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Q&A with Orbitrap Astral Team

What was your role within the team?

Hamish Stewart: I was the lead scientist, essentially I defined, integrated and tested technologies, guiding the engineers who spun ideas into physical reality. In practise this involved a great deal of communication, even more troubleshooting, and going door to door complaining about whatever issue would come up in the day.

Christian Hock: As the technical lead, I was involved in all aspects of the technology. Over the years my most important tasks were to grow the team, maintain oversight, and ensure that the team focused on the right priorities.

Daniel Hermanson: I am the Senior Product Marketing Manager within the team. I am responsible for working with the team to develop customer facing content and providing internal training on the instrument to our global teams.

Alexander Makarov: I initiated and led this project through to its late-stage development, after which I remained involved as a consultant for instrumentation design.

What were the biggest challenges in this project?

Hamish Stewart: There were a great many at different stages, and we take some effort to identify and rapidly mobilise to address important problems as they arise. Perhaps most notably we were blindsided by the complexity of the instrument control hardware and software, assuming that a modular approach with multiple synchronised control boards, PCs, USB and custom networking, would hold fine as we pushed repetition rates from ~40 to 200 Hz. The thing fell flat on its face, taking man-years of software engineering to make both fast and stable.

Christian Hock: The biggest challenge was staying focused and resolving critical issues in a timely manner.

Daniel Hermanson: The development of novel technology presents significant challenges in both realising it as a real commercial product and communicating how to utilise the novel technology to improve capabilities in the real world.

Alexander Makarov: Every part of the mass analyser — including the injection optics, ion mirror, and detection system — had to be invented and developed from scratch to achieve unprecedented levels of performance, and carefully matched to one another to meet the demands of real-world applications. This performance then had to be maintained across hundreds of serial instruments following the enthusiastic adoption of the Orbitrap Astral mass spectrometer by the -omics community.

What different strengths did different people bring to the team?

Hamish Stewart: It can't be overstated how many disciplines and functions come together to create an analytical instrument. A proof of concept may be obtained with a small team of good scientists with mechanical, electronic and software engineers, but the real thing requires a large organised group, with a vast diversity of knowledge and backgrounds that often belie the more uniform job titles.

Christian Hock: Having an extremely skilled and diverse team capable of effective communication and collaboration was crucial.

Daniel Hermanson: The team consists of individuals across multiple functions and backgrounds from multiple countries. The major strength of the team is that each of these individuals contributes their respective expertise in a synergistic way.

Alexander Makarov: Only a great and versatile team could deliver the success of such a complex and long-term project. Every conceivable skill is needed at the highest level — from theoretical physics and biochemistry to machine learning and management. Fortunately, we were able to build such a team over the years, and we must continue developing it to tackle the challenges ahead.

Why is this work so important and exciting?

Hamish Stewart: This is the most significant technological advance in mass analysers in two decades. The high sensitivity allows deep investigative studies of single cells that only a few years ago were considered impossible, while the high throughput and dynamic range enable, in tandem with sample preparation advances, bioanalysis software, and the introduction of biobanks, analysis of large patient cohorts far beyond what could previously have been performed. The promises of precision medicine, treatment tailored to a deep understanding of each individual patient, seem tantalisingly close.

Christian Hock: Shortly after its introduction, the instrument became an invaluable tool for the scientific community, aiding in the resolution of critical challenges facing humankind.

Daniel Hermanson: The Orbitrap Astral mass spectrometer represents a significant step forward in performance across multiple applications. It is inspiring to see the instrument be put into practice to help solve significant questions in the real world, delivering on our mission to enable customers to make the world cleaner, healthier, and safer.

Alexander Makarov: Orbitrap Astral mass spectrometer comes exactly at the tipping point in translational proteomics. On one hand, advances in chromatography and AI/ML for data processing have removed bottlenecks at both the front and back ends of mass spectrometry; on the other, the importance of proteomics is increasingly recognised by the post-genomic community. Now, this instrument gives mass spectrometry a significant boost, both in depth of analysis and in cost-per-sample.

Where do you see the biggest impact of this technology/research being?

Christian Hock: Cancer research and life science research in general.

Daniel Hermanson: I think the biggest impact of the Orbitrap Astral mass spectrometer has been on the speed and depth at which questions can be answered. Since the inception of proteomics the mass spectrometer has been the rate limiting step in the workflow, but now we have significantly advanced the throughput capabilities such that this may no longer be the case for certain experiments.

Alexander Makarov: I see the greatest impact of this technology in translational proteomics, as well as in advanced research areas such as single-cell proteomics, deep visual proteomics, immunopeptidomics, cross-linking, etc.

How will this work be used in real life applications?

