Trends and Developments in GC and GC–MS

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Q. What trends do you see emerging in GC or GC–MS?

Christophe Clarysse: The global trends we are seeing and working on with our customers are a desire for miniaturization, flexibility, and faster results. For example, full automatization of sample preparation and multiple detection channels are helping to address the need for more specific and confident results with shorter turnaround times.

In the areas of food safety and environmental health, the number of samples as well as regulatory requirements are always increasing, so this demands a focus on targeted and non‑targeted molecules.

User-friendly data handling solutions that are combined with smart instruments and approaches, including artificial intelligence, are helpful in preventive maintenance, lowering the cost of ownership, and simplifying workflows—essentially bringing turnkey solutions for QA/QC or analytical laboratories.

Eric Denoyer: One trend is the development of smart connected functionality to improve and streamline the user experience. Functions, such as automatic leak checks and troubleshooting diagnostics, allow operators to achieve better results faster, with fewer mistakes. Also, proactively guiding users through preventative maintenance steps helps reduce unplanned downtime and sample reruns, greatly improving productivity.

There is a clear trend to cross‑train operators and a requirement for them to stay connected with what’s happening in several laboratories simultaneously, even when they are not physically in any given one. Remote connectivity is a future trend as an “Industry 4.0” digital transformation sweeps across analytical laboratory enterprises worldwide, driving resource deployment optimization. Smart functionality and remote connectivity are also invaluable when optimizing laboratory operations during a pandemic, especially when laboratory access is limited.

Green chemistry and sustainable operations are also clear trends, and many new instruments are being designed to use less power, water, helium, and other natural resources. We are seeing increased use of recently introduced, cost-efficient, oil-free GC–MS pumps, that run much quieter and cleaner, and eliminate oil spills. Moving applications to smaller, greener, and faster GC systems with efficient direct heating technology, is also a growing trend.

Matthew Edwards: We are seeing an increase in discovery-based approaches, where workflows that are typically seen in the “omics” fields are now expanding to other application areas. Analysts no longer want to simply comply with regulated methods, but also want to see what else is present in their samples. For example, in the automotive industry, manufacturers must adhere to Vehicle Interior Air Quality (VIAQ) regulations, but now also want to be able to monitor other potentially harmful compounds and those which may contribute to malodours.

Chris Rattray: Recent emerging trends in GC and GC hyphenated with MS include an increase in the use of mass spectrometers, especially triple quadrupole instruments, instrument miniaturization, and the migration towards multiclass methods of analysis. The upward trend in the adoption of triple quadrupole instruments is a result of the increased sensitivity and selectivity requirements of challenging multiclass methods, improvements in MS sensitivity, and the reduction in MS pricing. In some cases, detector sensitivity is outpacing instrument and analytical column designs, which should prompt further research and subsequent improvements. Miniaturization of instruments, and the trend toward “black-box” applications continue to surface. These instruments are generally intended to cater to field applications and highly routine operations.

Q. What is the future of GC or GC–MS?

Christophe Clarysse: There is still work to be done around capabilities for increasingly lower detection limits and in the chromatography process itself.

Miniaturization and the need for faster analysis is creating opportunities for chips technology or low thermal mass systems together with new micro-detectors and mass spectrometers.

Portable GC–MS with on-field sampling techniques is the most important growth driver in GC and brings immediate results in various fields such as air pollution or soil analysis.

In classical GC, we observe a global trend towards hyphenated technologies, such as thermal gravimetry combined with infrared (IR) and GC–MS, to characterize advanced materials and microplastics. This “best of both worlds” approach brings more information-rich data to scientists and technicians in a single run.

Eric Denoyer: GC is not going away any time soon. While it is a mature technology, there are still many important applications that depend on GC, such as monitoring climate change, supporting petrochemical processing, and assuring purity of pharmaceuticals from residual solvent residues. However, especially for many food and environmental applications, the future will see more and more GC systems coupled to mass spectrometers. Notably, triple quadrupole GC–MS will be deployed more and more routinely.

In the future, micro-GC will continue to be valued for its convenient small form factor and rapid cycle times. This makes it ideal for “going to the sample”, for example in reaction gas monitoring—an application that is growing, especially as alternative biofuel research is increasingly funded. Also, as natural gas grows in popularity as a fuel source, micro-GC is being used more and more to verify calorific value as a measure of quality and economic valuation.

Matthew Edwards: With the use of GC×GC becoming routine, we are seeing a resurgence in the use of single-channel detectors, such as the simple, robust flame ionization detector (FID) or highly sensitive and selective detectors like sulphur chemiluminescence detectors (SCD). Quality control laboratories that would have previously resorted to MS in an attempt to deconvolve complex samples now benefit from the enhanced separation of GC×GC coupled with single-channel detectors, while in discovery applications, parallel detection is on the rise for fully automated qualitative MS and quantitative FID workflows.

In the cannabis industry, the analysis of terpenes by GC–MS has been particularly problematic. The extreme diversity of the terpene and terpenoid classes, as well as their similar spectra, result in deconvolution difficulties and poor data quality, but physical separation by GC×GC allows confidence in results even with simple FID, as well as a wide dynamic range and robust quantitation.

