Routine analysis laboratories play a vital role in safeguarding integrity across a wide range of sectors, from food and beverage to forensic and pharmaceutical. With product safety and reliable decision-making on the line, these laboratories must balance productivity with the highest standards of analytical accuracy. Yet, for laboratories operating at or near capacity, or planning to grow their market share, scaling-up workflows without compromising on quality can be challenging.
Liquid chromatography (LC) technologies, including high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC) platforms, support a large proportion of routine analysis workflows. However, these systems can be a major source of inefficiency and serve to limit operational productivity. In particular, issues with the adaptability and resilience of aging LC equipment can be highly disruptive to workflows, making method transfer complex and increasing the need for time-consuming manual steps. Poor platform flexibility and robustness can also leave processes vulnerable to human error, resulting in the need for additional efforts to document out of specification results. This article considers common productivity bottlenecks in routine analysis laboratories, and explores how modern LC technologies and laboratory informatics software are helping businesses overcome them.
Common Productivity Challenges in Routine LC Analysis Workflows
Routine analysis laboratories may face several potential productivity challenges with regards to their LC workflows. One of the most common sources of inefficiency is the process of transferring LC methods between instruments, where unforeseen complications and delays can divert time away from testing and have a major impact on productivity. This is true not only when transferring methods between laboratories, such as from analytical development to quality control (QC) settings, or when outsourcing to contract laboratories, but also when scaling-up methods across multiple instruments within the same laboratory or transferring workflows from legacy to new systems.
The ease and speed of method transfer often depends upon several factors, including the robustness of the method to be transferred, as well as the instrumental deviations of the systems involved. Here, the technical characteristics of the platform, such as gradient delay volume, pump mixing mode, hydrodynamic behavior, choice of column and eluent thermostatic options, can all affect critical performance outcomes, such as peak resolution or retention times. The complexity of method transfer is also determined in large part by the requirements of the analytical outcome and defined limits of acceptable deviation from the original system. Ideally, method transfer should occur with no method modifications to avoid spending large amounts of time and resources re-validating methods.
Other important causes of low productivity often stem from small yet critical oversights during routine laboratory processes, which can have major consequences for operational success. For example, poorly-maintained eluent levels will cause sequences to stop mid-run if there is insufficient solvent to complete an analytical sequence, resulting in the loss of samples, sample re-analysis, and if working in a regulated environment, documentation for regulatory authorities. Compromised HPLC systems are also a key source of laboratory inefficiency, leading to unreliable and out-of-specification results that take valuable time out of routine workflows and prevent laboratories from achieving optimal productivity. Equally, recognizing these performance issues too late can result in extended instrument downtime due to unscheduled maintenance.
Driving Productivity Through Flexible HPLC Technologies
With productivity now a key focus point for analysis laboratories across all sectors, instrument vendors have responded by developing HPLC technologies designed to overcome these challenges.
One of the main reasons why method transfer can be so time-consuming is that success is often not defined by a single instrumental parameter: factors such as gradient delay volumes, column thermostatting and system dispersion effects all play important roles. Poor system configurability through rigid instrument design can, therefore, be a major stumbling block. Fortunately, recent years have seen a heightened focus on increasingly flexible HPLC technologies that can help laboratories streamline method transfer through the application of highly customizable parameters.
Some modern instruments now offer a wide range of customizable features to facilitate the precise replication of existing methods. Highly flexible platforms, such as the Thermo Scientific Vanquish Core HPLC system, for example, allow gradient delay volumes to be seamlessly adjusted to match the analyte retention time and separation profiles of other instruments. Other innovations, such as a choice of still-air and forced-air thermostatting techniques within the same instrument, can help analysts more easily mimic legacy HPLC systems to achieve the desired results faster.
Another key issue associated with method transfer relates to system dispersion effects. While lower system dispersion benefits overall separation power, it can lead to undesirable peak shapes when samples with high organic content are injected. Flexible systems that use custom injection programs to perform in-needle dilutions have enabled analysts to inject high organic samples, while maintaining exceptional chromatographic efficiency. As such, custom injection programs are increasingly seen as a powerful tool when it comes to rapidly transferring methods between systems.
Delivering On-Spec Data, Quickly and Efficiency, Using Intelligent Laboratory Informatics
While increased platform flexibility is streamlining method transfer workflows, other improvements in productivity are being brought about by advances in intelligent informatics and instrument design.
