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Techniques & Tools Liquid Chromatography

The Next Big (or Small) Thing

The Wish List: Liquid Chromatography

In this issue, we’re exploring a host of exciting advances in separation science – from miniaturized HPLC systems (here) to the evolution of sample preparation (here). But what’s the next big priority for LC development? We asked leading chromatographers what advances they would most like to see and why. Here’s what they told us…

“I’d like to see the development of columns covering all LC modes with internal diameters (ID) of 1 mm, packed with particles (porous or superficially porous) and offering, with high reproducibility, the same efficiency as columns of 3 to 4.6 mm ID. To make this wish possible, we need instrumentation that provides dead volumes able to cope with such small IDs. Not only do we need optimal mobile phase flows in the order of 50 µL/min (20 times lower compared with the 1 mL/min for 4.6 mm ID columns) for R&D purposes, but there is also no fundamental reason not to implement such columns in QA/QC (green chemistry!).”

Pat Sandra, Emeritus Professor, Organic Chemistry, Ghent University; Founder and President, Research Institute for Chromatography, Kortrijk, Belgium.

“A great deal of research is focused on improving efficiency of separation. The other important practical aspect of SPME application would be to improve background and carry-over issues, which would require understanding the sources of column contamination, as well as improvements in the design of LC components to minimize carry-over. Longer term, I’d like to see improved fundamentals and instrumentation to facilitate on-line multi-dimensional separations, including heart cutting. The miniaturization of LC systems and use of alternative pumping systems, such as electro-osmotic pumping, are also important future directions.”

Janusz Pawliszyn, Professor, Department of Chemistry, University of Waterloo, Ontario, Canada.

“I would like to have a single, robust, high-resolution (UHPLC or better) universal stationary phase capable of resolving the whole spectrum of low molecular mass metabolites/small peptides (from polar ionic, polar-neutral, through mid-polar, all the way up to non-polar lipids) in a single LC-MS compatible separation, to be able to rapidly and reproducibly metabolically phenotype biological samples for metabolomics/metabonomics applications.”

Ian Wilson, Professor, Chair in Drug Metabolism and Molecular Toxicology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, UK.

“Stationary phases allowing for an even better retention and separation of compounds, exhibiting an extensive spectrum of polarities, would be particularly desirable. Especially in light of the growing relevance of multi-analyte test methods, employing targeted as well as non-targeted approaches, we need the highest performance in LC systems.”

Anonymous (working in forensics)

“During my 30 years in chromatography, I have been amazed by the technical improvements in (U)HPLC, but I get sticker shock at the costs and miss the ability to use modular LC components with any detector from any vendor. So my wish is for better modularity and interchangeability between vendor LC and detection systems.”

Steven Lehotay, Lead Scientist, USDA Agricultural Research Service, Eastern Regional Research Center, Pennsylvania, USA.

“I would like:

  1. An expert system that suggests the right column and mobile phase once you enter the structures you want to separate,
  2. Routine LC in less than 10s,
  3. Lipid isomer columns.”

Bob Kennedy, Hobart H Willard Distinguished University Professor of Chemistry; Professor of Chemistry, Chair-Chemistry, College of LS&A; Professor of Pharmacology, Medical School, University of Michigan, Ann Arbor, USA.

“A transfer interface/strategy that makes fully uncoupled operation between the two separation processes in LC×LC possible, while still allowing complete and focused transfer of the eluent from the first dimension to the second, providing a flexible, universal and easy to optimize analytical platform.”

Lourdes Ramos, Research Scientist, Department of Instrumental Analysis and Environmental Chemistry, Institute of Organic Chemistry, Scientific Research Council (CSIC), Madrid, Spain.

“This Christmas, I wish Santa would bring me a really sensitive on-column UV absorbance detector with a physical diametric path length of 25 microns or smaller.”

Sandy Dasgupta, Hamish Small Chair in Ion Analysis, Department of Chemistry and Biochemistry, University of Texas at Arlington, Texas, USA.

