Chromatography consists of separation techniques based on molecular differences such as size, charge, polarity, solubility, affinity, etc. In chromatography, there is a mobile phase and a stationary phase within a column. The mobile phase typically consists of a mixed solution containing the target analyte to be isolated and purified or detected. The stationary phase consists of resin, which is designed to separate the molecules by retaining them for different periods of time. Resins, also referred to as separations media, exist in a wide variety of types, volumes and grades. There are many different ways for the stationary phase to retain analytes inside the column, including reverse phase, normal phase, ion exchange, size exclusion chromatography, affinity, etc.
Mixed-mode chromatography involves the usage of more than one separation mode. The most popular combination is reverse phase and ion exchange methods. In reverse phase, a polar mobile phase and a non-polar stationary phase are used for column separations. Meanwhile, ion exchange separations utilize ionic attraction and repulsion between charged species. The combination of these methods allows the separation of both polar and non-polar analytes in a single column.
The biggest advantage of this method is that users can fine-tune separation selectivity by adjusting several conditions such as mobile phase ionic charge, pH and organic/non-organic solvents. The mixed-mode approach has been evolving from mixed packed beads to single ligands, which yields homogeneous and reproducible results. The zwitterionic ligand is the next generation of mixed-mode separation and includes both anionic and cationic functional groups in each ligand. The mixed-mode technique is commonly used in the pharmaceutical and biotechnology sector to analyze and purify biomolecules. Companies in this end-market mainly drive demand for mixed-mode chromatography resins, but other industries that focus on the production and purification of biomolecules, such as CROs, are involved in the market as well.
The largest market by application for mixed-mode chromatography is in mAbs analysis and purification. In this application, mixed-mode resins are most commonly used to remove host cell proteins, antibody aggregates and excess proteins. Aside from mAbs, mixed-mode separation is also used to purify recombinant proteins, viruses, enzymes, biosimilars and vaccines.
The overall mixed-mode chromatography market, which includes prepacked columns and resins, reached more than $100 million in 2019. Growth in 2020 is projected to be almost flat as the pandemic has significantly diminished general chromatography demand due to lab closures. On the bright side, COVID-19-related research also buoys mixed-mode chromatography demand, particularly for virus and vaccine applications. In the long run, the mixed-mode market will restore its robust growth in 2021 and 2022, driven by pent-up demand and increasing biotherapeutic interest.
The market has a strong base in North America and Europe, supported by significant demand from advanced research labs and biotech giants established in these regions. However, emerging markets such as China and India will lead regional growth, driven by substantial investment in the biotech and biopharma industries in these countries.
In terms of vendor share, Cytiva, formerly known as GE Healthcare before Danaher's acquisition (see IBO 2/28/19), is the leading supplier in the market. The company has a diverse portfolio of mixed-mode resins that cover all of the aforementioned applications. Cytiva also has one of the largest total portfolios of resins designed for vaccine development. Meanwhile, MilliporeSigma has a narrower range of resins, which are targeted primarily towards antibodies and proteins. On the column side, Thermo Fisher Scientific and Waters are the leaders in supplying mixed-mode HPLC columns.