Beyond Gels: The Evolution of SDS-Based Protein Separation

The word “technology” implies an improvement on some or all of these aspects – quality, speed, efficiency, and ease. Technologies across all industries have evolved with time, with almost every major stage of evolution significantly changing how we operate in a particular sphere. This article explores the evolution of analytical technologies based on SDS (sodium dodecyl sulfate) for the size-based separation of proteins in molecular biology and biopharmaceutical development.

While easily achieved in 2025 through various techniques, the separation of proteins based on size was once a challenge, posing a massive roadblock in molecular biology research. As a result, the 1960s and 1970s witnessed the development of SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Pioneered by Ulrick K. Laemmli, who leveraged the earlier works of Jake Maizel, Leonard Ornstein and Baruch Davis, gel electrophoresis was one of the first methods developed to successfully separate proteins based on their molecular weight^1,2,3. Interestingly, the initial days of this method involved casting polyacrylamide gels in tubes, which needed to be cracked open with a hammer for the gels to be sliced and dried before staining⁴. Most scientists can’t imagine doing that today, but at that time the method provided a breakthrough in understanding protein-protein interactions. Nearly two decades later, the development of slab gels proved to be a drastic improvement to this method, enabling the analysis of multiple samples⁵. Unsurprisingly, as these methods quickly gained traction within the research community with Laemmli’s work being cited over 300,000 times, SDS-PAGE became the gold standard for separating proteins. From undergraduate students at universities to principal scientists at biopharmaceutical companies, SDS-PAGE continues to be used by many.

Gels Are Good, Capillaries Are Better

Around the same time as the development of SDS-PAGE, Stellan Hjerten worked on developing a new technology called capillary electrophoresis (CE), which was further enhanced by the works of James W. Jorgenson and Krynn D. Lukacs. They successfully demonstrated the separation of proteins and various other biomolecules inside capillary tubes with internal diameters ranging from 3 mm – 75 µM^6,7. The capillary tubes were filled with specific separation matrices. These experiments were carried out under an applied voltage and used a UV detector to gauge separation. This setup alone provided several advantages over SDS-PAGE, including the removal of some manual steps and improved reproducibility. Many findings from these research groups laid the foundation for analytical CE instruments, which were commercially available by the end of the 1980s, and the specific technique for SDS-based separation came to be known as CE-SDS (capillary electrophoresis-sodium dodecyl sulfate). Fast forward to the 21st century, many leading biopharmaceutical companies list CE-SDS as one of their many methods in regulatory filings for commercial biotherapeutics. The widespread adoption of CE-SDS is hardly surprising, given the many improvements it brought about from traditional SDS-PAGE methods⁸. These include, but are not limited to:

• Automation – Pre-filled capillaries eliminate the need for gel casting, staining, and imaging, reducing hands-on time and user variability.
• Higher resolution – Narrow-bore capillaries minimize band broadening, leading to sharper, well-defined peaks.
• Superior reproducibility – Automated separation ensures consistent performance across runs, free from gel-to-gel variability.
• Quantitative precision – Integrated detection provides accurate, reproducible peak integration, unlike subjective band intensity assessments.
• High throughput – Rapid run times enable the analysis of multiple samples in a fraction of the time required for SDS-PAGE.
• Less toxic waste – Removes the need for hazardous reagents such as acrylamide, a neurotoxin required for gel preparation in SDS-PAGE. Automated separation also reduces the need for staining and destaining solutions, leading to fewer reagents and easier waste disposal.

Conclusion

Patients in dire need of life-saving therapies depend on the fast commercial release of therapeutic drugs. With several technological advancements fueling biopharmaceutical development, there is now a tight race to win regulatory approvals. Research and development are best accelerated with state-of-the-art tools that deliver efficiency and quality. This article outlines how CE-SDS on the Maurice system outperforms SDS-PAGE, enabling faster, quantitative, and reproducible separation of therapeutic proteins. From upstream stages to commercial release, CE-SDS provides high-quality data necessary to make informed decisions on product quality. Additionally, as companies strive to reduce their environmental footprint, CE-SDS offers a more sustainable alternative by minimizing reagent consumption and toxic waste disposal compared to SDS-PAGE. This shift toward greener analytical methods aligns with broader sustainability initiatives in the biopharmaceutical industry. Visit any of our resources below to learn more about CE-SDS specifications or its suitability for various molecules or development stages.