ABSTRACT

Tacitly, the traditional trend in health care, concentrating on the treatment of diseases, has been slowly replaced by early diagnosis to prevent disease. In order to keep step with the trend, the need for high-performance biosensors has attracted attention as a viable tool in healthcare systems. One of the most essential features for a high-performance biosensor is high sensitivity. Nanotechnology, which has advanced rapidly, can be a powerful tool for improving the sensitivity of biosensors through maximization of the surfaceto-volume ratio (SVR), allowing a small amount of change by biomolecules placed onto their surfaces to be monitored. In general, the limit of detection (LOD) of a biosensor is mainly limited by the dissociation constant (Kd), which is related to the thermodynamics of the affi nity reaction. In the case of an antibody-antigen reaction for protein detection, the Kd value is 10

–8~10-12 M; it is 10-15 M for the streptavidin-biotin reaction, which is known as the strongest binding affi nity in nature (Bayer and Wilchek 1990). As a result, 10-9~10-14 M represents the lowest LOD range that can be acquired from a conventional biosensor. Therefore, in order to attain improved sensitivity, amplifi cation methods such as the polymerase chain reaction (PCR) method are necessary. However, such an amplifi cation method requires a labeling process, which inevitably involves time-consuming labor and pretreatment steps, which in turn demand skilled operators and specialized expensive equipment. In addition, these methods are associated with constraints in terms of real-time detection and result in unreliable data owing to the loss of samples during the manipulation steps. Recently, biosensor building blocks with a range of 1 to 100 nm in size were developed with the aid of nanotechnology. The nanoscale building blocks provide a size-matched interface between biomolecules and the biosensor system because the size of the building block is comparable to the size of the biomolecule, such as DNA, protein, and virus, which can cause disease (Fig. 9.1). Moreover, these building blocks show high sensitivity without extra amplifi cation

steps due to the high SVR, which is an inherent property of the nanoscale structure. Cantilever, quantum dot or nanoparticle (0-dimension), nanobelts (2-dimension), nanogaps (>2-dimension), nanotube (1-dimension), and nanowire (1-dimension)-based biosensors are typical biosensors that utilize such nanostructures. Among them, cantilever and quantum dot biosensors or those based on nanoparticle show extremely high sensitivity, selectivity, and a short response time. However, the requirement of massive and expensive equipment for their proper operation hinders these biosensors from being applied to chip-based biosensors. On the other hand, fi eld effect transistor (FET)-based biosensors, such as nanotubes, nanobelts, nanogaps, and nanowires, do not require this type of equipment. Hence, they are proper candidates for application to chip-based biosensors (Patolsky et al. 2006a; Curreli et al. 2008). FET-based biosensors respond to the charges arising from target molecules and therefore allow label-free detection without pre-or post-treatments which are a risk sacrifi cing time, cost, and sample loss. They exhibit suffi ciently high sensitivity (~ fM) to detect disease markers despite the fact that their sensitivities are lower than the sensitivity levels of the cantilever and quantum dot-based biosensors. One of the advantages of electrical biosensors is free of a transducer, which converts one signal to another type of signal because both the input and output signals are composed of electrical signals. For example, optical, chemical, mechanical, or biological signals have to be transformed to electrical signals, which can be directly displayed in an electronic terminal device for non-electrical biosensors. This advantage of the FET-based biosensors makes them promising candidates for chip-based point-of-care testing (POCT) systems. Among the FET-based biosensors, silicon nanowire (SiNW) has attracted a considerable amount of attention due to its simple fabrication, integration, and well-understood underlying physics by virtue

of the matured silicon technology. Thus, in this chapter, SiNW biosensors are primarily discussed in depth.