Field-effect based attomole titrations in nanoconfinement

This paper describes a novel capacitive method to change the pH in micro- and nanofluidic channels. A device with two metal gate electrodes outside an insulating channel wall is used for this purpose. The device is operated at high ionic strength with thin double layers. We demonstrate that gate potentials applied between the electrodes cause a release or uptake of protons from the silicon nitride surface groups, resulting in a pH shift in the channel and a titration of solution compounds present. Due to the high quality silicon nitride insulating layer, the effect is purely capacitive and electrolysis can be neglected. Fluorescein was employed as a fluorescent pH indicator to quantify the induced pH changes, and a maximum change of 1.6 pH units was calculated. A linear relationship was found between applied potential and fluorescein intensity change, indicating a linear relation between actuated proton amount and applied voltage. Since this pH actuation method avoids redox reactions and can be operated at physiological ionic strength, it can be very useful as a "soft" way to change the pH in very small volumes e.g. in bioassays or cell-based research. The sensitivity of the optical detection method poses the only limit to the detectable amount of substance and the observed volume. In a preliminary measurement we show one possible application, namely titration of 100 attomol of TRIS in a 7 pL detection volume. It is important to stress that this pH actuation principle fundamentally differs from the pH changes occurring in ionic transistors which are due to counterion enrichment and coion exclusion, because it does not rely on double-layer overlap. As a result it can be operated at high ionic strength and in channels of up to at least 1 microm height.