Please cite this article in press as: M. Gilar, et al., Chromatographic performance of microﬂuidic liquid chromatography devices: Experi- mental evaluation of straight versus serpentine packed channels, J. Chromatogr. A (2017), https://doi.org/10.1016/j.chroma.2017.12.031 ARTICLE IN PRESS G Model CHROMA-359087; No. of Pages 9 Journal of Chromatography A, xxx (2017) xxx–xxx Contents lists available at ScienceDirect Journal of Chromatography A j o ur na l ho me page: www.elsevier.com/locate/chroma Chromatographic performance of microﬂuidic liquid chromatography devices: Experimental evaluation of straight versus serpentine packed channels Martin Gilar ∗ , Thomas S. McDonald, Fabrice Gritti, Gregory T. Roman, Jay S. Johnson, Bernard Bunner, Joseph D. Michienzi, Robert A. Collamati, Jim P. Murphy, Devesh D. Satpute, Matthew P. Bannon, Dennis DellaRovere, Robert A. Jencks, Tad A. Dourdeville, Keith E. Fadgen, Geoff C. Gerhardt Waters Corporation, 34 Maple Street, Milford, MA 01757, USA a r t i c l e i n f o Article history: Received 27 October 2017 Received in revised form 6 December 2017 Accepted 12 December 2017 Available online xxx Keywords: Liquid chromatography Microﬂuidic System dispersion Peak Capacity Column efﬁciency a b s t r a c t We prepared a series of planar titanium microﬂuidic (LC) columns, each 100 mm long, with 0.15, 0.3 and 0.5 mm i.d.’s. The microﬂuidic columns were packed with 1.8 m C18 sorbent and tested under isocratic and gradient conditions. The efﬁciency and peak capacity of these devices were monitored using a micro LC instrument with minimal extra column dispersion. Columns with serpentine channels were shown to perform worse than those with straight channels. The loss of efﬁciency and peak capacity was more prominent for wider i.d. columns, presumably due to on-column band broadening imparted by the so-called “race-track” effect. The loss of chromatographic performance was partially mitigated by tapering the turns (reduction in i.d. through the curved region). While good performance was obtained for 0.15 mm i.d. devices even without turn tapering, the performance of 0.3 mm i.d. columns could be brought on par with capillary LC devices by tapering down to 2/3 of the nominal channel width in the turn regions. The loss of performance was not fully compensated for in 0.5 mm devices even when tapering was employed; 30% loss in efﬁciency and 10% loss in peak capacity was observed. The experimental data for various devices were compared using the expected theoretical relationship between peak capacity P c and efﬁciency N; (P c −1) = N 0.5 × const. While straight LC columns showed the expected behavior, the devices with serpentine channels did not adhere to the plot. The results suggest that the loss of efﬁciency due to the turns is more pronounced than the corresponding loss of peak capacity. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Microﬂuidic (LC) liquid chromatography is presently a topic of signiﬁcant research interest, particularly in ﬁelds where high- sensitivity liquid chromatography mass spectrometry (LC–MS) is employed, such as proteomics and metabolomics [1–7]. While the last two decades of research have largely focused on 75 m i.d. nano LC columns, recent enhancements in MS instrument sensi- tivity permits the use of more robust capillary and microbore LC columns (0.15–1 mm i.d.) with acceptable separation performance and MS detection limits suitable for many such applications [8–12]. ∗ Corresponding author. E-mail address: Martin Gilar@waters.com (M. Gilar). When LC is performed correctly, it offers several advantages over conventional scale LC experiments. It provides enhanced detection sensitivity (assuming that the amount of sample injected on column is not proportionally reduced), lower consumption of mobile phases, and a reduction in the negative consequences asso- ciated with the frictional heat that is generated on column during chromatography [13–16]. On the other hand, there are several challenges encountered in LC. First, due to the small peak vol- umes generated by a high efﬁciency LC separation, extra-column contributions to peak broadening have to be carefully managed to maintain acceptable separation performance [17,18]. Second, even small sample volumes (a few microliters) may exceed the volume of a LC column, creating injection related peak broaden- ing [19]. The peak broadening problem is magniﬁed in cases when the sample solvent interferes with retention (e.g. acting as strong eluent); in extreme cases peak splitting or sample breakthrough https://doi.org/10.1016/j.chroma.2017.12.031 0021-9673/© 2017 Elsevier B.V. All rights reserved.