“Separations providing increased peak capacities and peak generation rates (essentially more resolution, and faster!), so as to enable analyses that provide increased dynamic range and speed for applications involving highly complex samples in conjunction with mass spectrometry, such as those in proteomics and metabolomics.”

Dick Smith, Battelle Fellow and Chief Scientist, Biological Sciences Division, Pacific Northwest National Laboratory (PNNL), Washington, USA.

“LC separation of a wide range of polar and non-polar compounds in water would be nice.”

Xing-Fang Li, Professor, Division of Analytical and Environmental Toxicology, University of Alberta, Alberta, Canada.

“I would most like to see highly efficient 3D printed columns. These computer-designed columns need to be identical, so we need suitable materials to create both the column and the filling at the same time, and high-speed high-resolution printers. By default, the filling must be a monolith.”

Frantisek Svec, Facility Director, Organic and Macromolecular Synthesis, Lawrence Berkeley National Laboratory, Berkeley, USA.

“A universal LC-MS interface that allows the ionization of all compounds irrespective of their polarity, size, volatility and so on; plus, gives a more or less constant response for all species – so that universal calibration factors can be employed and compounds for which no standards are available can be quantified.”

Hans-Gerd Janssen, Science Leader Analytical Chemistry, Unilever Research Vlaardingen, and Professor of Biomacromolecular Separations, van’t Hoff Institute for Molecular Sciences, University of Amsterdam, the Netherlands.

“The desire for intact protein analysis has grown tremendously. We need more and new liquid chromatography stationary phase/support combinations and concepts to provide a wider range of selectivity for intact protein separations. Ideal products would be able to work over a wider pH range (especially above pH 8), have potential to recognize variable and changing protein conformations, and be extremely robust.”

Kevin Schug, Shimadzu Distinguished Professor of Analytical Chemistry, University of Texas at Arlington, Texas, USA. 

“My coworkers and I would appreciate having 1 mm columns with various chemistries and robust long-term performance at ultrahigh pressures, providing ultrafast separations easily interfaced with mass spectrometry. Such columns would use optimal flow rates for maximum sensitivity with electrospray, but would  still be robust enough for high-throughput LC-MS quantitation.”

Michal Holčapek, Professor, Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Czech Republic.

“My long-term wish is the development of comprehensive spatial 3D-LC chip technology, overcoming classical sequential analysis of fractions that incorporate novel flow control mechanisms between different developments. This technology has the potential to achieve truly high peak capacities in the minimum amount of time (compared to classical 2D-LC technology).”

Sebastiaan Eeltink, Department of Chemical Engineering, Vrije Universiteit Brussel, Brussels, Belgium.

“My wish list would include:

  1. 2D and 3D HPLC separation methods with a total peak capacity that can reproducibly separate thousands of compounds.
  2. Preconcentration methods that can concentrate compounds based on compound class.
  3. Column technology that is even more efficient than existing sub 2-micron particle technology.
  4. Columns and preconcentration devices that can improve the dynamic range of analyses.”

Susan Olesik, Dow Professor and Chair, Department of Chemistry and Biochemistry, The Ohio State University, USA.

“My big LC wish is for hardware that allows us to achieve the full potential of fast separations and miniaturization. For example, can we re-engineer how we introduce the sample (the injector) and the detector to take advantage of these performance gains?”

Emily Hilder, Director: Future Industries Institute, University of South Australia, Australia.

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About the Authors
Emily Hilder

Emily Hilder is Professor and ARC Future Fellow in the Australian Centre for Research on Separation Science (ACROSS) and School of Chemistry at the University of Tasmania. Her research focuses on the design and application of new polymeric materials, in particular polymer monoliths, in all areas of separation science. She is also interested in the development of miniaturised analytical systems, particularly for applications in clinical diagnostics and remote monitoring. She has over 95 peer-reviewed publications and was recently recognised as the LCGC Emerging Leader in Chromatography (2012). She is also an Editor of the Journal of Separation Science.

