Dae Sung Yoon

Nanomechanical resonators and their applications in biological/chemical detection: Nanomechanics principles

Abstract Recent advances in nanotechnology have led to the development of nano-electro-mechanical systems (NEMS) such as nanomechanical resonators, which have recently received significant attention from the scientific community. This is not only due to their capability of label-free detection of bio/chemical molecules at single-molecule (or atomic) resolution for future applications such as the early diagnosis of diseases like cancer, but also due to their unprecedented ability to detect physical quantities such as molecular weight, elastic stiffness, surface stress, and surface elastic stiffness for adsorbed molecules on the surface. Most experimental works on resonator-based molecular detection have been based on the principle that molecular adsorption onto a resonator surface increases the effective mass, and consequently decreases the resonant frequencies of the nanomechanical resonator. However, this principle is insufficient to provide fundamental insights into resonator-based molecular detection at the nanoscale; this is due to recently proposed novel nanoscale detection principles including various effects such as surface effects, nonlinear oscillations, coupled resonance, and stiffness effects. Furthermore, these effects have only recently been incorporated into existing physical models for resonators, and therefore the universal physical principles governing nanoresonator-based detection have not been completely described. Therefore, our objective in this review is to overview the current attempts to understand the underlying mechanisms in nanoresonator-based detection using physical models coupled to computational simulations and/or experiments. Specifically, we will focus on issues of special relevance to the dynamic behavior of nanoresonators and their applications in biological/chemical detection: the resonance behavior of micro/nanoresonators; resonator-based chemical/biological detection; physical models of various nanoresonators such as nanowires, carbon nanotubes, and graphene. We pay particular attention to experimental and computational approaches that have been useful in elucidating the mechanisms underlying the dynamic behavior of resonators across multiple and disparate spatial/length scales, and the resulting insight into resonator-based detection that has been obtained. We additionally provide extensive discussion regarding potentially fruitful future research directions coupling experiments and simulations in order to develop a fundamental understanding of the basic physical principles that govern NEMS and NEMS-based sensing and detection applications.

Dominant surface stress driven by biomolecular interactions in the dynamical response of nanomechanical microcantilevers

Nanomechanical microcantilevers have played a vital role in detecting biomolecular interactions. The ability of microcantilevers to detect biomolecular interactions is ascribed to the principle that the surface stress, caused by biomolecular interactions, dominates the dynamical response of the microcantilever. Here we have experimentally studied the correlation between biomolecular interactions and the dynamical response of microcantilevers. Moreover, the authors employed a mechanical beam model to calculate the surface stress, representing the biomolecular interactions, through measuring the resonant frequency shift. The quantitative analysis of surface stress, driven by the specific protein-protein interactions, demonstrated that microcantilevers enable the quantitative study of biomolecular interactions.

AC frequency characteristics of coplanar impedance sensors as design parameters

Glass-based microchannel chips were fabricated using photolithographic technology, and Pt thin-film microelectrodes, as coplanar impedance sensors, were integrated on them. Longitudinal design parameters, such as interelectrode spacing and electrode width, of coplanar impedance sensors were changed to determine AC frequency characteristics as design parameters. Through developing total impedance equations and modeling equivalent circuits, the dominant components in each frequency region were illustrated for coplanar impedance sensors and the measured results were compared with fitted values. As the ionic concentration increased, the value of the frequency-independent region decreased and cut-off frequencies increased. As the interelectrode spacing increased, cut-off frequencies decreased and total impedance increased. However, the width of each frequency-independent region was similar. As the electrode area increased, f(low) decreased but f(high) was fixed. We think that the decrease in R(Sol) dominated over the influence of other components, which resulted in heightening f(low) and f(high). The interelectrode spacing is a more significant parameter than the electrode area in the frequency characteristics of coplanar sensors. The deviation of experimentally obtained results from theoretically predicted values may result from the fringing effect of coplanar electrode structure and parasitic capacitance due to dielectric substrates. We suggest the guidelines of dominant components for sensing as design parameters.

In situ real-time monitoring of biomolecular interactions based on resonating microcantilevers immersed in a viscous fluid

The authors report the precise (noise-free) in situ real-time monitoring of a specific protein antigen-antibody interaction by using a resonating microcantilever immersed in a viscous fluid. In this work, they utilized a resonating piezoelectric thick film microcantilever, which exhibits the high quality factor (e.g., Q=15) in a viscous liquid at a viscosity comparable to that of human blood serum. This implies a great potential of the resonating microcantilever to in situ biosensor applications. It is shown that the microcantilever enables them to monitor the C reactive protein antigen-antibody interactions in real time, providing an insight into the protein binding kinetics.

