Computational Fluid Dynamics Study of the Dispersion Caused by Capillary Misconnection in Nano-Flow Liquid Chromatography.

It is well known that high-speed/high-efficiency separations in nano-flow liquid chromatography (LC) are very sensitive to the quality of the connections between the column and the rest of the instrument. In the present study, two types of connection errors (capillary misalignment and the occurrence of an inter-capillary gap) have been investigated using computational fluid dynamics. Interestingly, it has been found that large degrees of capillary misalignment (assuming an otherwise perfect contact between the capillary end-faces) can be afforded without introducing any significant dispersion over the entire range of investigated relative misalignment errors (0 ≤ ε/dcap ≤ 75%), even at the largest flow rates considered in nano-LC. On the other hand, when an inter-capillary gap is present, the dispersion very rapidly increases with the radial width Dc of this gap (extra variance ∼Dcn with n even reaching values above 4). The dependency on the gap length Lc is however much smaller. Results show that, when Dc ≤ 30 µm and Lc ≤ 200 µm, dispersion losses can be limited to the order of 1 nL2 at a flow of 1.5 µL/min, which is generally very small compared to the dispersion in the capillaries (20 µm i.d.) themselves. This result also reconfirms that zero-dead volume connectors with a sufficiently narrow bore can in theory be used without compromising peak dispersion in nano-LC, at least when the capillaries can be matched perfectly to the connector in- and outlet faces. The results are also indicative of the extra dispersion occurring inside microfluidic chips or in the connections between a microfluidic chip and the outer world.