Daniel Hermanson: It has been amazing to see the Orbitrap Astral mass spectrometer be put to use in real life applications across many different disciplines and approaches. With well over 200 pre-print and peer-reviewed publications since the instrument launch the instrument has positively impacted numerous proteomics, metabolomics, and biopharma applications.

Alexander Makarov: We see that, with this technology, we can now conduct medium- and large-scale clinical studies with unprecedented depth and quantitative accuracy, offering new insights into disease and the effects of novel treatments.

How do you see this work developing over the next few years, and what is next for this technology/research?

Hamish Stewart: This is only the beginning. Orbitrap-based instruments started out as similar large, heavy and high end mass spectrometers, but were greatly improved first in performance, but ultimately in simplicity and elegance, becoming instruments accessible to regular labs and with tens of thousands produced. With the Astral analyser there is enormous room for performance enhancement, but also I hope for democratisation.

Daniel Hermanson: With the step change in performance of the Orbitrap Astral mass spectrometer has shifted the needs of the workflow around the mass spectrometer, particularly with the need for further sample preparation automation and data processing strategies to handle large data sets. The development of these connected pieces are important for the growth and application of the technology.

Alexander Makarov: I believe there is still considerable potential to improve the performance of mass spectrometry — I hope to see another tenfold gain in sensitivity within this decade!

What inspires or motivates your team?

Christian Hock: Continuous learning, driving innovation, and growing as a team.

Daniel Hermanson: The work that our customers do with the Orbitrap Astral mass spectrometer is a huge inspiration to the team. The development of technology is a long process and we have a general sense of the performance for key applications, but ultimately the success in the real-life applications needs to be proven. It has been amazing to see how our customers have taken the technology and applied it to solve meaningful scientific problems.

Alexander Makarov: The main motivations are team spirit, the ability to innovate and fulfil one’s potential, as well as the positive feedback from enthusiastic customers and management.

What is the importance of collaboration in the chemical sciences?

Christian Hock: Collaboration is key in science. Sharing knowledge and collaborating on all levels is invaluable.

Daniel Hermanson: Collaboration is essential for success in any scientific endeavour. The best science occurs when different perspectives are embraced to create synergistic value, propelling ideas and experiments to new heights.

Alexander Makarov: Collaboration is key in science, but even more so in technology! Only by working together like a grand symphony orchestra could we play a masterpiece of innovation and transform an idea into a serial product.

What does good research culture look like or mean to you?

Christian Hock: Involvement and intensity are crucial. Involvement is essential for the entire team to contribute to innovation, while intensity ensures that critical challenges are resolved in a timely manner.

Daniel Hermanson: A positive research culture embraces different perspectives and backgrounds to extend ideas into practice. There are many diverse skills and views that should be taken into account to ideate and realise the best research.

Alexander Makarov: A good research culture demands self-motivated innovation, openness to feedback from both people and nature, perseverance in the face of adversity, and deep collaboration within the team.

How can scientists try to improve the environmental sustainability of research? Can you give us any examples from your own experience or context?

Hamish Stewart: I'm fortunate to work in an area where technological improvement goes hand in hand with sustainability. Introduction of advanced pump technology for example, cut the Orbitrap Astral's power consumption in half, with knock on reductions in air conditioning costs. Meanwhile its high throughput let's it perform the job of several lesser instruments, with major ensuing reduction in energy, space, solvent use etc.

Christian Hock: We are using ‘oil-free’ vacuum pumps in our instruments. This reduces power consumption to 50% and omits usage of oil and oil replacement.

Daniel Hermanson: We have specific programs to improve the environmental sustainability of our instruments and processes. One critical outcome of this is that the Orbitrap Astral mass spectrometer consumes 40% less power than previous generation instruments due to the implementation of an oil-free vacuum pump. We also have initiatives that reduce packaging waste and utilise renewable energy sources within our Bremen facility.

Alexander Makarov: We aim to address this in instrumentation by using lighter, more compact designs, low-energy dry pumps, multi-stage turbopumps, recyclable packaging, and life-cycle planning. It requires significant additional design effort, but we believe it is well worth it!

What advice would you give to a young person considering a career in the chemical sciences?

Christian Hock: Pursue your goals, look out for a mentor, and most importantly, stay motivated even if you hit roadblock.

Daniel Hermanson: I would recommend to always be an active learner. Knowledge and skills are built upon experiences and learning cumulatively, so exploring new disciplines and trying new things is extremely important to both find your passion and strengths but also to understand weaknesses and different perspectives.

Alexander Makarov: Formulate your goals and dreams, pursue them with determination, maximise networking with others, and always take any feedback you receive from people or nature very seriously.