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

The first ASIC prototype of a 28 nm time-space front-end electronics for real-time tracking

A front-end ASIC for 4D tracking is presented. The prototype includes the block necessary to build a pixel front-end chain for timing measurement, as independent circuits. The architecture includes a charge-sensitive amplifier, a discriminator with programmable threshold, and a time- to-digital converter. The blocks were designed with target specifications in mind including: an area occupation of 55 μm × 55 μm, a power consumption tens of micro ampere per channel and timing a resolution of at least 100 ps. The prototype has been designed and integrated in 28 nm CMOS technology. The presented design is part of the TimeSpOT project which aims to reach a high-resolution particle tracking both in space and in time, in order to provide front-end circuitry suitable for next generation colliders

A CMOS Lab-on-a-Chip for Fully Automated Telomerase Activity Detection

This paper presents a CMOS Lab-on-a-chip capable of implementing all the steps to detect the rate of activity of enzyme telomerase. 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. In order to detect the enzyme, a CMOS device integrating 1024 biosensors able to measure kinetics of DNA replication and telomerase reaction was developed. Since the activation of telomerase occurs in a very precise temperature range, the chip includes integrated temperature sensors and heaters to precisely set the working temperature. The device was designed in a standard 0.18µm CMOS process from XFAB and includes A/D conversion and a complete digital interface, all integrated within a single chip. Post-layout simulations are provided