Integrated internal standards: A sample prep-free method for better precision in microchip CE

Point-of-care systems based on microchip capillary electrophoresis require single-use, disposable microchips prefilled with all necessary solutions so an untrained operator only needs to apply the sample and perform the analysis. While microchip fabrication can be (and has been) standardized, some manufacturing differences between microchips are unavoidable. To improve analyte precision without increasing device costs or introducing additional error sources, we recently proposed the use of integrated internal standards (ISTDs): ions added to the BGE in small concentrations which form system peaks in the electropherogram that can be used as a measurement reference. Here, we further expand this initial proof-of-principle test to study a clinically-relevant application of K ion concentrations in human blood; however, using a mock blood solution instead of real samples to avoid interference from other obstacles (e.g. cell lysis). Cs as an integrated ISTD improves repeatability of K ion migration times from 6.97% to 0.89% and the linear calibration correlation coefficient (R ² ) for K quantification from 0.851 to 0.967. Peak area repeatability improves from 11.6–13.3% to 4.75–5.04% at each K concentration above the LOQ. These results further validate the feasibility of using integrated ISTDs to improve imprecision in disposable microchip CE devices by demonstrating their application for physiological samples.