Improving chip-to-chip precision in disposable microchip capillary electrophoresis devices with internal standards

To realize portable systems for routine measurements in point-of-care settings, MCE methods are required to be robust across many single-use chips. While it is well-known internal standards (ISTDs) improve run-to-run precision, a systematic investigation is necessary to determine the significance of chip-to-chip imprecision in MCE and how ISTDs account for it. This paper addresses this question by exploring the reproducibility of Na quantification across six basic, in-house fabricated microchips. A dataset of 900 electrophoerograms was collected from analyzing five concentrations of NaCl with two ISTDs (CsCl and LiCl). While both improved the peak area reproducibility, the Na/Cs ratio was superior to the Na/Li ratio (improving the RSD by a factor of 2-4, depending on the Na concentration). We attribute this to the significant variation in microchannel surface properties, which was accounted for by cesium but not lithium. Microchip dimension and detector variations were only a few percent, and could be improved through commercial fabrication over in-house made microchips. These results demonstrate that ISTDs not only correct for intrachip imprecision, but are also a viable means to correct for chip-to-chip imprecision inherent in disposable, point-of-care MCE devices. However, as expected, the internal standard must be carefully chosen.