Scanning Local Redox on 10 Micron Spots on a Monolith Electrode to Quantify Multiple Analytes at 10 Attomolar Sensitivity with Dynamic Range of Seven Orders of Magnitude

Abstract

Electrochemical transduction is arguably the most prolific and impactful method to sense chemicals and biochemicals. For example, electrochemical methods have the distinct advantage to quantitatively measure nucleic acid (NA) sequences at a limit of quantification (LOQ) of 10 attomolars and high sequence specificity. The sensitivity and dynamic range significantly surpasses optical/spectroscopic, gravimetric, and electronic transduction methods. However, electrochemical sensing cannot be easily multiplexed. Only one analyte per electrode can be measured. Furthermore, the electrode size, i.e., the sensor area, for reasonable redox current, is typically, at least 1 mm2 for small analyte concentration.A fully automated instrument, called the Scanning Electrometer for Electrical Double-layer (SEED), will be described that addresses the abovementioned limitations. SEED, based on differential optics, quantitatively measures electrochemical process by changes in the electrical double-layer (EDL) and the surface during electrochemical process. The instrument can be operated in three modes: (a) reflectivity; (b) interferometry; (c) spectroscopy. The instrument can be toggled between the three modes without moving the sample or realigning the optics. The three modes measure the structural change at the surface, change in charge state of the EDL, and change in the molecule’s electronic structure due to the electrochemical process.The principle will be described with following applications in material science, sensing and life science: (i) miRNA profiling at LOQ of 10 attomolar with dynamic range of seven orders of magnitude; (ii) single base mutation in NA sequence; (iii) heavy metal ion detection from ppt to ppb levels; (iv) spectroscopic measurement during redox on graphene; (v) Langmuir adsorption of ions on Au electrode; and (vi) direct measurement of potential of zero charge (PZC). Figure 1