A Special Report by the Editors of Laboratory Equipment
Micrograph of H1N1 virus.
Photo courtesy of Cynthia Goldsmith, Centers for Disease Control and Prevention.
For this Special Report, the editors of Laboratory Equipment surveyed and interviewed researchers working in life science applications, along with developers of the instrumentation and equipment these researchers use in their labs.
Separate surveys were sent to each group, who often responded similarly. Regarding the next five years, both agreed that the biofuel, cell biology, genomic, and personalized medicine applications would see the most technological growth. Scientists felt that agricultural, animal science and environmental applications would see significant growth as well; most instrument developers, however, did not.
In the instrumentation arena, both agreed that ease of use, flexibility, speed and sample throughput would see the largest performance changes. Although still desired and demanded, improvements in accuracy, resolution and sustainability will take a backseat to those improvements that affect lab productivity and overall costs.
Improved ease of use stood out among all other areas as researchers and lab managers attempt to deal simultaneously with their organizations’ demands for increased throughput, shortages of skilled staff, and the increasing complexity of each new generation of analytical techniques.
“We’re focusing more closely on application solutions,” says Jason March, director of marketing at Hamilton Co. “We will create products that streamline the research process, reducing labor, reagents and waste.”
Deepak Sharma, senior product manager at Photometrics and QImaging agrees: “We’ll move significantly into solving customer issues rather than just focusing on technological challenges.”
Over the next five years, the life science arena “will see an increasing emphasis on products that characterize the ‘new particle’ in a variety of industries,” says E. Neil Lewis, technical director at Malvern Instruments. “These particles include proteins, viruses, lipid vesicles, nanoparticles and more. As a result, our products will have to seamlessly support a user base that is increasingly diverse. This will drive the need for sophisticated, embedded solutions/assays within our product offerings, and these solutions will need to be simple to deploy and validate.”
Easier, but more complex
“If the pace of innovation continues like it has over the past five years, we can expect to see significant improvements in [instrument accuracy, ease of use, sustainability, flexibility, resolution, speed and throughput] over the next five years,” says Jeff Mazzeo, biopharmaceutical business director at Waters Corp.
Instrumentation characteristics that were considered high-end just a few years ago are now becoming common tools used by life science researchers. Technologies like TOF, UHPLC, triple-quadrupole mass spectrometers and detectors with improved quantum efficiencies are now routinely available from various instrumentation suppliers.
Triple quadrupole LC-MS systems now have femtogram-level detection limits with six times better sensitivity than the instruments they replace. Hundreds of compounds can be analyzed per instrument injection at rates of 150/sec or higher. One 96-well microplate, for example, can be analyzed on Agilent’s 6400 Series triple quads in just 10 minutes.
These types of instruments allow scientists to do more tests with the same amount of materials but faster.
“Our UPLC instrument and chemistry technology combined with our Q-TOF mass spectrometers and informatics solutions will have a great impact on the life sciences, especially in the high-growth biopharmaceuticals,” says Mazzeo. “Methods for protein identification and quantitation will allow better safety assessment than current immunoassay methods.”
Understanding the higher order structure of biopharmaceuticals is critical to safety and efficacy. Current methods do not provide the detail or throughput required by the industry.
“New life science applications will also be developed for NMR, Raman and mass spectrometry,” says Haydar Kustu, Bruker’s corporate marketing manager. “These products will rapidly gain popularity over existing time-consuming and less accurate methods.”
These improvements in analytical instrumentation do not take away the inherent complexities of characterizing and analyzing biological materials. Biological assays are primarily based on statistical studies, which are built on samples that are often variable from one sample to the next, even when sourced from the same patient. Instruments that work with extremely small samples allow multiple tests to be run on a single sample, thereby improving and validating the statistical results.
Samples can also be taken from a single cell, minimizing the variability issues even further. “We can amplify the DNA from a single cell and get tens of thousands of exact copies,” says John Langmore, VP of commercial development at Rubicon Genomics.
