Enabling technologies for CMOS-compatible MEMS biosensors

The goal of the research presented in this doctoral thesis is to achieve important insights towards the realization of highly sensitive and compact devices for biological sensing. Current research activities on biosensors have a common denominator, i.e. they aim at obtaining miniaturization and portability. Micro and Nano Electro-Mechanical Systems (MEMS and NEMS, respectively), when integrated with Complementary Metal-Oxide-Semiconductor (CMOS) substrates, offer excellent opportunities for the achievement of highly-sensitive and miniaturized sensors for biomedical applications. Micro-mechanical mass sensors are microfabricated resonant transducers whose mass changes upon surface grafting of the chemical or biological entities of interest. The shift in mass causes a resonance frequency variation, allowing the recognition of the desired analyte. Among the most widely utilized techniques for actuation and sensing are optical and piezoelectric ones. Electrostatic actuation allows higher compactness, but requires electrodes that are very closely spaced. This easily causes stiction, especially in humid biological environments. We propose the investigation of micro-mechanical resonators with electrostatic actuation and readout, whose design has been optimized to avoid stiction. To increase their sensitivity, the surface to volume ratio has been increased by using a special resonator design. We use polycrystalline silicon-germanium (poly-SiGe), which is known to be an excellent material for MEMS monolithic integration with the CMOS electronic circuitry and which is new to biomedical applications. The poly-SiGe technology has been developed at IMEC (Belgium). In parallel, the in vitro biocompatibility of poly-SiGe was explored and a protocol for selective and covalent binding of proteins developed (collaboration between the University of Pisa and the CNR of Pisa). 3-aminopropyl-triethoxysilane (APTES) active areas were defined on top of poly-SiGe surfaces by silane deposition onto photoresist patterns and lifted off in organic solvents, and proteins (albumin or antigen-antibody pairs) were covalently bound on the created APTES patterns. Protein binding inside the desired bioactive areas and low non-specific adsorption outside the APTES pattern was shown. Furthermore, the quality of the silane patches was investigated by treatment with 30 nm-diameter gold nanoparticles (Au NPs) and scanning electron microscope (SEM) observation. Piezoresistive poly-SiGe sensors are studied as well. Piezoresistivity is widely employed as a readout method in MEMS and BioMEMS (biomedical MEMS) applications and allows CMOS integration. The piezoresistive properties of polycrystalline and microcrystalline SiGe were experimentally evaluated and a poly-SiGe piezoresistive torsional displacement sensor is presented.