Integrated Electronics for Molecular Biosensing

This thesis, Integrated electronics for molecular biosensing, focuses on different approaches to sense the presence and activity of a specific analyte by using integrated electronic platforms. The aim of the first platform is to detect the enzyme telomerase. Telomerase causes the elongation of telomeres, which are part of the chromosomes, and determines the lifespan of cells. Telomerase expression is a marker of malignity in tumoral cells and its evaluation can be exploited for early diagnosis of many types of cancer cells. To detect the telomerase enzyme, a CMOS (complementary metal-oxide semiconductor) biosensor based on CMFET (Charge-Modulated Field Effect Transistor) able to measure kinetics of DNA replication and telomerase reaction was developed. The sensor can be functionalized by immobilizing single strands of DNA that contain the telomeric sequence, used as probes. If telomerase is present, the probes will be elongated by the enzyme and the charge on the sensing area will change, which reflects in a variation of the output current or voltage. The chip includes three different readout schemes (voltage, current- and time-based), each of which has different measuring ranges and operating conditions. The measured data is then digitized, stored, and can be sent off-chip through SPI (Serial Peripheral Interface) protocol. A total of 1024 biosensors have been integrated in a single chip with a size of 10x10 mm2. Each sensor can be independently addressed and functionalized by an electrochemical procedure using an integrated potentiostat, thus requiring no external equipment. Although the sensors have been tailored and optimized to perform telomerase detection, the sensing areas can be functionalized to be used with different analytes. This feature turns the chip into a complete bioassay platform. The second part of this work rises from the idea that bacteria, like Escherichia coli, can detect analytes in solution even at extremely low concentrations and change their movement through a process called chemotaxis, to move towards chemical gradients in the solution. E. coli moves by rotating its flagella either clockwise (for random tumbles) or counterclockwise (for straight runs, when it senses a chemical it is attracted to). Therefore, observing bacteria flagellar rotation can give enough information on the presence of a specific analyte in the solution. To electronically detect bacteria movement, an active surface covered in electrodes has been designed. By measuring the impedance between each pair of electrodes through an integrated LIA (lock-in amplifier), it is possible to know how a single bacterium is moving. By that, the presence or absence of the analyte can be deduced, thus effectively turning bacteria into chemical sensors.