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Accelerating and Refining With Mass Spectrometry

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Charge heterogeneity analysis is a key part of biopharmaceutical development, but a significant bottleneck lies in correlating imaged capillary isoelectric focusing (icIEF) data and mass spectrometry (MS) analysis.

At ASMS 2023, Technology Networks spoke with Dr. Chris Lock, vice president of global research and development at SCIEX, to understand how the newly launched Intabio ZT system can help overcome these challenges and accelerate drug candidate selection.

Tackling key bottlenecks in drug development

The lack of connectivity between icIEF and MS can hinder the identification of unknown charge variants during early drug development. “The correlation of these two sets of data is quite challenging, and it takes a lot of time,” said Lock. “When we started talking with our biopharma customers, they identified this as one of their key bottlenecks.”

SCIEX’s Intabio ZT system, launched at ASMS 2023, can eliminate some of this guesswork. “Now we have a direct correlation between the peaks you've seen in the icIEF separation with the MS analysis, and that's opening up new data and new ways of processing the sample that customers haven't been able to do before,” Lock explained.

This is the first fully integrated, microfluidic chip-based platform that combines both icIEF separation and UV detection, enabling the separation, quantitation and identification of biopharmaceutical charge variants and their proteoforms. The system also reveals new depths of information by employing innovative data processing capabilities within Biologics Explorer software.

“We hear from customers the consistent need to identify developable molecules earlier in the process. To do so, we need multiple pieces of critical data up front. The Intabio ZT system provides mass information on charge variants that has the power to change protein therapeutic development by providing the comprehensive data needed to make quick and confident decisions on the developability of potential therapies,” said Dr. Dominic Gostick, vice president of product management at SCIEX.

Dr. Chris Lock with the Intabio ZT system at ASMS 2023. Credit: Technology Networks

Unique applications and challenges ahead

Another key application using mass spectrometry is the testing of per- and polyfluoroalkyl substances – also known as PFAS, or “forever chemicals” – analysis space. This is a growing area with increasing public awareness, and one in which SCIEX can leverage its expertise. Regulatory bodies are proposing targets for individual PFAS compounds due to health concerns, which requires the analysis of small amounts of material with low levels of background contamination and precise sample preparation. “One of the advantages is that we have quite a lot of experience with our workflow specialists around how to set up the experiments and get the backgrounds low enough to be able to do these really challenging assays,” said Lock.

Building the right tools

Lock also discusses some of the challenges involved in the early stages of drug development. “Speed is one thing that comes up, as well as the volume of samples,” he explained. “As you move towards the idea of personalized medicine and biomarker identification, there are pretty large patient cohorts that you typically want to analyze, so that is a challenge in terms of large-scale data analysis.”

Furthermore, a key theme for SCIEX at ASMS 2023 is “pursuing new paths”, as well as a customer-centric focus to enable discovery and collaboration. Lock elaborated on this point and the importance of collaboration: “How do we actually help the customer solve the problem, like PFAS? Really getting in close with the customer to understand what they’re really trying to do – working with them and making sure we have the right workflow specialists to support them developing their assays on their technology and telling us: What works today? What gaps do we still need to solve?”

Overall, SCIEX is building on its mission to help researchers produce robust, reliable and reproducible analysis and provide solutions for molecule detection and quantitation.

Dr. Chris Lock was speaking to Molly Campbell, Senior Science Writer for Technology Networks, at ASMS 2023.