New developments in LC-MS/MS
In their aim to support researchers and clinicians, companies such as Thermo Fisher Scientific are also at the forefront of their own R&D. CLI caught up with Dr Edward Goucher, Senior Manager of Business Development, to discuss their new developments.
In the wake of the COVID-19 pandemic, have there been changes in the clinical research/diagnostic landscape?
It’s quite common to observe numerous technology advances in the wake of a major global event. As governments and corporations scramble, doors open for innovative solutions and commercializations are typically fast-tracked. No truer can be said than that of events unfolding during the COVID-19 pandemic. Regulatory approvals and authorization for treatments and diagnostic assays were mandated for emergency use and many labs pivoted towards mass testing and vaccine development. Notably, some lab developed tests (LDTs) and in-vitro diagnostic (IVD) assays were placed on hold; contract testing and hospital laboratories re-allocated recourses, COVID-19 assays were seen to dominate the daily workload.
At the same time, developments in the clinical research space led to accelerated pathogen identification programmes and vaccine production – alternative technologies such as mass spectrometry (MS) were leveraged across numerous applications. Clinical researchers around the world were using MS to identify the critical markers for detection and monitoring of COVID-19. From metabolite-based targets to protein/peptide markers, our portfolio has facilitated multiple labs and organizations around the world to develop vaccines, progress treatment regimens and provide complimentary detection capabilities of the pathogen.
PCR is considered the gold standard for detection and remained the technology of choice during the pandemic owing to its widely accepted performance and established footprint, though MS data from several Thermo Fisher collaborators suggest comparative sensitivity and scalability.
The post-pandemic (as of October 2022) landscape looks somewhat different and we now see a shift back to routine diagnostics. Laboratories tackling large sample backlogs necessitate – more than ever – a need for high volume testing and automation. This is especially true for many COVID start-up labs which were able to generate substantial revenues and pivot towards alternative diagnostic workflows to sustain growth.
PCR is still considered the gold standard for the detection of COVID-19 but there is a growing sentiment towards monitoring infectious disease panels, placing MS in the spotlight because of its ability to detect large numbers of pathogens in a single analytical run. Future disease outbreaks are inevitable, but experience gained from COVID-19 suggests a much-improved, streamlined approach which will be cost effective and scalable.
How is Thermo Fisher supporting clinical labs in this changing environment?
During the pandemic Thermo Fisher quickly mobilized supply chains, activated research and development resources, and deployed field teams to enable customers to meet the demand for testing around the world. Following on from the pandemic, the infrastructure now in place will futureproof our capabilities to better support our customers.
By leveraging capabilities in sample handling automation and harnessing multichannel liquid chromatography (LC) workflows, we have also addressed throughput challenges and method flexibility across several analytical platforms, including our comprehensive MS portfolio, to better serve our customer needs.
What are Thermo Fisher’s main goals for platform and workflow innovations?
The clinical landscape (research and routine IVD) requires versatile instrumentation that enables the analysis of many types of analytes – from disease biomarkers to drugs of abuse – while providing robust, sensitive and time-saving solutions. Our comprehensive MS portfolio includes capabilities suitable for every lab environment, including LC-MS, gas chromatography (GC)-MS, inductively coupled plasma (ICP)-MS, and isotope-ratio mass spectrometry (IRMS).
Key areas of MS innovation are geared towards greater flexibility and assurance by streamlining software integration and compatibility across our MS portfolio, minimizing hands-on time with automation (sample to result) and leveraging our best-in-class multichannel high-performance liquid chromatography (HPLC) portfolio, thereby reducing time-to-results (sample per minute) – all while maintaining and improving analytical performance of our workflows.
We are placing emphasis on workflow approaches. This allows every clinical laboratory to move beyond the challenge of instrument operation and focus on their end goal that can be achieved via an optimized method or solution that may easily be implemented into a laboratory.
Our comprehensive solutions offer concise pathways resulting in ultimate confidence. For analytical laboratories, purchasing an MS system is the first of several challenges. A user no longer needs a doctorate to operate the technology, an optimized workflow can be customized based on need, an extensive library of molecules for easy detection and identification, and an intuitive, easy-to-use software. For example, we have developed a toxicology pathway that can enable every laboratory around the world (from clinical research and IVD, to forensic and sports anti-doping) to have a ready to go, all-in-one LC-MS/MS solution with a comprehensive compound database (1800+ compounds) and spectral libraries.
As MS continues to evolve, novel front-end technologies that can be readily implemented for everyday use are also coming to practice. We recently launched an automated device for the analysis of dried matrix spots such as urine and blood by LC-MS/MS. This fully automated dried spot autosampler delivers a liquid sample to the UHPLC for online solid-phase extraction (SPE) and LC. Advantages over offline/manual approaches include minimal sample handling and ease of use (e.g. incorporating inline sample clean-up by proprietary Thermo Scientific™ TurboFlow technology).
