Recent Trends and Developments in Sample Preparation

LCGC International spoke with Marco Wolff, Product Manager of Automated Sample Preparation at Gerstel; Lauryn Bailey, Vice President of Global Marketing Strategy & Product Management at Phenomenex; James Edwards, Chromatography Manager at Porvair Sciences Limited; and Arielle Cocozza (in collaboration with Emily Eng and Stephanie Haviland), Technical Specialist at UCT.

What trends do you see emerging in sample preparation?

Wolff: More laboratories are automating their traditional manual workflows. A lot of laboratories still rely to some degree on manual sample preparation, but tough competition is bringing about further consolidation in the contract analysis business. This results in critical mass being reached in the form of sufficient numbers of samples for each laboratory to warrant investment in automation. Cost is always a key driver, but new requirements for sustainability and environmental impact reporting mean that the pressure is on to improve in these areas. The pursuit of “green” analytical practices is characterized by a reduced reliance on potentially toxic reagents and solvents. This movement aligns with both environmental concerns and the pragmatic goal of lowering cost-per-sample, both of which can be realized by miniaturization, which goes together with automation.

Laboratories are actively seeking methods to streamline and optimize sample preparation workflows to achieve sustainability goals while enhancing precision, accuracy, and efficiency in laboratory processes.

The current shortage of qualified laboratory staff also provides a further boost to the automation trend. Automated systems increase efficiency and provide assured productivity, while freeing up scarce qualified staff for more important tasks. This shift towards automation aligns with the broader industry goal of maintaining high-quality analytical standards while adapting to the evolving landscape of workforce availability.

Of course, not all analytical work is performed by contract laboratories. For example, many companies require in-house capabilities for quicker turnaround to support their production. Such typically smaller laboratory organizations are also finding it hard to compete for qualified personnel and a growing number are seeking comprehensive solutions for specific analytical questions, such as, for example, determination of production contaminants like 3-monochloropropane-1,2-diol (3-MCPD) in food or of environmental pollutants like per- and polyfluoroalkyl substances (PFAS). There is a discernible shift toward complete packages that include not just the device, but also the application and qualified support to ideally implement a new application out of the box.

Bailey: There are multiple key areas that will be trending in sample preparation. For one, there is a demand to achieve lower detection limits. This could be because of stringent regulations, for example, PFAS tolerance limits or a reduction in sample sizes, such as drug metabolism and pharmacokinetics (DMPK) assays in drug development. Either way, these types of applications will require sample concentration or alternative approaches to sample preparation to achieve the detection requirements with the available sample size. A solution to this is “fit-for-purpose” sample preparation solutions, designed with specific analytes in mind to enable laboratories to achieve the results they demand. Second, there is a demand for automation and improved laboratory efficiency. Sample preparation has been a notoriously manual process, so there continues to be a drive to driving efficiencies either through better processes (fewer steps), integrating into automation platforms to increase throughput and improve reproducibility and accuracy, or both. Finally, there are demands for sustainability and less waste. Sustainability and managing the environmental impact are becoming increasingly important, and sample preparation techniques can often be very high in plastic and solvent waste. As many companies focus on sustainability and reducing their environmental footprint, we will start to see sample preparation techniques evolving to result in less solvent usage and overall waste for laboratories.

Edwards: One of the trends I have observed is the growing emphasis toward greener sample preparation. Given that sample preparation often involves the use of organic solvents, there is a clear opportunity for scientists to adopt more environmentally friendly practices. Several ideas have been proposed to achieve this, including substituting harmful solvents, reducing sample and solvent volumes, and implementing more reproducible processes that require fewer replicates or retests.

Cocozza: Recent advances in liquid chromatography–mass spectrometry (LC–MS) technology have had a significant impact on sample preparation. The high resolving power and sensitivity of these instruments have greatly influenced trends in sample preparation, leading to a greater emphasis on automation, method consolidation, and sample size reduction. One notable trend is the miniaturization of sample preparation processes, which have been facilitated by using smaller sample sizes. This approach has not only enhanced laboratory efficiency, but it has also enabled the analysis of more complex samples that were previously challenging to analyze. By reducing the amount of sample required for analysis, researchers can optimize time and resources while obtaining more accurate and precise data.

In your opinion, what is the future of sample preparation?

Wolff: The future of sample preparation appears exceptionally promising, particularly considering challenges faced by analytical laboratories. The key to addressing these challenges lies in automation, a transformative force that not only streamlines workflows, but it also ensures consistent and reliable results.

Laboratories are increasingly recognizing the indispensable role of automation in overcoming the complexities associated with sample handling. By leveraging advanced robotics and intelligent software, laboratories can achieve a level of precision and repeatability that is challenging to attain through manual methods.

