Neglected Micro LC

It’s clear that good ideas do not always end up in the form of real applications – indeed, this is often true whenever a ‘new’ technology emerges. One good example (or bad example, depending on your perspective) is supercritical fluid chromatography (SFC), which – after its glorious future had been predicted – fell into oblivion for quite some time. The same demise was suffered by micro liquid chromatography, which was identified early on as a key technology to reduce toxic organic solvents while speeding up the separation process.

It’s reasonable to question why this happened. But the answer, when you think about it, is reasonably simple: the technological aspects of micro-LC were poorly developed back then, and high-efficiency separation media were not commercially available. With the introduction of modern UHPLC instruments in around 2004, column technology also took a giant step forward; after all, sub-2-micron particles are key to improving the efficiency of small i.d. columns. Nevertheless, there are still some strong prejudices against micro-LC that center around the robustness of the technology, which is claimed to be very poor. Moreover, the common opinion remains that micro-LC columns cannot be packed very efficiently. And yet, if we look to the scientific literature, the available data is not able to fully support the thesis or antithesis of this statement. To that end, a much wider base of research is needed to prove (or disprove) the hypotheses. Either way, column manufacturers will need to focus on developing more reliable packing protocols for small-scale columns. Unfortunately, if the demand is low, then the incentive to do so is also low.

Another micro-LC myth is that dedicated instrumentation is not commercially available. Clearly, that is not true. I can only assume that several small- and medium-sized companies with excellent products in their portfolio have been overlooked. In fact, microfluidic flow control has been commercially available for at least ten years, and such platforms have extremely low system volumes.

A further advantage of micro-LC is that hyphenation with mass spectrometry can be very easy. Some manufacturers offer the possibility to simply replace the emitter tip within the ion source, meaning that no further adjustments on the hardware are necessary if you wish to access micro-LC. And if MS detection is unnecessary or unwanted, UV- and fluorescence type detectors with extremely low cell volumes (just a few nanoliters) are also commercially available.

So in fact, it seems that the technology is in place, which means that the biggest hurdle to overcome is an area that we can address immediately: education. Here, academic institutions and universities should grasp hold of their responsibility by using state-of-the art technology rather than old-fashioned equipment. I’m really flabbergasted when I think about the technological advances in telecommunications over the last ten years. Today, we all manage our lives with smart mobile phones – all despite tremendous security issues that still have to be resolved. In stark contrast, the ‘modern’ laboratory sometimes reminds me of some relic from a bygone era – where the introduction of modern technology is still hampered by the opinion that the re-validation of methods renders the transfer over to improved techniques or systems impossible. If this is the common opinion, then why should there be any need to invest in modern technology at all?