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Bringing New Analytical Capabilities to Researchers

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As part of efforts to meet the increasing analytical demands of researchers, SCIEX – a global leader in life science analytical technologies – recently announced the launch of the ZenoTOF 7600 system. The platform is a new accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument with novel electron activated dissociation (EAD) fragmentation and sensitivity that enables the generation of data that has been previously unattainable.

To learn more about the technology behind the ZenoTOF 7600 system and some of the applications that it could benefit, Technology Networks spoke to Joe Fox, president of SCIEX.

Anna MacDonald (AM): How have the goals of scientists changed in recent years? What demands does this place on analytical technologies?

Joe Fox (JF):
We have seen that expectations of science are ever increasing. This past year is direct proof of that, and things need to be done differently moving forward.

Scientists need the ability and flexibility to unlock new, precise perspectives on any molecule, at any time. This understanding will provide access to desperately needed personalized therapies and help them better and earlier diagnose disease. For analytical technologies, it’s clear that incremental improvement is not going to cut it. We need step change in innovation.

AM: Can you explain the principles of Zeno trap pulsing and some of the advantages it offers?

I think our keynote speaker said it best: “Ions are accumulated in the Zeno trap before being pulsed rapidly into the TOF, meaning we can detect up to 20 x more ions. Consequently, each TOF experiment contains more useful MS/MS information, particularly on lower abundance species that were previously undetectable; introducing our customers to a new unprecedented level of sensitivity.”

This significant improvement in sensitivity allows our customers to answer important questions for the most challenging samples in which the limit of detection plays a crucial role, such as single-cell bioanalysis or where specific assays require much lower levels of detection. With this gain in sensitivity, it means precisely answered questions, shorter lead-time for method development and improved overall productivity.

AM: How does EAD fragmentation compare to collision-induced dissociation (CID)?

CID is a soft, thermal fragmentation technique. It often leads to cleavage of most labile sites and results in fewer diagnostic fragments. There is also insufficient cleavage without protonation sites.

In contrast, EAD is fully tunable, reagent free and can be coupled with ultra-high performance liquid chromatography (UHPLC), making it highly effective and widely applicable in small molecules as well as traditional peptides and proteins. Scientists can quickly identify and localize post-translational modifications on proteins, speeding therapy design and development.

For example, in applications such as drug metabolism, EAD localizes phase one or phase two metabolites and provides a level of detail for structural elucidation not achievable before from a single injection. This means that fewer experiments and less sample consumption is needed to get to the answer and provide the chemist with critical information that was not previously available before, addressing “soft spots” in the molecule.

AM: This is the first time Zeno trap and EAD have been combined in a commercial instrument. What new capabilities will this bring to researchers?

Accessibility and flexibility are going to be the true differentiators. By choosing their fragmentation energies and pulsing the ions, scientists can now uncover structural information previously inaccessible; identify post-translational modifications critical to biological drug development; characterize metabolic pathways to assist with patient safety; detect new multi-omics markers to identify disease and more. Getting all this in a single instrument will empower scientists to ask and answer more questions than they could have before.

AM: What applications will benefit most from this technology?

We see the ZenoTOF 7600 impacting scientists across our applications, especially biopharma, pharma, life sciences research, forensics and food and environmental. However, we are also seeing novel applications being uncovered and are exploring those areas with our customers. For example, the sensitivity of the Zeno trap and EAD fragmentation is helping to elucidate important xenobiotics, which otherwise would have been elusive with CID-based fragmentation in studies on metabolite identification for drug metabolism.

Joe Fox was speaking to Anna MacDonald, Science Writer for Technology Networks.