In parallel, advances in front-end sources also offers streamlined sample introduction with minimal-to-no sample preparation. Paper spray ionization is a direct, fast and low-cost sampling and ionization method for quantitative and qualitative mass spectrometry-based analysis of complex mixtures. The technology provides a streamlined a way to directly inject samples from a filter card or cartridge, saving significant analysis time and money, which in turn helps organizations operate at optimal capacity.
Continued focus on these orthogonal technologies can potentially result in a major change to traditional sample collection strategies which can be uncomfortable and cumbersome – i.e. whole blood venepuncture to DBS (dried blood spot) from a single fingerpick – specifically in areas such as therapeutic drug monitoring, wellness and toxicology, which all benefit from remote sample collection.
LC-MS/MS is a gold standard technology for many assays – what are the challenges in this area and what recent developments has Thermo Fisher made to help overcome them?
Ease of use is always a topic of discussion when we consider the challenges our customers, and the wider community face towards adoption of MS in the clinical lab. Having a single software platform for method development, acquisition and processing increases efficiency and confidence. Integrating that single software solution (across our platforms) ensures operational simplicity and streamlines method transfer and data handling. The availability of commercially available IVD kits supports improved method implementation as well as contributes to regulatory requirements and standardization. Another important consideration is that sensitivity, speed and selectivity of the MS method are continually challenged. For example, analytes commonly observed in low-level endocrinology assays and novel psychoactive panels push technology limits by necessitating low analyte cut-off limits and are challenged further by in-source matrix suppression. The emergence of novel front-end technologies coupled to assays requiring minimal sample clean-up and/or no chromatographic separation bring sensitivity, speed and selectivity of the mass spectrometer to the forefront of the discussion. Notably, our Thermo Scientific™ Orbitrap™ technology can address ultimate selectivity for protein assays and resolve difficult isobaric interferences. In parallel, our new triple quadrupole MS systems are the fastest currently on the market with regard to single/multi reaction scanning and positive/negative switching. This offers significant advantages towards rapid analysis of large panels at the maximum possible sensitivities.
This year’s American Association of Clinical Chemistry (AACC) meeting was the most ‘normal’ for a couple of years, what does it mean to Thermo Fisher to be able attend in-person?
We were certainly excited to attend AACC and it was a welcome change for everyone involved to participate in-person. How else would we enjoy the “windy city”! Navigating the event in-person held tremendous value; it’s one of Thermo Fisher Scientific’s key annual scientific meetings which allows the opportunity to connect with colleagues and customers around the world.
During the event we showcased our capabilities in clinical mass spectrometry including our automated dried spot sampling and analysis UHPLC system, our all-in-one LC-MS/MS solution for toxicology [available in either high-resolution accurate-mass (HRAM) Orbitrap or triple-quadrupole (QqQ) options], our medical device portfolio of LC-MS systems while also highlighting product lines across our organization suitable for all our clinical customer needs. Examples include, but not limited to, allergy and autoimmune testing, quantitative PCR and reproductive health. With over 350 colleagues attending in-person, four workshops, and numerous posters, this goes to show our level of involvement and dedication towards clinical chemistry.
We look forward to regional AACC events through the remainder of the year, and of course next year’s annual meeting in Anaheim, CA, USA.
What does the company see as the next big challenges on the horizon?
The continuous growth of complex diseases and the demand to learn more about every patient ahead of time not only requires development of better analytical tools, but also has been encouraging governments across the world to consider better management of laboratories. This includes the test kits and instruments they use to monitor patients on a daily basis. Therefore, several countries have mandated the use of approved IVD instruments and kits for detecting and moni-
toring diseases in humans.
In 2019, Thermo Fisher Scientific registered its LC-MS medical device portfolio* with the U.S. FDA. These medical devices help to enable clinical diagnostic laboratories to develop and optimize their LDT and IVD assays, which can be used for monitoring patient samples. With regulatory requirements varying across the world, it is useful for our customers to know that our open LC-MS medical device platforms are registered with the FDA, self-declared as IVDD, and listed in 29 countries across the globe.
The past decade has seen significant improvements in the development of mass spectrometers and chromatographic front-ends. And our customers and collaborators have been using various MS platforms for many years to solve several critical issues in clinical research and diagnostics. While the list continues to grow, the demands and expectations from the users will also streamline the future evolution of this technology. Reducing the size and cost to operate, enabling MS into point-of-care (POC) and real-time surgical settings, expansion of clinical MS applications for the targeted analysis of proteins and peptides, all while improving ease of use and implementation, are critical factors to enabling the exponential growth we are witnessing of MS in the field of laboratory medicine.
Dr Edward Goucher PhD, Senior Manager, Business Development
Thermo Fisher Scientific, Hemel Hempstead, UK
Thermo Fisher Scientific products are distributed globally so uses, applications, and availability of product in each country depend on local regulatory marketing authorization status.