The Next Big (or Small) Thing
The huge diversity of applications – old, new, and emerging – that must be addressed by modern liquid chromatography presents challenges and opportunities. In this double-barreled feature, we attempt to predict LC’s way forward in our leaders’ “wish list” – and profile advances in one important direction: portability.
Emily Hilder, Pat Sandra, Janusz Pawliszyn, Ian Wilson, Steven Lehotay, Susan Olesik, Sebastiaan Eeltink, Michal Holcapek, Kevin Schug, Hans-Gerd Janssen, Frantisek Svec, Lourdes Ramos |
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:
- An expert system that suggests the right column and mobile phase once you enter the structures you want to separate,
- Routine LC in less than 10s,
- 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:
- 2D and 3D HPLC separation methods with a total peak capacity that can reproducibly separate thousands of compounds.
- Preconcentration methods that can concentrate compounds based on compound class.
- Column technology that is even more efficient than existing sub 2-micron particle technology.
- 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.