A substantial increase of analytical throughput in capillary electrophoresis throughput by separation-interrupted sequential injections

Abstract

How to further improve the throughput of capillary electrophoresis (CE) is a fascinating question. Herein an idea to substantially increase the throughput of CE has been proposed together with theory and experimental demonstration. The key is to introduce samples for CE, one after another, by a short suspension of voltage application, which was hence termed separation-interrupted sequential injections (Sisi). The idea was demonstrated to be feasible on a laboratory-built CE instrument coupled with tandem C⁴D (contactless capacitively-coupled conductivity) detectors. At least 50 injections of a testing sample (mixture of NH₄⁺, K⁺, Ca²⁺, Na⁺ and Mg²⁺) were successfully separated in only a single run. The separation took 145 min in total, equivalent to 2.9 min per analysis which is only 21% of that of normal CE. Quantification of the separated ions was performed, with a limit of detection of 1.1–2.6 μM, a limit of quantification of 3.2–8.9 μM, and a linear range up to 1000 μM (R² > 0.99). The recovery was between 88% and 112% measured by spiking standards into samples at low, middle and high levels. The real applicability of Sisi-CE was evaluated by direct injection and analysis of 45 mineral water samples also in a single run. Its clinical application potential was demonstrated by high throughput assay of the calcium and zinc gluconate oral solution formula, and the blood potassium of hyperkalemia and hypokalemia from patients with renal failure disease. This method can be extended to other applications such as omics studies through the use of more suitable detectors. The theory proposed may also be applicable to other high throughput methods.