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August/September 2011
by microfluidics, this scale lacks the robustness most LC users are accustomed to.
Figure 5: TRIZAIC UPLC source for Waters Xevo and Synapt mass spectrometers.
a significant improvement in usability became our initial goal. We focused on the development of an integrated cartridge, what became the TRIZAIC UPLC nanoTile, that could be inserted into a clamp assembly. After inserting the nanoTile into the clamp assembly and rotating a lever 80o
While we initially focused on proteomics applications and nano-scale LC, the microfluidic platforms we have been developing are capable of going to higher pressures, and larger channel diameters. Moving up to the 150-300 µm scale, flow rates get quite a bit faster (2 to15 µL/min). At these flow rates the benefits become become obvious: a typical LC system performs faster, electrospray performance is more robust and requires less tuning and larger sample volumes can be introduced.
this clamp
assembly makes all the connections into the nanoTile: high pressure fluidic fittings, low voltage connections for a heater, temperature sensor, an EPROM for storing data, an electrospray tip as well as gas connections for the nebulisation gas. It was a big challenge to integrate all those features onto a single, integrated device and maintain UPLC performance.
Where do you see this ‘chip based technology’ in 5 years time? Has the technology reached a plateau, maybe waiting for other components within an Instrument to be able to realise the improvements in instrument design?
As I mentioned earlier, the primary rationale for Waters developing a microfluidic LC system has been to improve usability, while maintaining UPLC performance. Currently, the primary users for nano-scale microfluidic LC are doing discovery proteomics, and are sample limited. While there are real sensitivity benefits to working at the nano scale, even with improvements brought on
So, while microfluidic LC has primarily been used for proteomics up until now, over the next five years, I think we will see implementation of capillary-scale microfluidic systems that will attract LC users who typically work at the analytical scale. I expect that we will push the performance of separations on a microscale past that of analytical scale. With analytical scale LC we are currently using 1.7 micron particles at 15,000 PSI. Benefits of reduced solvent consumption, higher sensitivities will be realised with the same or better robustness as analytical scale.
For all of the advantages (perceived and realised) that chip based technology brings to the industry are there any application areas, e.g. small molecule, proteomics, environmental which could directly benefit from the technology?
As I mentioned, we have been developing microfluidic platforms that will allow us to expand microfluidic LC beyond typical nano- scale applications into applications traditionally performed at the analytical scale.
Examples are microsampling for bioanalysis and dried blood spot analysis where you are no longer using a test tube of blood to draw a sample, but where the sample is drawn from a few microlitres of blood spotted onto
a piece of paper. These small sample volume applications require higher sensitivity, and with a microfluidic format, we can provide these sensitivity improvements while maintaining the robustness and ease-of-use of an analytical-scale LC system.
Aside from the performance benefits that can be achieved with microfluidic LC, using microfluidic LC can also improve the usability of LC/MS systems. We see that most scientists view LC as a tool, and as such, it should be easier to use and easier to train people on. If cartridge-like consumables can be integrated into more LC/MS systems, researchers can spend more time acquiring data than setting up the instrumentation. When I was a practicing analytical chemist in the 1990’s at the Canadian Food Inspection Agency, the lab I was part of was responsible for monitoring Canada’s meat for drug residues. Typically, we used LC/UV systems for screening, and then if we got a positive result, that sample would be taken to the mass spectrometry technician to run a confirmatory analysis.
Those days are over. The lab I used to work in now has LC/MS systems for every chemist. That’s because the technology had become so robust and easy enough to use that mass spectrometry specialists are no longer needed to run samples.
Further improvements in usability and integration can be achieved with microfluidics that will allow LC/MS technology to extend beyond the analytical lab. Right now, we are being asked to create “Open Access” systems where anyone can walk up and load samples for analysis. The ultimate goal for any analytical technology is to allow it to be viewed as simple analyser that can deliver an answer. While we are a long way from creating an LC/MS “analyser” that can be used by an untrained user, this is the ultimate goal, and I think microfluidic technology will play an important role in realising this.
(1) A. Manz*, , J.C. Fettinger, E. Verpoorte, H. Lüdi, H.M. Widmer and D.J. Harrison Trends in Analytical Chemistry 1991, Micro machining of monocrystalline silicon and glass for chemical analysis systems. A look into next century's technology or just a fashionable craze?
Figure 4: TRIZAIC UPLC nanoTile encases everything needed for nanoUPLC separations.
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