Among the most valuable productivity gains are those achieved by integrating HPLC instrumentation with laboratory informatics software, including chromatography data systems (CDS). By allowing analysts to set-up sequences, monitor runs and access data remotely using a CDS, these software solutions are helping teams run more samples unattended and work more efficiently to deliver high-quality results first-time around. In recent years, CDS platforms have become increasingly sophisticated, with some systems now supporting electronic workflow procedures designed for fast, error-free sequence and method set-up. Other features, such as dedicated panels for instrument control and smart tools to streamline data processing and reporting, are empowering analysts to work faster and boost productivity, while ensuring all data is managed in full compliance with regulatory requirements.
Innovative productivity tools are also being built into instruments themselves. For example, some modern HPLC platforms can monitor critical environmental parameters, such as eluent and waste solvent levels, providing automatic warnings to notify if there is insufficient eluent to complete sequences and automatically recording eluent bottle refill events in the audit trail. These simple yet effective features are designed to ensure instruments never run dry and waste will not run over, enabling laboratories to minimize the potential for human error, avoid lost time and, ultimately, run large sample sets with confidence.
Recent years have also seen the development of HPLC instruments that can monitor operational readiness through routine and automated system health checks. As a result, the early tell-tale signs of poor performance can be flagged in good time, ensuring any potential issues are resolved early, and significantly reducing unscheduled downtime or the need to re-run samples. Some of the most advanced LC instruments also incorporate intuitive diagnostic tools to quickly identify and troubleshoot issues. These systems can even display step-by-step maintenance videos on intuitive touch-screen displays, helping analysts quickly remedy issues and get workflows back online and running again faster.
Eliminating Productivity Challenges in the Pharmaceutical Sector
Productivity is a key challenge for analytical laboratories across a variety of sectors and the pharmaceutical industry is no exception. For contract development and manufacturing organizations (CDMOs), who work with a wide range of customers, diversity in analytical capability is an important consideration.
This was the situation facing a global CDMO looking to increase the flexibility and efficiency of its LC systems in order to enhance its capabilities and expand its customer base. After evaluating the available options, the company turned to the Thermo Scientific Vanquish UHPLC platform to increase its analytical capacity.
A key factor in this decision was the need for a LC platform that would simplify and accelerate method transfer workflows. Design features, such as active solvent pre-heating, were critical. This allowed the laboratory to standardize analytical performance through enhanced unit-to-unit thermal consistency, while the ability to use tool-free fluidic connections ensured full compatibility with any separation column. Other innovations, including built-in adjustable gradient delay volume control and multiple column heating modes, allowed teams to fine-tune method parameters to achieve the highest levels of reproducibility, further supporting faster method transfer.
Deployment of the new UHPLC platforms at its sites across the globe helped the organization expand its assays, such as released glycan analysis, peptide mapping and monitoring, as well as purity and ratio analysis. By increasing operational flexibility, these solutions played a critical role in boosting efficiency and productivity, while maintaining the highest standards of analytical excellence.
Conclusion
As workloads increase and businesses look to expand, analytical laboratories across multiple sectors are turning to the latest LC technologies to drive improvements in productivity. Thanks to modern LC solutions, forward-thinking laboratories are streamlining the movement of both analysts and samples to achieve substantial gains in capacity and efficiency.
Author notes: Dr. Carsten Paul is the HPLC Product Marketing Manager for Thermo Fisher Scientific's chromatography and mass spectrometry division
References:
1. Swartz, M. E.; Krull, I. Analytical Method Transfer; LCGC North America 2006, 24(11), 1204-1214, http://www.chromatographyonline.com/analytical-method-transfer-1?rel=canonical%20
2. Paul, C.; Grübner, M. et al. Thermo Scientific White Paper 72711: An instrument parameter guide for successful (U)HPLC method transfer, 2018. https://assets.thermofisher.com/TFS-Assets/CMD/Reference-Materials/wp-72711-lc-methodtransfer-guide-wp72711-en.pdf
3. Grübner, M., Paul, C., Steiner F. Thermo Scientific Application Note 72717: Method transfer of a USP derived acetaminophen assay from an Agilent 1260 Infinity system to an UltiMate 3000 SD system and a Vanquish Flex UHPLC system, 2018. https://assets.thermofisher.com/TFS-Assets/CMD/Application-Notes/an-72717-lc-method-transferusp-acetaminophen-an72717-en.pdf
4. Grosse, S.; Lovejoy, K.; De Pra, M.; Steiner, F. Improving peak results using a custom injection program to reduce solvent strength prior to sample injection, 2019. https://assets.thermofisher.com/TFS-Assets/CMD/Application-Notes/an-73186-lc-results-custom-injector-reduce-solvent-strength-an73186-en.pdf