four quarters. In the past 20 months Caliper Life Sciences has seen its enterprise value increase by approximately $200m.’

The commercial power provided by the Zymark acquisition has proven to be the most important change over the past few years. The instrument packaging, applications expansion, and involvement of key industry scientists in developing the technology have contributed to the company’s recent success. As Hrusovsky puts it: ’The whiz-bang of Caliper’s technology now has much greater commercial relevance.’

Mark Roskey, Caliper Life Sciences’ vice president for worldwide marketing, says: ’The potential power of combining macro and micro technologies has charged up the market. Combined, they provide a new, valuable solution for the laboratory with superior data and results. Faster, more precise and dependable results are achievable.’


Mark Whitfield is a freelance science writer based in Kent

Technology focus

Caliper Life Science’s LabChip technology allows researchers to precisely control the flow of minute amounts of fluids through a chip that looks similar to a microchip. Only small amounts of sample or reagent are required for a test. Reactions are processed more quickly and many functions, for example mixing or pipetting, can be automated on the chip. The result is more accurate data, achieved more quickly and at lower cost.

The chips are manufactured using microfabrication to produce intricate designs of interconnected channels that are extremely small and precise. Each chip is designed to support the series of steps in a researcher’s experiment. Once the chip is designed, photolithography is used to replicate the pattern as channels on a sheet of glass or quartz. A typical channel is 50?m wide and 10?m deep. Another plate, containing the holes through which fluids will be introduced to the chip, is bonded on top. After bonding, the sheets are cut into individual chips.

In certain applications, sippers introduce minute quantities of liquid into the chip for the reaction. Sipper chips allow automated sampling from microtitre plates, making microfluidics technology more versatile and widely applicable.

Caliper is focusing on three areas through both its direct and partnership business channels:

. Molecular diagnostics - in Caliper’s chief executive officer Kevin Hrusovsky’s assessment, this segment offers the greatest potential, but the use of microfluidic technology here is still in its infancy.

Caliper has developed expertise in performing automated high throughput polymerase chain reaction in a microfluidic sipper chip. The system integrates reaction assembly, thermal cycling and fluorescence detection on one chip, allowing testing on a nanolitre scale to be automated. The chip used employs a ’sip-and-split’ design and in its present configuration has eight channels in which eight different loci can be amplified at one time for each sample. Caliper has also configured the system to continuously amplify and detect single molecules of DNA.

. In drug screening and profiling, enzymatic assays and cell-based assays are run on the LabChip 3000 drug discovery system, which was launched in February 2004 as a completely re-engineered version of an early Caliper high throughput screening system. Major target classes include kinases, phosphatases, proteases, and G protein-coupled receptors.

The enzymatic assays are based on mobility shift electrophoresis in which product and substrate peaks are separated and detected independently. Cell-based calcium flux assays measure levels of intracellular calcium in individual cells. The miniaturisation of the process provides significant reduction in cell management, as around 100 times fewer cells are required for each screen.

. In separations, products available include Agilent’s Bioanalyzer 2100, Bio-Rad’s Experion System, and Caliper’s LabChip 90 automated electrophoresis system. The LabChip 90 is designed for higher throughput research and production laboratories analysing DNA and protein samples. It uses Caliper’s microfluidic ’sipper chips’ to sample directly from 96- or 384-well plates.