Although full representation of the genome in the Rubicon process is not achieved, 70% to 90% of the genome is highly represented in a reproducible way. This allows studies of heterogeneity within populations of cancer and stem cells.
“Given the new techniques for culturing primary and stem cells, these rarely used cell lines will become the basis for all cell-based research and high-throughput screening over the next five years,” says Hamilton’s Jason March. “The results that come from these high-content screens will further quicken the pace of research.”
Project funding is the biggest life science issue faced by scientists, reported more than half of the Laboratory Equipment survey respondents. They also chose regulatory approvals (48% of respondents), skilled personnel (38%), clinical tests (36%) and long development cycles (34%) as issues.
These responses could be particularly troublesome in that 51% of the same researchers indicated that their 2010 life science research budgets would be the same as this year. About a quarter (27%) said their budgets would increase, and 22% said they would see a decrease in life science funding support.
The 2009 American Recovery and Reinvestment Act (ARRA) funneled a relatively big portion of the $18 billion allocated for R&D into a number of mostly academic and government labs. As a result, a number of life science programs will be enhanced this year and next. The ARRA funding, however, is mostly gone by mid-2010 with no indication from Washington that any of these one-time funds would be repeated.
The economy, the transition of traditional drug development programs at big pharma to an integrated biopharmaceutical model, and the decline of new drug products in the pharmaceutical pipeline are contributing to the basically flat life science funding growth going into 2010.
This is doubly troublesome—the enhanced life science instrumentation and equipment discussed earlier have significant price tags attached. These instruments and technologies are critical to maintaining the competitiveness of U.S. life science organizations, especially in relation to their competitive counterparts in Asia, who continue to have double-digit R&D funding increases throughout the recession and its aftermath.
Instrument developers and scientists alike expect the most technological growth in imaging systems over the next five years.
“Disruptive imaging technologies will be introduced that will inject imaging with new technical possibilities,” says Photometrics’ Deepak Sharma. These systems will be enhanced simultaneously with higher resolution, faster speeds and increased sensitivity due to CMOS (complementary metal oxide semiconductor) technologies, says Sharma.
These developments have been evolving over the past several years with technologies like laser tweezers, 3-D resolution and bi-directional wavelength capabilities. Along with CMOS, the decreasing cost of computer memory, cross platform functionality and improved software will enable these improvements, says Sharma. “We’re also likely to see the development of integrated imaging modalities over the next five years.”
“Improvements in the ease of use and automation of imaging systems will also enable these technologies to be used outside of the elite research labs and into organizations focused on solving basic healthcare issues,” says Jens Greiser, product marketing manager in life sciences for FEI.
“Life science technologies will unite to form hybrid imaging techniques (i.e. combining NMR, X-ray, light microscopy and electron microscopy) to allow the visualization and modeling of time-resolved macromolecular processes, which provide direct measurement of the underlying workings of the cell,” says Greiser.
A sticking point in these developments is the “complete lack of standardization in imaging applications,” says Sharma. Standards exist in a lot of areas, like electronics and materials, but imaging applications are very arbitrary. It’s even difficult for two labs to compare results with the same modalities, let alone with a hybridization of different modalities.
Astronomers utilizing a system involving photon numbers have made some efforts in this area, but transitioning this to life science applications is still a long way off.
Level playing field
The U.S. has traditionally been the leader in life science, from development of pharmaceuticals and genetically modified crops to medical technologies and biotech. The global leaders in each of these areas have their headquarters and central research labs in the U.S.
That leadership may be at risk over the next five years, as U.S. life science companies outsource some of the research to other countries, form collaborations with foreign companies, and establish global research centers. Recent studies by the Organization of Economic Cooperation and Development (OECD) and UC Berkeley have found that international mobility of highly skilled workers is increasing in scale and complexity and economies participate in R&D and innovation activities.
One third of the respondents to Laboratory Equipment’s reader survey indicated that they planned to increase their life science outsourcing work in 2010 to Asian and European organizations. The Berkeley report recommends the creation of strategies to ensure that this trend does not dramatically affect U.S. competitiveness.