Chris Rattray: The future of GC and GC–MS will continue to focus on platform miniaturization, reduced analysis times, increased sensitivity, and more rugged chemistries in the sample pathway. For example, electrical and mechanical advances will continue to reduce the size of GC ovens and MS detectors. Reduced analysis times will come by the way of shorter and/or narrower bore columns coupled with a more maintenance‑friendly option to thermally‑resistive column heating, a technology the market as a whole has been unwilling to adopt.

MS will continue to increase in sensitivity, such as lower detection limits, through more efficient generation and transfer of ions. Instrument uptime will be maximized through the development of more rugged surface chemistries and easily replaceable guard assemblies. We also expect to see greater adoption of tandem mass detectors as their price and footprint continues to drop.

Ultimately, the future of GC or GC–MS may be uncertain with the potential adoption of ambient/atmospheric pressure ion sources such as desorption atmospheric pressure photoionization (DAPPI), desorption electrospray ionization (DESI), and/or direct analysis in real time (DART). These ionization techniques are currently applied without the use of a GC system. The future is unclear as to whether or not these ionization techniques will be incorporated with the use of a GC or eliminate the need for a GC system. Until that time, instrument manufacturers will continue to innovate in all the aforementioned areas.

Q. What is the GC or GC–MS application area that you see growing the fastest?

Christophe Clarysse: This tends to depend on which geographies you are talking about. Emerging markets such as India or China see their regulations growing rapidly especially in air and water monitoring, and also in food quality due to globalization, so this is driving GC and GC–MS demand.

Furthermore, pharmaceutical companies have invested a lot in production plants (especially in China, India, and Israel to lower production costs) and require routine QA/QC systems under GMP-regulated environments.

In more mature markets, such as North America and Europe, cannabis and hemp markets also continue to be a growth enhancer for GC as well as food safety and QA/QC laboratories that are expanding their GC and GC–MS use faster than, say, the academic or R&D service areas.

High-throughput systems or fully automated sample handling devices are also in higher demand and generally GC–MS systems have become accepted as an important tool globally as a result of their more specific and sensitive detection capabilities and simplified use.

Eric Denoyer: Detecting nitrosamines in pharmaceuticals by GC–MS has grown sharply this past year as pharmaceutical companies race to assure their products are free of these contaminants.

Air and water quality continue to be recognized as critical, not only to human health, but also to the health of the planet as a whole. This is a growing application area especially in markets such as China and India. As new materials are developed and more commonly used, their presence in air and water are increasing. Detection of perfluorinated alkanes (PFAS) in water is a major growing concern. Microplastics finding their way into waterways and associated biota is also a rapidly growing area of research and regulation development. The recently approved US Senate Bill 1422 in the State of California specifies funding for developing analytical methods for measuring microplastics with an intention to set appropriate regulatory levels over the next several years.

The growing legalization of cannabis worldwide is driving rapid demand for purity and potency analysis. GC–MS Triple Quad (TQ) is an especially popular technique to determine pesticides in plant materials, and demand for this application is growing rapidly. Recent legalization of harvesting hemp as a multipurpose raw material is also driving a growing need to verify its authenticity and freedom from tetrahydrocannabinol (THC) using GC–MS.

Matthew Edwards: An obvious one is the cannabis industry, and this is expected to increase further when regulated testing methods are enforced. We have also seen a rapid increase in biomarker discovery—from samples such as breath, urine, and saliva—in an effort to develop non‑invasive diagnostic tests.

Both application areas will benefit from the adoption of routine, robust, fully automated workflows that encompass everything from sample preparation to data handling and reporting. They deal with high numbers of samples, and automation could help to develop standardized approaches across these industries.

Chris Rattray: Emerging contaminants in the environment as well as the expanding legalization of cannabis are two areas that have seen growth and change in analytical approaches and techniques. While the risk to human health has not been determined for emerging contaminants, scientists and regulatory agencies support research to document these compounds, most notably in drinking water. Brominated flame retardants (BFRs) have gained notoriety given their ubiquitous use in products and persistence in the environment. While cannabis potency is best performed by LC, GC is most suitable for residual solvents and terpene analysis. Cannabis concentrate products such as tinctures, edibles, and oils are extracted in solvents and those products must be analyzed by GC to verify they are free of solvents prior to human consumption. Terpenes are a class of compounds responsible for the flavours and aromas in cannabis. Cannabis growers are interested in determining the ratio of terpenes in different strains for their possible therapeutic effects.

Q. What obstacles stand in the way of GC or GC–MS development?

Christophe Clarysse: We often say that virtually nothing is impossible in GC. Initially designed for small volatile and non‑polar molecules, recent column developments have brought GC and GC–MS into the extended application ranges of polar or larger molecules analysis. As an example, the recent development of thermally‑resistant polar stationary phases, such as ionic liquids, removes traditional barriers. Hence, GC development can no longer be considered in a silo and should be developed together within the application need—including consumables, sample matrix handling, and software solutions.

