Introducing Nanoscale Electrochemistry in Small-Molecule Detection for Tackling Existing Limitations of Affinity-Based Label-Free Biosensing Applications.

Electrochemical sensing techniques for small molecules have progressed in many applications, including disease diagnosis and prevention as well as monitoring of health conditions. However, affinity-based detection for low-abundance small molecules is still challenging due to the imbalance in target-to-receptor size ratio as well as the lack of a highly sensitive signal transducing method. Herein, we introduced nanoscale electrochemistry in affinity-based small molecule detection by measuring the change of quantum electrochemical properties with a nanoscale artificial receptor upon binding. We prepared a nanoscale molecularly imprinted composite polymer (MICP) for cortisol by electrochemically copolymerizing ß-cyclodextrin and redox-active methylene blue to offer a high target-to-receptor size ratio, thus realizing "bind-and-read" detection of cortisol as a representative target small molecule, along with extremely high sensitivity. Using the quantum conductance measurement, the present MICP-based sensor can detect cortisol from 1.00 × 10-12 to 1.00 × 10-6 M with a detection limit of 3.93 × 10-13 M (S/N = 3), which is much lower than those obtained with other electrochemical methods. Moreover, the present MICP-based cortisol sensor exhibited reversible cortisol sensing capability through a simple electrochemical regeneration process without cumbersome steps of washing and solution change, which enables "continuous detection". In situ detection of cortisol in human saliva following circadian rhythm was carried out with the present MICP-based cortisol sensor, and the results were validated with the LC-MS/MS method. Consequently, this present cortisol sensor based on nanoscale MICP and quantum electrochemistry overcomes the limitations of affinity-based biosensors, opening up new possibilities for sensor applications in point-of-care and wearable healthcare devices.

One-Step Fabrication of Highly Sensitive Tris(2,2'-bipyridyl)ruthenium(II) Electrogenerated Chemiluminescence Sensor Based on Graphene-Titania-Nafion Composite Film.

A highly sensitive tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)32+) electrogenerated chemiluminescence (ECL) sensor based on a graphene-titania-Nafion composite film has been prepared in a simple one-step manner. In the present work, a highly concentrated 0.1 M Ru(bpy)32+ solution was mixed with an as-prepared graphene-titania-Nafion composite solution (1:20, v/v), and then a small aliquot (2 µL) of the resulting mixture solution was cast on a glassy carbon electrode surface. This one-step process for the construction of an ECL sensor shortens the fabrication time and leads to reproducible ECL signals. Due to the synergistic effect of conductive graphene and mesoporous sol-gel derived titania-Nafion composite, the present ECL sensor leads to a highly sensitive detection of tripropylamine from 1.0 × 10-8 M to 2.0 × 10-3 M with a detection limit of 0.8 nM (S/N = 3), which is lower in comparison to that of the ECL sensor based on the corresponding ECL sensor based on the titania-Nafion composite containing carbon nanotube. The present ECL sensor also shows a good response for nicotinamide adenine dinucleotide hydrogen (NADH) from 1.0 × 10-6 M to 1.0 × 10-3 M with a detection limit of 0.4 µM (S/N = 3). Thus, the present ECL sensor can offer potential benefits in the development of dehydrogenase-based biosensors.