Benchmarking All‑Carbon Microbeads for Peptide Chromatography: Tested with Diabetes and Weight‑Loss Peptides

Peer‑reviewed in ACS Omega: Matches silica C18 on efficiency, LOD/LOQ, and loading, with stable performance at high pH and 100% aqueous loading—supporting robust peptide analysis and manufacturing.

Figure. Depiction of All Carbon Microbeads packed inside an HPLC column, glucagon-like peptide (GLP-1) analog structures, and representative chromatograms showing peaks of GLP-1 drugs, semaglutide, and liraglutide.

The global demand for glucagon-like peptide-1 (GLP-1) analogs has soared in recent years, fueled by the explosive popularity of semaglutide (Ozempic, Wegovy) and liraglutide (Victoza, Saxenda) for the treatment of type 2 diabetes and obesity. This surge has brought chromatographic purification of these peptides—a critical bottleneck in pharmaceutical manufacturing—under the scientific spotlight, as chemists seek new avenues to boost throughput, purity, and sustainability.

Now, scientists at Millennial Scientific, led by Michael Jack Parente and Balaji Sitharaman, have introduced microbeads composed of graphitic carbon, specifically engineered to withstand the stressors of industrial-scale GLP-1 purification.

Tackling a Growing Bottleneck

GLP-1 analogs are large, amphiphilic peptides often produced in multi-kilogram batches, requiring numerous liquid chromatography (LC) runs for purification and quality control. The purification steps, which must remove a wide variety of impurities and byproducts, rely heavily on reversed-phase liquid chromatography (RP-HPLC)—and specifically on columns packed with tiny particles made of silica C18, the “gold standard.” These materials, however, are prone to breakdown under harsh cleaning conditions, limit operational flexibility, and add to production costs due to their declining performance over time.

“We saw a real need in the field for a stationary phase that could withstand the stresses of modern peptide purification—higher pH, repeated cleanings, and challenging solvents—while also delivering consistent separations,” says Michael Jack Parente, first author of the new ACS Omega study.

GLP-1 Purification: The Industrial Challenge

GLP-1 analogs are large, amphiphilic peptides often produced in multi-kilogram batches, requiring numerous liquid chromatography (LC) runs for purification and quality control. Silica-based C18 columns, the “gold standard” of reversed-phase LC, have limitations: their surface silanol groups can lead to unwanted secondary interactions, their chemical stability falters under harsh pH or repeated cleaning cycles, and attempts to run highly aqueous mobile phases—a common need for peptide separation—result in “dewetting” that causes performance deterioration or even column failure.

Alternative materials have long been explored, from synthetic graphite to inorganic and polymeric media, but silica’s balance of robustness and efficiency has kept it dominant—until now.

New Carbon Microbeads: A Drop-in Upgrade?

In a head-to-head study, Millennial Scientific’s team packed LC columns with their proprietary All Carbon microbeads. It benchmarked them against silica C18 across every metric that matters in a GLP-1 context: plate count, retention time, detection sensitivity, precision, and sample loading capacity. Both semaglutide and liraglutide were used as representative analytes, modeling real peptides in high-demand production.

The new carbon columns not only matched silica C18 in separation efficiency and detection limits, but outperformed it in precision of retention time—a vital quality parameter for consistent pharmaceutical assays. Even more striking was their stability in the conditions that challenge or even destroy silica: the carbon microbeads maintained performance after exposure to pH extremes (1 to 13), ion-pairing agents, and sustained runs with 100% aqueous mobile phases—no “dewetting,” and no loss of resolution.

“After a single chromatographic step with our new columns, crude liraglutide samples saw their purity leap from about 61% to over 96%,” notes the team. This sort of performance hints at not just laboratory efficacy, but real-world durability and practical value on the manufacturing scale.

“Durability and adaptability are crucial,” explains Balaji Sitharaman, corresponding author and President at Millennial Scientific. “By creating a column that doesn’t break down in real-world settings—whether it’s exposed to aggressive cleaning, tough peptides, or 100% water—we’re helping to future-proof pharmaceutical manufacturing as these therapies become even more common.”

The innovation goes beyond the beads themselves. The microbead synthesis harnesses microfluidic droplet engineering, allowing fine control over particle size, porosity, and even surface chemistry—enabling customization for specific industrial or research needs.

"It’s about bridging scientific insight with scalable engineering," Dr. Sitharaman adds. "We are not just redesigning materials for today, but also the discovery, optimization, and manufacturing processes of tomorrow."

Implications for Manufacturing and Sustainability

Longer-lasting, more resilient columns mean less waste, lower production costs, and fewer delays for pharmaceuticals that are increasingly in demand worldwide. The ability to tune the physical and chemical properties of the carbon microbeads also opens the door to customized solutions for other peptides and future drugs.

“This work,” adds Sitharaman, “supported by the National Institutes of Health and National Science Foundation, is a testament to what happens when advanced materials science meets real industrial needs. We are excited by the promise our All Carbon microbead columns hold for a more sustainable and effective future in peptide drug analysis and manufacturing.

Future Directions

The research team is continuing to investigate ways to optimize microbead properties for a wider variety of biomolecules and is scaling up its manufacturing process. Their work suggests that small changes in materials science—like switching what’s inside a chromatography column—can have a significant impact on the availability, affordability, and sustainability of next-generation pharmaceuticals.

As the pharmaceutical industry braces for continued growth in peptide drugs, advancements like these offer timely solutions for scaling up production while maintaining, or even raising, quality standards.

“In the end,” reflects Parente, “we want scientists and manufacturers to have tools that just work—no matter how tough the molecule or the method.”

“Developing scalable and sustainable manufacturing technologies is a priority not just for companies, but for global health,” says Sitharaman. “We believe this platform can help make life-changing medicines more accessible, while also reducing the environmental impact of their production.”

Reference.

Michael Jack Parente, Balaji Sitharaman, Liquid Chromatography Evaluation of a Novel Graphitic Carbon Stationary Phase Using Glucagon-Like Peptide-1 Analogs, ACS Omega, 2025.

Get in touch to discuss how we can support your peptide separation and purification needs. Please email us at inquiry@millennialscientific.com, call us at 855 388 2800, or fill in our online form.