Nanobiosensors based on localized surface plasmon resonance for biomarker detection

Localized surface plasmon resonance (LSPR) is induced by incident light when it interacts with noblemetal nanoparticles that have smaller sizes than the wavelength of the incident light. Recently, LSPR-based nanobiosensors were developed as tools for highly sensitive, label-free, and flexible sensing techniques for the detection of biomolecular interactions. In this paper, we describe the basic principles of LSPR-based nanobiosensing techniques and LSPR sensor system for biomolecule sensing. We also discuss the challenges using LSPR nanobiosensors for detection of biomolecules as a biomarker.

Electrical characteristics of (100), (111), and randomly aligned lead zirconate titanate thin films

(100), (111), and randomly aligned lead zirconate titanate thin films on Pt/Ti/Corning 7059 glass substrates were prepared using a sol‐gel method. The thin films, having different alignments, were fabricated by different drying conditions for pyrolysis. The hysteresis loop and the capacitance‐voltage characteristics were investigated using a standardized ferroelectric test system. The dielectric constant and the current‐voltage characteristics of the films were investigated using an impedance analyzer and a pA meter, respectively. The microstructure was investigated using scanning electron microscopy. The (100) aligned film showed a relatively larger dielectric constant than the (111) and the randomly aligned films. The films aligned in particular directions showed higher hysteresis parameters than the randomly aligned film. The leakage current densities of the films aligned in particular directions were lower than that of the randomly aligned film.

In Situ Detection of Live Cancer Cells by Using Bioprobes Based on Au Nanoparticles

We fabricate the high-performance probes based on Au nanoparticles (AuNP) for detection of live cancer cell. AuNP were synthesized with narrow sized distribution (ca. 10 nm) by Au salt reduction method and deposited onto the aminated substrate as a cross-linker and hot spot. Herein, AuNP has enabled the easy and efficient immobilization of the antibody (Cetuximab), which can selectively interact with epidermal growth factor receptor (EGFR) on the surface of epidermal cancer, as detecting moiety onto the AuNP-deposited substrate without nanolithography process. After conjugation of Cetuximab with AuNP-deposited substrate, Cetuximab-conjugated probe as a live cancer cell detector (LCCD) could detect EGFR-highexpressed A431 cells related to epithelial cancer with 54-times larger specificity and sensitivity in comparison with EGFR-deficient MCF7 cells. This implies that AuNP-based probes demonstrate abundant potentials for detection and separation of small biomolecules, cells and other chemicals.

Epitaxial growth of sol-gel PLZT thin films

Epitaxial lead lanthanum zirconate titanate [PLZT(9/50/50)] thin films were fabricated on various single crystal substrates using the spin coating of metallo-organic solutions. The films were heat-treated at 700 °C for 1 h using the direct insertion method. The films were epitaxially grown with (100), (100), and (110) being parallel to the SrTiO 3 (100), the MgO(100), and the sapphire (01 1 2) substrates, respectively. The epitaxy of the films was investigated using x-ray diffraction, pole figures, rocking curves, and scanning electron microscopy.

Investigation of the drying temperature dependence of the orientation in sol–gel processed PZT thin films

The crystal orientations of lead zirconate titanate (PZT) thin films have been investigated by using various drying temperatures in the sol–gel process. The films were dried at different temperatures between 310 and 350°C for pyrolysis and then were heat treated at 650°C using rapid thermal annealing (RTA). TG/DTA and FTIR spectroscopy were used to detect the remnants of organic materials in the thin films prior to the final heat treatment. In order to examine the relationship between the film orientation and the remaining organic materials for the prior and final heat treatment, the films were fabricated with different coating cycles and dried for different holding times and then annealed at 650°C. The preferred orientations were investigated using X-ray diffraction.

Micromechanical observation of the kinetics of biomolecular interactions

Resonant microcantilevers have recently enabled the label-free detection of biomolecules. Here, we observed the kinetics of biomolecular interactions such as antigen-antibody interactions and/or DNA hybridization based on a resonant frequency shift, obeying Langmuir kinetics, measured in a buffer solution. It is shown that the kinetics of DNA adsorptions on the surface is governed by intermolecular interactions between adsorbed DNA molecules. It is also shown that the kinetics of DNA hybridization is determined by the intermolecular interaction. It is implied that resonant microcantilever in buffer solution may allow for gaining insights into the kinetics of various molecular interactions.