Pathogenic bacteria detection based-CBCM on MLoC and nano-amplification strategy

Human pathogenic bacteria disease is a worldwide pervasive disease. It kills more than two million people yearly, therefore, pathogenic disease is the highest disease burden as its rank is one out of four main diseases that threaten human lives. Pathogenic disease contributes to other worldwide severe diseases, such as pneumonia and causes infections such as typhoid fever, which is difficult to control at late stages. This work presents a CMOS biosensor based CBCM system that uses phage organisms to detect bacteria for different applications. The system provides a viable alternative to traditional growth-based bacterial analysis systems, which are time consuming. The system employs an interdigitated capacitor structure, charge based capacitance measurement circuitry to detect, and process capacitance changes in the presence of targeted bacteria. In this work, we concentrate on capacitive biosensor as a part of multi-labs-on-a single chip (MLoC) realized through CMOS technology.

I. Introduction

The biomedical transducers development is widespread as one of the superior industrial trends; thanks to CMOS technology that pushes forward this development and credits to MEMS technology that has also made most of the research in the domain of health detection and measurements achievable. MLoC system is one of these accomplishments credited to CMOS Technology. In this paper, CMOS-Biosensors based capacitive biosensors for biomolecular detection is proposed. The integrated biosensor is employing bacteriophage or phage organisms as recognition elements to detect deadly bacteria such as E-Coli and Salmonella at low level. The system works based on monitoring the changes in capacitance signals caused when the target bacteria are attached to the sensing interface. The system is designed using TSMC/CMOSP35 technology and it consists of interdigitated capacitor structures (MMCC) and signal detection and processing circuitry. A Charge Based Capacitance Measurement (CBCM) circuit that was originally proposed as an accurate technique for the characterization of interconnects capacitance in deep submicron CMOS ICs (Chen, McGaughy et al. 1996) does the signal detection and processing. The phage organisms are immobilized on the surface of the capacitor and together they form the sensing interface. The CMOS capacitive based sensors in implementation offer a number of advantages including small size, fast response, and low-cost mass production. Presently, much of the bacterial analysis is done in clinical laboratories, which is time consuming and requires extensive professional expertise. In addition, the majority of the available commercial devices are bulky (not suitable for field applications) and growth-based, which means that the presence of bacteria has to reach a high threshold level in order to get a reading from the apparatus. The growth-based technique is time consuming as it takes from hours to days to get the results. The proposed implementation is a real-time bacterial sensor micro-system that holds a great promise for versatile applicability in food safety, national security, and clinical diagnostics. This sensor system design falls back on the use of specific bacteriophage, which are viruses that recognize specific receptors on the bacterium surface with extreme selectivity and sensitivity. The phages bind to the surface of the bacterium and inject genetic material. Capacitive sensors offer many advantages besides their capability in straightforwardly sensing electrode motion; they can also detect conductive, or the dielectric properties of a biomaterial site onto the sensing capacitor. For that reason; the capacitance approach measurements technology is introduced as a powerful technique in biosensor applications due to its tremendous capability, stability and low-noise signal in sensing process (Baxter 2000, Serway and Jewett 2004).