Label-free specific detection of femtomolar cardiac troponin using an integrated nanoslit array fluidic diode.

Abstract

We demonstrate here for the first time the utility of an integrated nanofluidic diode for detecting and quantifying physiologically relevant macromolecules. Troponin T, a key human cardiac protein biomarker, was selectively and rapidly detected free of labels for concentrations down to 10 fg/mL (∼ 0.3 fM) in buffer as well as 10 pg/mL (∼ 300 fM) in untreated human serum. This ultrasensitive detection arises from monolithic integration of a unique nanofluidic diode structure that is highly robust and amenable to site-specific surface modification. The structure features a planar nanoslit array where each nanoslit is defined at a nominal width of 70 nm over a micrometer-scale silicon trench without the use of high-resolution patterning techniques. Through vapor deposition, a glass layer is placed at a nonuniform thickness, tapering the trench profile upward and contributing to the triangular nanoslit structure. This asymmetric profile is essential for ionic current rectification noted here at various pH values, ionic strengths, and captured target species, which modulate the surface-charge density within the sensitive region of the nanoslit. The nanoslit, unlike nanopores, offers only 1D confinement, which appears to be adequate for reasonable rectification. The measurements are found in quantitative agreement with the diode simulations for the first time based on a pH- and salt-dependent surface-charge model.