Technology Forum: Capillary Electrophoresis

What new developments in capillary electrophoresis have you most intrigued?

Preckel: CE has been a viable orthogonal technology to liquid chromatography in the Pharma and Chemical markets. It excels in the area of separation for ions, chiral, polar, and biological compounds (DNA, RNA, proteins) where LC often lacks separation power. Most excitingly, coupling CE to high-end mass spectrometry is an emerging and intriguing application. Another nascent and intriguing application field for CE is label-free fluorescence detection of proteins.

Darling: Over the last few years CE has transitioned from an analytical, research tool to broader application use in the routine analysis and quality control of biotherapeutic drugs, particularly monoclonal antibodies. The maturity of CE as a technique has allowed the incorporation of CE into a routine use environment such that universities are now incorporating CE into their programs and moving away from SDS-PAGE and IEF gel based methods. Another intriguing development is in CE-MS. New high sensitivity and more robust CE-MS interface designs have allowed broader application of this technology for biomarker discovery, monitoring of disease state, and characterization of pharmaceuticals, including intact protein therapeutics. Short analysis times combined with dynamic mass exclusion provide high sequence coverage with CE-MS and positions this technology to provide significant contributions to pre- clinical and clinical applications.

What obstacles stand in the way of capillary electrophoresis development?

Preckel: CE offers the advantage of flexibility and method development options. It accommodates several separation modes, detectors, and can be applied to a broad range of large and small compounds. This flexibility can be seen as intimidating. In recent years, however, standardization and publicly available methods and knowledge base have paved the way to a broader acceptance.

Darling: Next year CE will celebrate 20 years as a commercially available technology. Over this period CE has gained acceptance as a robust, high-resolution methodology in biopharma, however adoption of this technique has been slow across all industries. Existing techniques and methodologies can be difficult to displace due to regulatory concerns and lack of familiarity with CE. Additionally the lack of experienced capillary electrophoresis operators has also impeded mainstream CE implementation. Universities are just now starting to incorporate capillary electrophoresis into their laboratory curriculum and will surely help address some of these concerns.

What is the future of capillary electrophoresis?

Preckel: CE is beyond a stage where the technology is expected to prove its validity. Taking Pharma's shifting focus on large biological molecules and the increasing FDA requirements for orthogonal separation techniques into account, CE has a bright future ahead as an analytical tool.

Darling: We see capillary electrophoresis becoming a mainstream analytical tool with advances in current technology making for easier and more robust applications not only in biopharma, but also in areas such as forensics, food and beverage, biofuels, agribusiness, and other industrial segments.

Industry requirements for reducing product development cycles and increased sensitivity will require advances in all aspects of sample handling and analysis and will be facilitated by innovations in hardware, software, and applications. High-resolution generic method platforms will be integral in reducing method development and providing higher efficiency.

Gomez: I see a bright future for CE but only if the technology and its respective applications are marketed broadly in many scientific disciplines. Certainly, the cost of reagents needed in a typical CE application and speed of analysis are major advantages over other analytical technique. It is good aspects like this that will be a major reason for the future of CE.

Participants

Tobias Preckel

Agilent Technologies

Susan Darling

Beckman Coulter, Inc.

Frank A. Gomez

California State University