Tracking the components of a biotherapeutic during processing makes up a key area in search of innovation. One method uses ion mobility spectrometry (IMS). To find out more about this method, GEN spoke with an expert: Ching Wu, PhD, president and CEO at Excellims.

Wu describes IMS as “one of the most robust analytical techniques for in-field chemical analysis, broadly used in mission critical tasks, such as explosive screening and chemical warfare agent detection in harsh environments.” Now, high-performance IMS (HPIMS) improves this technology’s separation capabilities and makes it possible to use it with an electrospray ionization source. As a result, Wu points out, “HPIMS can be directly used to analyze nonvolatile compounds and biologics, such as the key components in the biomanufacturing process: organic acids, amino acids, proteins and peptides, carbohydrates, and others.” This makes HPIMS useful for monitoring bioprocessing.

This analytical tool is even more useful when combined with high-performance liquid chromatography (HPLC). “HPLC-HPIMS provides a two-dimensional chemical identification system,” Wu says. “It is powerful due to the complementary nature of the HPLC and HPIMS separations.” This can be used to separate amino acids that are difficult to separate with HPLC alone. HPIMS can also be used to monitor a fermentation process (see Figure 1).

Bioprocessing 4.0 Figure 1
Figure 1. Separating a mixture of seven reference fermentation compounds with IMS. The compounds are: asparagine; glutamine; methionine; mannose; L-glutathione; gluconic acid; and citric acid in 40:60 acetonitrile: water ESI solvent.

An HPLC-HPIMS system can be used at-line in bioprocessing. Currently, such a system can provide results in minutes. Such testing only takes microliters of sample that is filtered, diluted, and injected in the monitoring system.

“Real-time on-line measurement is the future,” Wu says, “where the HPIMS will be directly mounted on the bioreactor and measure targeted chemical and biological components of the broth.”