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Nanoflow Enhances LC Devices

By Robert M. Frederickson

Oct 17, 2005 | Recent product withdrawals requested by the FDA and ballooning R&D spending despite disappointing drug pipelines have placed tremendous pressure on pharmaceutical manufacturers. To respond to safety issues, drug developers now require a greater number of tests earlier in the development process that can predict drug-like characteristics of lead compounds and that can identify appropriate pharmacokinetic and toxicity profiles.

The genomic era of drug discovery ushered in a style of research characterized by high-throughput science — screen thousands of drug targets against a vast array of chemical compounds, with the hopes that eventually a blockbuster would fall out — and the faster the better. However, the blockbuster model is being complemented by an approach designed towards identifying niche drugs for smaller patient populations.

In response to these changes, drug screening labs are placing higher value on the quality of experimental data and the insights that such data can provide and are focusing less on simply increasing the throughput of screening activities. The mantra has moved from more information to better information. Drug screening reagent and platform providers hope to address this need with products that save users time and therefore money by providing more usable and reliable information with less effort.

A case in point can be found with Eksigent Technologies. Eksigent, founded in 2000, provides microscale liquid pumping and flow control devices for liquid chromatography (LC) applications. They have targeted the LC market, as HPLC is the most widely used analytical instrument in the biomedical sciences, used by all pharmaceutical and biotechnology companies in both drug discovery and analysis of drug metabolism in clinical trials. HPLC and LC are often coupled with mass spectrometric analysis, which can identify compounds from drug metabolites to large proteins and complexes.

Eksigent’s Microfluidic Flow Control pump technology eliminates the flow splitters found in traditional HPLC instruments. The aim is to provide researchers the ability to immediately adjust flow rates for more accurate, consistent, and precise analyses. The technology is based on microfabricated systems created by lithographic techniques and uses continuous feedback to an electronically controlled pressure source to maintain precise nanoscale flow rates as low as 20 nL/min without flow splitting. New drivers can be integrated with Thermo Electron’s Xcalibur and Applied Biosystems/MDS Sciex’s Analyst 1.4.1 mass spectrometer platforms. Users can operate the ExpressLC-100 and the mass spectrometer as one integrated system.

Micro-Tech Scientific launched a competitive product in 2004 called the X’TremeSimple NanoHPLC system that offers precise low-volume flow control without the use of splitters. The system, compatible with the Xcalibur and Analyst platforms, can be used for nano-LC-MS, capillary-LC-MS, proteomics drug discovery, protein drug quality control, and automated microtiter plate sample preparation for MALDI-MS. Micro-Tech also offers the Ultra-Plus, a microflow product comparable to the Eksigent ExpressLC system.

Eksigent and Micro-Tech compete with much more established players in the LC pump market such as Dionex, Waters, and Agilent. The ExpressLC and Ultra-Plus systems are competing with Agilent’s 1100 Series HPLC and Capillary LC systems. The 1100 Series capillary pump incorporates an electronic flow control and can be combined with Agilent’s mass spectrometry products for analysis of tiny samples and extremely low analyte concentrations inherent to many proteomic applications. Comparable systems offered by Waters are the Acquity UPLC and nanoAcquity UPLC. The nanoAcquity UPLC system is optimized for high-resolution separations at precise nanoflow rates and is appropriate for biomarker discovery and proteomic applications. It can be combined with Waters’ Micromass Q-Tof Premier for multiplexed qualitative and quantitative protein expression profiling.

All of these systems are designed to save the user time while at the same time offering higher precision and sensitivity that are key to better comparative proteomic data coming out of LC-MS applications as well as more traditional clinical and diagnostic analyses performed routinely by pharmaceutical manufacturers.

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