High Throughput Microflow LC/MS: Sensitivity Gains On a Practical Timescale

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Michael Donegan, James Murphy, Angela Doneanu
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Microflow LC/MS has been shown to offer significant sensitivity gains over traditional 2.1 x 50 mm UPLC approaches.1 The reason for the observed signal gains in microflow lies in the fact that lower flow rates improve the sampling efficiency of the electrospray plume and generate a finer and less disperse spray. Also, as the column diameter decreases, analytes elute off of the LC column with a much lower volume and result in peaks with a higher signal-to-noise (S/N) ratio as compared to its UPLC counterpart. Sensitivity gains are always welcome in an ever-changing landscape where bioanalytical demands are being escalated every day. However, one of the downsides of using a microfluidic approach is that lower flow rates can also translate into longer run times.

From a practical perspective, longer run times mean longer turnaround times for results. For time sensitive studies, delays in reporting data can impact research decisions upstream. The effect would also be felt by contract research organizations that charge per sample. Longer run times result in less profit per instrument. Run times are more than just actual hours. Sample thaw time and re-prep time also factor into analysis time. A typical pharmacokinetic study with 3 animals dosed intravenous (i.v.) and 3 animals dosed orally (p.o) will consist of approximately 66 samples. If blanks and standards are included, the number of injections increases to approximately 110 for the entire study. A typical microflow LC/MS run at 12 minutes per injection would take 1320 minutes or 22 hours to complete. The same study at 3 minutes per injection would only take 5.5 hours. The entire study could be completed in a single 8-hour work day and, additionally, three other studies could be conducted in the evening and overnight.

In this presentation, we will introduce a novel microfluidic device capable of higher pressures and flow rates which enable run times under 3 minutes while still delivering improved sensitivity over traditional UPLC systems.

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