One notable advantage of automated sample preparation is its ability to facilitate “good” analytical work, including sample preparation, without adding personnel. “Dilute and shoot” methods, while suitable for some straightforward analyses, face limitations as questions become more complex or sample matrices more intricate, even with the advent of increasingly sensitive mass spectrometers. In such cases, automated sample preparation becomes indispensable to ensure reliable and robust results.

Undoubtedly, a crucial part of the future of sample preparation is software. To be successful, laboratory solutions will need “user-friendly” rugged software for both system control and data analysis. Integrated software solutions will continue to streamline laboratory operations from sample logging to data reporting, increasing the overall efficiency and effectiveness of analytical workflows.

Laboratories are increasingly demanding intuitive software interfaces that allow for easy and user-friendly operation of analysis systems. This ensures that even users with varying levels of expertise can navigate and utilize these systems effectively, minimizing the learning curve.

Moreover, tailored data analysis software designed to address specific analytical questions will be in demand. Customized analysis software will streamline data interpretation and accelerate decision-making processes. Even non-skilled production operators will quickly be able to get go/ no-go results from a laboratory instrument. An additional benefit is the reduction in the need for software training. Laboratories can streamline their onboarding processes as user-friendly interfaces and task-specific analysis tools become more widely used. This saves time and resources while allowing the laboratory staff to focus on their core responsibilities and get the job done.

Bailey: Sample preparation is moving away from a one-size-fits-most approach and back to a targeted approach. The future is workflow-specific solutions that are designed for targeted analytes and compound classes rather than a “catch-all” approach. This is because the demand for accurate results is paramount, and these targeted workflows will ensure the most accurate results for a targeted assay.

The future of sample preparation will also be a simplification through innovation. Future techniques will take added steps and added waste out of the sample preparation process to deliver the results the laboratory needs more sustainably and in less time.

Edwards: The future of sample preparation is likely to revolve around workflow automation. Automation aligns with the principles of green sample preparation by enabling more accurate work with smaller volumes and minimizing human error. Due to this increased accuracy at smaller volumes, we can also expect sample preparation methods to shift towards smaller bed weights to allow analysts to be able to reduce the volume of solvents and sample they use.

Cocozza: Automated systems for solid-phase extraction (SPE) seem to be a trend for laboratories to prepare more samples simultaneously. There is a need for high throughput and streamlined processes while maintaining consistency and quality. With new regulations for testing, the volume of samples rises while laboratories are tasked with doing more with less. This means less labor, less bench space, fewer consumables, faster workflows, and a greater emphasis on automation without sacrificing quality.

To meet these expectations, laboratories are moving towards quick, easy, cheap, effective, rugged, and safe (QuEChERS) for food matrices, micro solid-phase, and SPE. Using QuEChERS eliminates the need for large sampling volumes, large amounts of bench space, and bulky extraction equipment. Another benefit this provides is it uses less solvent and encourages environmentally friendly practices, leading to the development of greener sample preparation methods with reduced solvent waste generation.

What obstacles do you think stand in the way of sample preparation development?

Wolff: Obstacles hindering the development of automated sample preparation are notably linked to outdated standards and norms. These often fail to consider the potentialof automation, for example requiring large sample volumes that are neither conducive to automation nor necessary with appropriate miniaturization. An example is the requirement for a 250-mL water sample to determine PFAS levels, when 1–2 mL would be sufficient.

Another obstacle is the lack of standardized communication interfaces between hardware and software. The lack of standardized communication interfaces poses a problem when creating integrated systems that incorporate solutions or devices from various manufacturers. The absence of standardized interfaces complicates the seamless interoperability of different components within a comprehensive system. Standardizing these interfaces would greatly facilitate the development and integration of comprehensively automated sample preparation systems.

Furthermore, obstacles emerge in the form of customer expectations when looking for sample preparation solutions. On the one hand, there is a growing demand for complete, turnkey solutions that encompass every aspect of an analytical application, including sample preparation. On the other hand, solutions must be designed with an openness that allows for customization to accommodate specific customer requirements. This customization can vary widely, from changes in sample quantity and matrix to adapting to different analysis systems and chromatography data systems (CDS). Striking the right balance between providing a pre-packaged solution and maintaining the flexibility for customization remains a pivotal challenge for suppliers.

Bailey: The ever-evolving needs of the life science industry is the biggest obstacle we face in sample preparation solution development. First, there are emerging analytes of interest. From emerging contaminants to novel drug therapeutics, the scope of the molecules researchers need to analyze is continuously changing. Sample preparation needs to keep up with those needs. Second, project timelines are getting condensed. Now more than ever, we want to get test results immediately, or drugs to market faster. This means that researchers are working hard to accelerate time to results. Sample preparation techniques need to align to these industry timelines.

