In 2015, we gathered together a group of experts to ask: have we reached the limits of liquid chromatography? Our experts returned a resounding, “no!” – as they did two years later in the follow-up piece: LC on the Edge. However, ten years on – and with HPLC 2025 just around the corner – we feel the time is right to reach out to gurus old and new, take stock of the field’s progress over the past decade, and revisit our provocative question…
When you look back over the past 10 years, has HPLC innovation lived up to expectations?
The HPLC landscape over the past decade has been shaped by three core advancements, in my opinion. Firstly, UHPLC instrumentation evolved through innovations in plumbing, particularly with corrosion-resistant materials and metal-free flow paths that broadened biopharmaceutical applications. Concurrently, hyphenated techniques like LC coupled to high-resolution mass spectrometry, as well as comprehensive two-dimensional liquid chromatography (LC×LC), became indispensable for complex separations in proteomics and metabolomics – driven by the growing need for biomarker discovery and personalized medicine. Secondly, automation has been improved thanks to AI-driven software integration and optimization, reducing errors and streamlining method development. Finally, sustainability emerged as a priority, marked by eco-friendly practices, such as reduced solvent consumption, novel mobile-phase formulations, and miniaturized systems like nano-LC.
What are some of the hottest trends in HPLC today?
I agree with Fabrice (see: Meeting the Biopharmaceutical Challenge) and Gert (see: Don’t Discount Another Particle Technology Revolution) – the analysis of large biomolecules and proteomics/metabolomics approaches are certainly among the hottest trends. I would also add that many efforts are also given to the development of sustainable separation methods, for instance by designing novel adsorbents to be used in pure aqueous mobile phases or by exploring the possibility of replacing common organic modifiers with greener ones.
Is AI having an impact on the HPLC field today?
I believe that AI holds transformative potential in chromatography – to accelerate method development and enhance analytical precision, but I agree that its application is still currently limited to a research stage. Recent HPLC symposia have highlighted machine learning's ability to predict optimal chromatographic conditions, such as mobile phase composition and gradient profiles, by training algorithms on minimal experimental data, leveraging molecular properties like polarity and solubility. This approach drastically reduces the time traditionally spent on trial-and-error optimization. AI-driven tools could also address complex peak deconvolution, automating integration tasks that require manual intervention, thereby improving reproducibility and throughput.
Looking ahead, I believe that AI-powered data processing could revolutionize also the field of omics sciences by extracting functional insights from large datasets, identifying patterns (e.g., compound correlations or compositional shifts in mixtures), and enabling real-time decision-making in fields like metabolomics and proteomics. This potential could position AI as a cornerstone for next-generation chromatographic innovation.
Overall, are you optimistic about the future of HPLC?
Yes, certainly. I believe HPLC will still be considered the gold standard separation method. And given the continuous development in terms of instrumentation and column formats, I could envisage an advancement in the design of portable and miniaturized instruments for in-field analysis. This could also significantly reduce challenges in sample preparation and storage.