Ultrasensitive Cross-Correlation Electrophoresis on Microchip Devices

Cross-correlation electrophoresis with fluorescence detection on a microchip device was used to resolve a mixture of 63 pM fluorescein and 70 pM dichlorofluorescein. The signal-to-noise ratios of analyte peaks in a correlogram derived from a 9-bit pseudorandom injection sequence were ∼17 for dichlorofluorescein and ∼6 for fluorescein. In contrast, neither peak was detected in a conventional electropherogram obtained on the microchip. Detection limits estimated from a correlogram derived from the average of 12 7-bit correlograms were 6.5 pM dichlorofluorescein and 21 pM fluorescein. These are the lowest detection limits reported for a microchip separation device using analog detection and the first example of cross-correlation electrophoresis on a monolithic device. The small injection volumes, injection reproducibility, and rapid separations enabled by microchip devices make cross-correlation multiplex injection schemes a viable approach for achieving enhanced sensitivity.