Edwards: Two main challenges come to mind. First, there is a time investment required for proper sample preparation. Some individuals may perceive this investment as not worthwhile, but inadequately prepared samples can lead to issues during analysis. These issues include increased instrument maintenance, more frequent sample retesting, and complex baseline interpretation. Second, there can be a disconnect between academic and industry partners, making collaboration on effective sample preparation solutions more challenging.

Cocozza: As instrumentation becomes more specialized and sensitive, analytical equipment, such as quadrupole time-of-flight MS (QTOF-MS) and high-resolution MS (HRMS) instruments, may hinder new development from a financial standpoint. The substantial upfront investment required may be out of reach for some laboratories despite their ability to complete preparations sufficiently. Beyond initial costs, ongoing expenses for maintenance and servicing, along with the need for specialized training programs, contribute to the cost factor. The complexity of the operation, potential compatibility issues, and the education for personnel required add to the analytical challenges. Regulatory compliance requirements become more stringent as the analytical methodology advances, creating more hurdles for laboratories developing analytical methods.

The second challenge pertains to the ongoing expenses associated with the purchase and maintenance of robotic automation systems. Although benefiting from the efficiency gained by automation, laboratories can encounter many issues related to day-to-day use. As these systems are utilized consistently, the chances of unexpected failures are bound to occur. Laboratories tend to have solvent-laden air, which can contribute to circuitry failures. In high-throughput preparation environments, there is also rigorous handling by technicians, sample matrix interference, or degradation of consumables that can contribute to automated systems not performing at their optimal capability. To mitigate the risks of downtime and ensure the uninterrupted operation of critical processes, laboratories find themselves compelled to purchase instruments in duplicate.

What was the biggest accomplishment or news in 2023–2024 for sample preparation?

Wolff: The most noteworthy accomplishments and developments in sample preparation in 2023 and 2024 are a mixture of technological advances and a revival of collaborative initiatives.

One outstanding development is the growing support for initiatives aimed at establishing open standards for manufacturers of laboratory equipment. Worldwide acting companies are demanding standardized communication interfaces and data standards. Notably, the laboratory automation data standard (LADS) has gained prominence, leading toward the development of standardized interfaces between laboratory instruments from different companies. Other communication and data standards, like SiLA 2, the Allotrope Data Format (ADF), and Analytical Information Markup Language
(AnIML), contribute to this development. These initiatives reflect a collective commitment to overcoming interoperability challenges and promoting seamless integration between different laboratory technologies.

In this context of standardization, the inauguration of the Future Lab at the IUTA Institute in Duisburg, stands out as a milestone this year in Germany. This visionary endeavor, embedded in a long-term project, showcases how the future laboratory could look in a meaningful way.

As the world has emerged from the challenges posed by the Covid-19 pandemic, the analytical community has returned to in-person meetings, conferences, and trade shows. The post-pandemic era has seen a revitalized enthusiasm for face-to-face interaction. Combined with the benefits of electronic exchanges through online meetings, a hybrid approach is establishing itself that maximizes the advantages of both. This adaptive approach reflects the resilience and forward-thinking spirit of the analytical community, ensuring continued knowledge exchange and collaboration in a dynamic and evolving landscape.

Bailey: There are multiple accomplishments in sample preparation in 2023. First, 2023 saw an introduction of more “micro” solutions. From pipette tips to micro-cartridges, solutions are coming to market to enable researchers with limited samples. Second, there was an increased focus on automated solutions. A number of automated or automation-enabled sample prep workflows have been developed, allowing researchers to increase their sample volumes and productivity, allowing for resource savings (time and personnel). Finally, the year saw novel solutions developed for specific workflows. Sample preparation innovations are now taking the scientists’ end goal in mind, so more solutions are surfacing to meet the specific needs of the laboratory to deliver the most confidence in their results.

Edwards: I would say the increased discussion around green sample preparation. While attending conferences, I have noticed an increasing trend of conversations centered on this topic. Considering the significant environmental impact of laboratories, it is crucial to address this area and seek opportunities for improvement.

Cocozza: The Business Research Company recently released its Sample Preparation Global Market Report, which projects that the market will see significant growth over the next few years. According to the report, the market is expected to reach $12.79 billion by 2028, with a compound annual growth rate of 8.1%. Although this is not a groundbreaking innovation in sample preparation, this report emphasizes the ongoing importance of this process in various scientific disciplines and highlights its sustainability in the future. It’s worth noting that even as we try to streamline and automate the process, sample preparation remains a crucial aspect of many scientific experiments.

About the Interviewees

Marco Wolff is Product Manager of Automated Sample Preparation at Gerstel.

Lauryn Bailey is Vice President of Global Marketing Strategy and Product Management at Phenomenex.

James Edwards is Chromatography Manager at Porvair Sciences Limited.

Arielle Cocozza is Technical Specialist at UCT, Inc.