Nanomechanical cantilever devices for biological sensors

In the last 20 years, technology has been divided into many subtechnologies. For example, mechatronics has been divided into microelectromechanical systems (MEMS) or nanoelectromechanical systems (NEMS). Furthermore, various subtechnologies such as MEMS, NEMS and biotechnology have been combined to form new fields such as nanobiotechnology. These dramatic technological changes are due to the efforts of researchers to overcome the technological hurdles faced by conventional technology. With respect to nanobiotechnology, there is great interest in micromechanical biosensors and nanomechanical biosensors that use the nanomechanical technology of MEMS and NEMS. Micromechanical and nanomechanical biosensors are devices that measure physical quantities by utilizing variations in the physical properties of specifically fabricated microstructures that originate from biological interactions. In microcantilever biosensors, the cantilever transduces the recognition event from its receptor immobilised surface (for example, a DNA probe and an antigen or antibody) into a mechanical response (for example, static displacement and resonance frequency). The mechanical response can then be detected with different methods. Advances in MEMS and NEMS technology have facilitated the development of microcantilever biosensors and they have given the biosensors many advantages. For example, a greatly reduced size, high sensitivity, increased minimum detectable sensitivity, and greater reliability. Furthermore, these advances have enabled existing devices to be scaled down to a micrometer regime or even a nanometer regime. As a result, these devices have better sensitivity. As devices are fabricated on a microscale or even a nanoscale, they offer us an opportunity to explore new basic scientific phenomena that occur only when the dimensions are small (for example, the binding force measurements of protein folding and DNA hydrogen bonding). Although biosensing tools are currently undergoing a further stage of development, a remarkable breakthrough is needed to obtain a biosensor system that is practical and portable. Arntz et al. suggested the following primary requirements for a future generation of biosensors (Arntz et al. 2003): • The combination of a biologically sensitive part with a physical transducer for specific and quantitative detection of analytes • The ability of label-free detection of the biological interaction • The scalability of the sensors to allow massive parallelisation • Sensitivity of the detection range applicable for in vivo problems A microcantilever biosensor is compatible with these requirements. Compared with other mechanical biosensors based on quartz crystal microbalance and surface acoustic waves, the microcantilever biosensor has strong potential for parallelisation and scalability. Another advantage of the microcantilever biosensor is that it is basically a label-free and highly sensitive device. Further, they have peculiar properties of inducing static deformation or resonance frequency shifts that are related to biological interactions such as antigen-antibody binding and DNA hybridisation. The biological application of cantilevers is a promising field in academic and industrial research because of their usefulness in various biological tests such as bioassays and the binding force measurement of biomolecule-biomolecule interactions. Another trend in microcantilevers is that the dimensions of a mechanical cantilever are still being reduced, and this trend indicates the advent of a new generation of NEMS. Scaling down the dimensions of microcantilevers improves sensitivity, spatial resolution, energy efficiency and the speed of response. Furthermore, the scale-down is expected to achieve a mass sensitivity of around 10^-19 g (Davis et al. 2000). As a result, nanomechanical cantilevers will be able to detect specific molecular interactions, cell adhesion and chemical gases with miniscule quantities. The combination of a scaled-down cantilever and the nanoscale phenomena that occur on the surface of the cantilever give the sensor an ability that is up to or beyond the femto and atto regime. In this chapter, we introduce two types of micromechanical biosensors: a microcantilever and a nanocantilever. The schematics to explain the basic principles of a cantilever's mechanics and detection scheme are presented. The summary of various methods of microcantilever fabrication is given. The discussion on measurement and readout techniques is included. Many bioassay examples with reference to categories such as DNA, protein, and cell detection are also given. Finally, we analyse the current status of microcantilever biosensors and discuss various breakthroughs that are needed for the popularisation and commercialisation of microcantilevers.