Direct Quantitative Redox of 8 Zeptomoles of Molecules on a Macroscale Electrode

A home-built opto-electrochemical differential reflectometer, SEED, has been developed to push the measurability of electrochemical detection on macroscopic electrodes closer to its fundamental limit determined by shot noise. By positioning a redox-active dye, methylene blue (MB), close to the electrode in a DNA self-assembled monolayer (SAM), the quantitative sensitivity of SEED is measured. By performing cyclic voltammetry (CV) and SEED on more than 50 SAMs immobilized on gold electrodes without perturbing the chip, the signal of SEED at 400 V/s is shown to be linearly proportional to the local redox current measured by CV at 1 V/s. The differential reflectivity at the formal redox potential corresponding to ∼9,375 electrons was 4.5-fold above the ultimate practical shot-noise limit of counting 2,100 electrons in an electrochemical measurement, irrespective of the transduction method. The equivalent peak current of ∼0.12 pA is comparable to single-molecule electrochemistry. Combinatorial electrochemistry on a monolithic electrode is obtained by scanning the laser beam. SEED is potentially a broad platform for combinatorial electrochemistry on monolithic electrodes that, for example, can be applied to MB-tethered ssDNA SAM systems that are of pervasive interest to sense a variety of analytes, from atomic ions to biomolecules.