Miniaturization in LC – MS

2 Introduction In the April edition of this magazine1 Ron Majors, in his annual report on new columns and accessories from the Pittsburgh conference, reported how at the 2002 conference the largest number of product introductions were for biomolecule separations and for liquid chromatography–mass spectrometry (LC–MS). He went on to state that speciality HPLC columns for chiral compounds, biomolecules, combinational chemistry, carbohydrate analysis and LC–MS represented the largest category of entries. Supporting these products was an increase in capillary and nano-LC columns for LC–MS. But more important the support accessories (e.g., mixers, valves and connecting tubes) were also shown for the new capillary columns. Our immediate response was to say “about time”; at last we are starting to realize the advantages of moving to capillary systems and at last instrument and column manufacturers are starting to introduce the products. We have read and understood many articles over the last 35 years talking about the advantages of capillary columns; this includes the first paper we are aware of in microcolumn LC by Horvath2 who used 0.5–1.0 mm i.d. stainless steel columns packed with large pellicular materials (15 μm) for the separation of ribonucleotides. This like many other classic papers was ignored until the mid 1970s when Ishii demonstrated the use of slurry-packed PTFE columns.3 This work was performed with 1.0 mm i.d. columns, which in the late 1970s was really pushing the instrumentation boundaries, particularly for pumps, micro-injectors and, especially, detectors. From these developments we then saw the classic work that really laid down the foundations of the miniaturization of LC columns by Novonty.4 But here we are in the 21st century and we are only just starting to see the expansion of capillary and maybe nanocolumns into the laboratory and out of the hands of researchers. Why is this so when all the work of Novonty and others has shown so many advantages in terms of sample size, small volumetric flow-rates, and the enhanced detection performance that can be obtained by using concentration-sensitive detection devices.5 The answer must lie in the old “Catch 22” circular argument of needs versus instrumentation versus new applications versus existing applications and that it is only now with the new breed of mass spectrometer and the new requirements in the fields of genomics that manufacturers are developing the instrumentation for miniaturization in LC columns.