Pat Sandra

Pat Sandra is Emeritus Professor of Organic Chemistry at Ghent University, and Founder and President of the Research Institute for Chromatography (RIC), Kortrijk, Belgium. “Through the activities of RIC, I got in touch with the real analytical needs of the industry and found we could help in providing solutions that are economically relevant. Moreover, it allowed me to keep my best PhD students around me, which resulted in high scientific output in a non-academic environment,” he says.

Janusz Pawliszyn

Janusz Pawliszyn is Professor at the Department of Chemistry, University of Waterloo, Ontario, Canada.

Ian Wilson

Ian Wilson is Chair in Drug Metabolism and Molecular Toxicology, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London, UK.

For his PhD, Ian Wilson used GC to analyze steroid hormones in insects. Much of his subsequent career has been in the pharmaceutical industry, working in discovery and development. In 2012, Ian moved to Imperial College, London. His research interests include separations science, particularly the development of hyphenated techniques in chromatography, and spectroscopy, and the application of these techniques to problems in drug metabolism and metabonomics. When not working on these topics he collects old instruments and has a large collection of old gas and liquid chromatographs.

Steven Lehotay

Steve is a Lead Scientist with the USDA Agricultural Research Service, Eastern Regional Research Center in Wyndmoor, Pennsylvania, USA.

Susan Olesik

Dow Professor and Chair at The Ohio State University, USA, explains why time and effort spent inspiring young minds is an investment in the secure future of science, technology, engineering and mathematics (STEM) fields.

Sebastiaan Eeltink
Sebastiaan Eeltink

Sebastiaan Eeltink received his PhD degree in chemistry (specializing in analytical chemistry) in 2005 from the University of Amsterdam. Thereafter, he conducted postdoctoral research at the University of California, Berkeley, USA, and was guest scientist at the Lawrence Berkeley National Laboratory. In 2007, he joined Dionex and conducted research on packed and monolith column technology for ultra-high-pressure LC, twodimensional LC, and nanoLC. Eeltink is now research professor at the Department of Chemical Engineering at the Free University of Brussels, where he focuses on the development, characterization, and application of novel chromatography materials, including nano-structured monolithic materials and coatings in capillaries and micro-fluidic devices, for ultra-high-pressure and multidimensional (spatial) LC-MS separations.

Michal Holcapek

Kevin Schug

Kevin Schug is Shimadzu Distinguished Professor of Analytical Chemistry, University of Texas Arlington, USA.

Hans-Gerd Janssen

Hans-Gerd Janssen is Science Leader of Analytical Chemistry at Unilever Research Vlaardingen, and Professor of Biomacromolecular Separations at the van’t Hoff Institute for Molecular Sciences at the University of Amsterdam, the Netherlands.


Frantisek Svec

Frantisek Svec lives in California and is Professor at the Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, China and at the Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic. He received a BSc in chemistry and PhD in polymer chemistry from the Institute of Chemical Technology, Prague (Czech Republic). In 1976 he joined the Institute of Macromolecular Chemistry of the Czechoslovak Academy of Sciences, before joining the faculty at Cornell University in 1992. In 1997, he was appointed at the University of California, Berkeley and also affiliated with the Molecular Foundry of the Lawrence Berkeley National Laboratory. Svec has authored 450 scientific publications, edited two books, and authored 75 patents. He is editor-in-chief of the Journal of Separation Science, member of editorial boards of a number of renowned journals and was President of CASSS in 2003–2015. He is best known for his research in the area of monoliths and their use in liquid chromatography, electrochromatography, supports for solid phase chemistry, enzyme immobilization, and microfluidics.

Lourdes Ramos

Lourdes Ramos is a research scientist at the Department of Instrumental Analysis and Environmental Chemistry, in the Institute of Organic Chemistry (CSIC, Madrid, Spain). Her research activities include the development of new miniaturized sample preparation methods for the fast determination of organic microcontaminants in environmental and food samples, as well as the evaluation of new chromatographic techniques – especially GC×GC based approaches – for unravelling the composition of complex mixtures.

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