ABSTRACT:The detection of mismatched base pairs in DNA plays a crucial role in the diagnosis of genetic-related diseases and conditions, especially for early stage treatment. Among the various biosensors that have been used for DNA detection, EC sensors show great promise because they are capable of precise DNA recognition and efficient signal transduction. Advancements in micro-and nanotechnologies, specifically fabrication techniques and new nanomaterials, have enabled for the development of highly sensitive, highly specific sensors making them attractive for the detection of small sequence variations. Furthermore, the integration of sensors with sample preparation and fluidic processes enables for rapid, multiplexed DNA detection essential for POC clinical diagnostics. T he recent discovery and sequencing of the human genome has provided valuable insight into understanding how genetic factors contribute to the development of disease. Specifically, the detection of DNA sequence variations plays an important role in the diagnosis of genetic-related diseases and conditions, especially for early stage treatment and monitoring. Among the different types of diseases caused by DNA alterations, sequence-specific mismatch has the most importance, yet is extremely difficult to detect (1), especially for single-nucleotide polymorphism (SNP). Furthermore, sequence-specific detection has great importance in various medical and scientific applications such as the diagnosis of inherited diseases and the study of pathogen response and bacterial/viral detection.Because of the complex nature of DNA, the detection of single or small numbers of base mismatches requires high sensitivity and specificity (2-4). Current detection methods rely on sample amplification combined with meticulous experimental stringency control (5). For example, polymerase chain reaction (PCR) requires careful primer design and accurate temperature control to obtain sensitivities in the fM range with single-base mismatch specificity (1,3,4). Although these conventional technologies provide the golden standard for laboratory-based DNA diagnostics, they cannot meet the requirements of POC clinical diagnostics (4).EC sensors, initially developed to detect biomolecules in a laboratory setting, have recently found extensive applications for on-site biosensing and detection (6,7), especially for medical and clinical diagnostics (8 -12). While offering simplicity in operation and sample manipulation, the contemporary EC biosensor also provides highly sensitive and specific measurements for a broad spectrum of biomolecules (13-17). The sample size required for current EC sensors is small, ranging from several microliters to hundreds of nanoliters, which includes the sample pretreatment reagents. Additionally, the detection time is relatively fast, varying from a few minutes to tens of seconds. However, the most important feature of EC sensors is their potential to be easily transformed from a laboratory-based instrument to a commercializable POC device. Because o...