Ultrasensitive Electrochemical Biomolecular Detection Using Nanostructured Microelectrodes

Abstract

Electrochemical sensors have the potential to achieve sensitive, specific, and low-cost detection of biomolecules--a capability that is ever more relevant to the diagnosis and monitored treatment of disease. The development of devices for clinical diagnostics based on electrochemical detection could provide a powerful solution for the routine use of biomarkers in patient treatment and monitoring and may overcome the many issues created by current methods, including the long sample-to-answer times, high cost, and limited prospects for lab-free use of traditional polymerase chain reaction, microarrays, and gene-sequencing technologies. In this Account, we summarize the advances in electrochemical biomolecular detection, focusing on a new and integrated platform that exploits the bottom-up fabrication of multiplexed electrochemical sensors composed of electrodeposited noble metals. We trace the evolution of these sensors from gold nanoelectrode ensembles to nanostructured microelectrodes (NMEs) and discuss the effects of surface morphology and size on assay performance. The development of a novel electrocatalytic assay based on Ru(3+) adsorption and Fe(3+) amplification at the electrode surface as a means to enable ultrasensitive analyte detection is discussed. Electrochemical measurements of changes in hybridization events at the electrode surface are performed using a simple potentiostat, which enables integration into a portable, cost-effective device. We summarize the strategies for proximal sample processing and detection in addition to those that enable high degrees of sensor multiplexing capable of measuring 100 different analytes on a single chip. By evaluating the cost and performance of various sensor substrates, we explore the development of practical lab-on-a-chip prototype devices. By functionalizing the NMEs with capture probes specific to nucleic acid, small molecule, and protein targets, we can successfully detect a wide variety of analytes at clinically relevant concentrations and speeds. Using this platform, we have achieved attomolar detection levels of nucleic acids with overall assay times as short as 2 min. We also describe the adaptation of the sensing platform to allow for the measurement of uncharged analytes--a challenge for reporter systems that rely on the charge of an analyte. Furthermore, the capabilities of this system have been applied to address the many current and important clinical challenges involving the detection of pathogenic species, including both bacterial and viral infections and cancer biomarkers. This novel electrochemical platform, which achieves large molecular-to-electrical amplification by means of its unique redox-cycling readout strategy combined with rapid and efficient analyte capture that is aided by nanostructured microelectrodes, achieves excellent specificity and sensitivity in clinical samples in which analytes are present at low concentrations in complex matrices.

Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management

“…Chip -based electrochemical sensors offer attractive solutions for clinical sample analysis, due to their high sensitivity and amenability to multiplexing (Fig. 4B) [214] [215] [195] [216] [217] [196] [218]. Electrochemical clamp assay (ECCA) can achieve detection of targets in 5 fg of isolated RNA.…”

Recent Advances on Electrochemical Biosensing Strategies toward Universal Point‐of‐Care Systems

“…As for electrochemical biosensing system, it possesses asimple and cost-effective sensing element, such as asingleuse sensor, [14] or as ensor array. [15] Thep rocessing method of bio-recognition element in an electrochemical biosensing system is simple and efficient, delivering an effective biointerface without complex operations.Furthermore,the costeffectiveness of the electric (signal) transduction system, such as linear sweep voltammetry,d ifferential pulse voltammetry,m akes the whole sensing system applicable in undeveloped areas.G enerally,t he development of electrochemical biosensing system has created ap ositive and robust impact on global health.…”

Zinc Nanoparticles-equipped Bioelectronic Nose Using a Microelectrode Array for Odorant Detection

“…16,17 But, most methods reported seemed to be complicated and expensive to mass produce, thus limiting their applications.…”