## 1 Introduction  
The conventional sensing methods in medicine and life sciences require expensive reagents, high-precision instruments, and quantitative methods to achieve highly sensitive detection. Thus, many novel nano-biosensors have been developed due to the need for early detection and diagnosis of the disease, as well as minimally invasive detection approaches [1; 2; 3; 4; 5]. The integration of biosensors with nanotechnology has facilitated the considerable progress of biosensor development. The nano-sized nature of nanomaterials and their unique chemical and electrical properties have promoted the enhancement of both selectivity and sensitivity at a very low concentration on the biosensors [1; 2; 3; 6]. Generally, biosensors consist of three basic elements: bioreactor, transducer, and detector. A bioreactor is an element that reacts with the analyte (bacteria, complementary DNA, antigen, etc.) in the form of (enzyme, DNA probe, antibacterial, etc.). The employment of enzymes is widely used in biosensors. It is also responsible for binding the dedicated form to the object (sample). With respect to the bioreactor elements and their interaction types, there are two types of sensors. Catalytic sensor--a signal that converts the substrate to a product after binding the analyte with biological elements without any chemical change A\(\leftrightarrow\)B where the transducer receives A or B input. Affinity sensor-biological elements and the analyte interact with each other and their output is the detected complex event A*B\(\rightarrow\)AB where the transducer reveals the complex interaction [7; 8; 9]. The transducer is an element which converts the (bio) chemical signal to an electrical signal to be measured. The principle of detection depends on the type of used transducer signal and biorecognition elements which lead directly to correlate with the analyte concentration inversely or proportionally [10]. The electronic system (detector) is responsible for receiving the transducer signal and amplifying it using a signal amplifier, and then sending it to be processed by the computer. The computer could read the amplified signal and convert it to readable data that have magnificent physical investigated parameters [7], as presented in Figure 1.  
Nano-biosensors can be categorized according to the basic detection principles of signal transduction and biorecognition elements into three main types: (1) Electrochemical detection principles, (2) optical detection principles, and (3) mass detection principles [6]. In comparison with other detection approaches, electrochemical sensors for multiple analytes were the first scientifically proposed as well as successfully commercialized biosensors. This stems from several remarkable electrochemical abilities including the high sensitivity of electrochemical transducers (such as the cyclic voltammeter transducer), their compatibility with modern technologies, simplicity, and low detection limit [6; 11]. The fundamental principle of electrochemical biosensors is that the chemical reaction between the immobilized biomolecule and target analyte produces or consume ions or electrons, which affects readable electrical properties of the solution such as electric current, voltage, and resistance. Each reaction can be represented by a simple electric circuit model and the electrochemical signal produced is then used to relate quantitatively to the amount of analyte [11; 12]. The biosensors benchmarks depend on its linearity (maximum linear value of the sensor calibration curve responding to the glucose. Good linear sensors would detect high substrate concentrations), sensitivity (the value of the electrode response per substrate concentration. Highly sensitive sensors could be detected at low concentrations), selectivity (interference of chemicals must be minimized for obtaining the correct result), and response time (the necessary time for having 95% of the response).