Many of the recent developments in GC have also brought specific solutions to specific needs or constraints in niche markets such as multidimensional analysis or LC–GC for mineral oil saturated hydrocarbons/mineral oil aromatic hydrocarbons (MOSH/MOAH) analysis.

From a GC-solution-provider standpoint like ours, there is no limitation around GC’s technical capabilities. The challenge is more around seeing research and development return on investment (ROI) for GC solutions that are created to address small/niche markets and realities around what customers are able and willing to invest in terms of innovation.

Eric Denoyer: The ever‑increasing complexity of materials needing to be analyzed by GC or GC–MS poses a real challenge to technology and instrument development. Advanced composite materials are increasingly used in new product design. Just compare today’s tennis racket, road bike, or aeroplane wing to those of 30 years ago.

The complex composition of new materials imparts finely tuned performance characteristics that have to be maintained within tight tolerances. This means that analytes have to be separated from a complex matrix of concomitant material. These more difficult separations require even better chromatography, and place a real constraint on instrument‑size reduction, or throughput improvements. However, the growing use of MS/MS techniques greatly simplifies data for complex mixtures, improving specificity and certainty.

Matthew Edwards: The global shortage of helium has meant that new laboratories struggle to secure helium gas cylinders, so there is a desperate need to develop GC–MS technology that is fully compatible with a hydrogen carrier—ideally with the performance levels we’ve come to expect when using helium.

Chris Rattray: There are some complications in the development of the GC–MS platform, especially if you consider tandem mass analyzers. The past decade has seen the refinement of the gas chromatograph as a platform. Improvements in flow control and rapidly responding thermocouples and heating elements have greatly increased retention time reproducibility for methods with complex temperature programmes. On the other hand, detector sensitivity has been improving by an order of magnitude every few years. There are now single quadrupole instruments available from multiple vendors with sources that are so efficient at generating and delivering ions to the mass analyzer that their sensitivity has greatly outpaced improvements in the inertness of the sample pathway, so most end users are not able to take advantage of this leap in sensitivity.

The inert sample pathway is one major challenge for the consumables vendors. Short narrow columns could be used to reduce the analyte residence time on‑column, which reduces the probability of degradation or adsorption. Faster run times are always desired, however, this raises its own issues. Column selectivity is temperature-dependent, so to preserve the separations we are used to, we would need to be capable of very fast ramp rates, and fast ramp rates require very fast and accurate electronic pressure control.

Q. What was the biggest accomplishment or news in 2019/2020 for GC or GC–MS?

Christophe Clarysse: We have already reached next generation GC–MS. From my point of view, the biggest recent accomplishments in GC have been focused on sample pretreatment before the GC analysis, such as thermal desorption, online analysis, and on-site sampling devices. New detection systems, such as plasma detectors, have also become more popular while many traditional GC–MS/MS applications are beginning to move towards LC–MS/MS as a result of new ionization techniques.

The latest data handling systems have also brought together GC, GC–MS, LC, and LC–MS/MS under the same software platform, making the workflow inside laboratories much more flexible and easier to operate by “generalist” chromatographers.

Eric Denoyer: By far the biggest achievement in 2019/2020 was smart‑connected technology, developed originally for cutting‑edge next‑generation systems, now being extended to mainstream GC and GC–MS systems. The fact that this enabling technology is now available in market‑leading mainstream systems, across high‑end, mid‑range, and micro‑GC platforms, means it will get into the hands of far more people. This is an inflection point in terms of productivity improvement and resource deployment that will have a huge lasting impact on efficiency gains in the analytical industry. As importantly, laboratories are returning to work in split shifts to minimize on-site staff numbers during the COVID pandemic. This means expertise on-site during a single shift is unlikely to be available on all three extended shifts. Smarter instruments help trouble‑shoot faster to get up and running sooner. Remote connectivity helps connect a remote expert to the on-site instrument. These smart connected functions are invaluable as laboratories return to work in a pandemic.

Matthew Edwards: Modern GC–MS and GC×GC–MS instruments allow us to gain greater insight into sample compositions than ever before. Until now, data analysis has remained a challenging prospect. The rise in untargeted “discovery-based” workflows has finally put pressure on instrument manufacturers to develop software that can tackle these huge volumes of data. New software tools are now available to extract meaningful results using all of the raw data, without resorting to hours of manual pre‑processing or complicated statistics—making discovery workflows more amenable to routine labs.

Chris Rattray: The past decade has seen several advances and accomplishments in GC and GC–MS, though the last year was fairly quiet. There aren’t any notable accomplishments in 2019/2020 for GC or GC–MS that come to mind.

Christophe Clarysse is an EMEAI Subject Matter Expert for Chromatography and Mass Spectrometry Solutions at PerkinElmer, Inc.

Eric Denoyer is Associate Vice President, Marketing Gas Phase Separations Division, at Agilent Technologies.

Matthew Edwards is Business Development Manager (Americas) at SepSolve Analytical Ltd.

Chris Rattray is a Senior Scientist in GC Solutions at Restek Corporation.

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