ABSTRACT
More recently, instead of measuring the deflection change of a cantilever due to molecular adsorption, the label-free detection has been implemented by estimating the resonant frequency behavior of a cantilever in response to molecular adsorption onto the cantilever.11-13 The detection scheme based on the resonance of a cantilever has been receiving a significant attention due to the fact that such a detection scheme may allow the miniaturization of a cantilever. Specifically, since the resonant frequency (w) of a cantilever is inversely proportional to the square of the length of a cantilever,14 i.e., w L-2, the miniaturization of a cantilever increases its resonant frequency and, consequently, the frequency shift due to the molecular adsorption (i.e., the detection sensitivity of a cantilever). In recent years, a nanocantilever has been utilized to sense and detect the specific chemical/biological molecules even at single-molecule resolution15; this implies that the nanocantilever can be useful in detecting a single or few biological/chemical molecules, which may open a new window for the development of nanosensors whose detection limit approaches the single-molecule resolution.This chapter is aimed toward presenting the current state of the art of cantilever-based label-free detection for future applica-tions in early diagnosis of cancer, and the underlying principles for a cantilever-based detection. Section 16.2 describes physical prin-ciples, which are useful in delineating the mechanical behavior (e.g., bending and/or resonance behaviors) of a cantilever as well as understanding the underpinning mechanisms of a cantilever-based label-free detection. Section 16.3 is dedicated to recent efforts that have been made to develop the label-free biological detection based on measurement of resonance behavior of the
cantilever in response to biomolecular adsorption. Moreover, in Section 16.3, we also discuss fundamental mechanisms in cantilever-based biological detection by using physical models described in Section 16.2. Finally, in Section 16.4, we present the future per-spectives in cantilever-based biological detection for future cancer diagnosis. 16.2 Physical PrinciplesThis section reviews the fundamental principles of cantilever-based diagnosis. The early diagnosis of cancer via cantilever assay is attributed to the ability of a cantilever sensor to detect extremely minute amount of disease-specific protein molecules, DNA molecules, or RNA molecules. The detection principle of a cantilever sensor is the transduction of chemical interactions on a cantilever’s surface into the change of mechanical behavior for a cantilever. In particular, when target molecules are captured on a cantilever’s surface, where probe molecules having binding affinity with target molecules are functionalized, the molecular binding between probe molecules and target molecules lead to the change of physical properties for a cantilever, such as surface stress or the effective mass of a cantilever. The change of these physical properties can be estimated by measuring the cantilever’s bending deflection or resonant frequency. Moreover, in this section, we particularly pay attention to physical models that enable the characterization of the vibrational properties of a cantilever, since the resonating cantilever is more useful for highly sensitive detection. Here, it should be noted that the physical models described in this section are restricted to continuum mechanics model that may fail to capture the nanoscale effect, which affects the vibrational behavior of nanoscale resonator (or cantilever), since the details of molecular interactions or atomistic effects (e.g., finite size effect) are lacking in the continuum mechanics model. If the reader is more interested in multiscale models that couple atomistic model to continuum model for gaining insight into the vibrational characteristics of nanoscale resonator, they may read the review article13 that properly describes the issue of multiscale modeling as well as future perspectives in modeling that can be coupled with theory and experiments.
