Enhancing the Sensitivity of Photoelectrochemical DNA Biosensing Using Plasmonic DNA Barcodes and Differential Signal Readout

Abstract

Photoelectrochemical biosensors hold great promise for sensitive bioanalysis; however, similar to their electrochemical analogues, they are highly affected by the variable backgrounds caused by biological matrices. We developed a new PEC biosensing strategy that uses differential signal generation, combining signals from two separate but correlated binding events on the biosensor, for improving the limit‐of‐detection, sensitivity, and specificity of PEC DNA biosensors in biological samples. In this assay, the binding of unlabeled target DNA is followed by the capture of a signal amplification barcode featuring a plasmonic nanoparticle. The interaction of the plasmonic barcode with the semiconductive building blocks of the biosensor results in significant signal amplification, and together with differential signal processing enhances the limit of detection and sensitivity of the assay by up to 15‐ and three‐fold, respectively, compared to the previously‐used PEC assays with a single binding event, demonstrating a limit of detection of 3 fM.

Development of Nucleic‐Acid‐Based Electrochemical Biosensors for Clinical Applications

“…Synthetic DNA molecules have also been exploited as reporting probes (Figure 2B) because they can be easily modified with both biorecognition elements (such as antibodies) and reporter labels (such as redox molecules, fluorophores, or Raman probes) [68] . Additionally, inherent properties of nucleic acids, such as steric hindrance [69] and electrostatic repulsion on a surface (Figure 2B i), [70] molecular dynamics on a surface (Figure 2B ii), [71] and target‐induced strand displacement (Figure 2B iii), [72, 73] are strategically used to build molecular systems that translate target binding to a detectible signal. Such systems have been used in recent years to streamline antibody‐based assays for use in clinical and wearable settings [34, 71, 74–76] …”

Square wave voltammetry enables measurement of light-activated oxidations and reductions on n-type semiconductor/metal junction light-addressable electrochemical sensors

“…While other methods exist, 2,[28][29][30][31][32][33][34][35][36][37][38] an appealing sensor configuration for LAES is to use a semiconductor/metal (SM) or semiconductor/insulator/metal (MIS) junction. In an idealized SM junction LAES, the semiconductor serves as the light absorber while the metal layer serves as the interface for electron transfer with the solution (i.e., the sensing layer).…”

Recent advances in electron manipulation of nanomaterials for photoelectrochemical biosensors

“…Photoelectrochemical (PEC) biosensing is a promising and rapidly growing bioanalytical technique. [1][2][3][4][5] PEC biosensors work on the principle of a light excitation-dependent electrochemical process known as the PEC process. 6 To be more specific, it refers to the process in which molecules, ions or semiconductors absorb photons under light irradiation and generate excited electrons to accomplish charge transfer, thus realizing photoelectric (PE) conversion.…”