A Co-Printed Nanoslit Surface Plasmon Resonance Structure in Microfluidic Device for LMP-1 Detection.

This paper reports a novel micro/nanostructure co-hot embossing technique. Gold-capped nanostructures were used as localized surface plasmon resonance (SPR) sensors and were integrated into a microfluidic channel. The advantage of the co-hot embossing technique is that the SPR sensors do not need to be aligned with the microfluidic channel while bonding to it. The integrated SPR sensor and microfluidic channel were first characterized, and the sensitivity of the SPR sensor to the refractive index was found using different concentrations of glycerol solutions. The SPR sensor was also used to quantify latent membrane protein (LMP-1) when modifying anti-LMP-1 at the surface of the SPR sensor. Different concentrations of LMP-1 samples were used to build a calibration curve.

Improving the binding efficiency of quartz crystal microbalance biosensors by applying the electrothermal effect.

A quartz crystal microbalance (QCM) serving as a biosensor to detect the target biomolecules (analytes) often suffers from the time consuming process, especially in the case of diffusion-limited reaction. In this experimental work, we modify the reaction chamber of a conventional QCM by integrating into the multi-microelectrodes to produce electrothermal vortex flow which can efficiently drive the analytes moving toward the sensor surface, where the analytes were captured by the immobilized ligands. The microelectrodes are placed on the top surface of the chamber opposite to the sensor, which is located on the bottom of the chamber. Besides, the height of reaction chamber is reduced to assure that the suspended analytes in the fluid can be effectively drived to the sensor surface by induced electrothermal vortex flow, and also the sample costs are saved. A series of frequency shift measurements associated with the adding mass due to the specific binding of the analytes in the fluid flow and the immobilized ligands on the QCM sensor surface are performed with or without applying electrothermal effect (ETE). The experimental results show that electrothermal vortex flow does effectively accelerate the specific binding and make the frequency shift measurement more sensible. In addition, the images of the binding surfaces of the sensors with or without applying electrothermal effect are taken through the scanning electron microscopy. By comparing the images, it also clearly indicates that ETE does raise the specific binding of the analytes and ligands and efficiently improves the performance of the QCM sensor.

First-principles surface stress calculations and multiscale deformation analysis of a self-assembled monolayer adsorbed on a micro-cantilever.

Micro-cantilever sensors are widely used to detect biomolecules, chemical gases, and ionic species. However, the theoretical descriptions and predictive modeling of these devices are not well developed, and lag behind advances in fabrication and applications. In this paper, we present a novel multiscale simulation framework for nanomechanical sensors. This framework, combining density functional theory (DFT) calculations and finite element method (FEM) analysis, is capable of analyzing molecular adsorption-induced deformation and stress fields in the sensors from the molecular scale to the device scale. Adsorption of alkanethiolate self-assembled monolayer (SAM) on the Au(111) surface of the micro-cantilever sensor is studied in detail to demonstrate the applicability of this framework. DFT calculations are employed to investigate the molecular adsorption-induced surface stress upon the gold surface. The 3D shell elements with initial stresses obtained from the DFT calculations serve as SAM domains in the adsorption layer, while FEM is employed to analyze the deformation and stress of the sensor devices. We find that the micro-cantilever tip deflection has a linear relationship with the coverage of the SAM domains. With full coverage, the tip deflection decreases as the molecular chain length increases. The multiscale simulation framework provides a quantitative analysis of the displacement and stress fields, and can be used to predict the response of nanomechanical sensors subjected to complex molecular adsorption.

Integrating fault tolerance algorithm and circularly polarized ellipsometer for point-of-care applications.

A circularly polarized ellipsometer was developed to enable real-time measurements of the optical properties of materials. Using a four photo-detector quadrature configuration, a phase modulated ellipsometer was substantially miniaturized which has the ability to achieve a high precision detection limit. With a proven angular resolution of 0.0001 deg achieved by controlling the relative positions of a triangular prism, a paraboloidal and a spherical mirror pair, this new ellipsometer possesses a higher resolution than traditional complex mechanically controlled configurations. Moreover, the addition of an algorithm, FTA (fault tolerance algorithm) was adopted to compensate for the imperfections of the opto-mechanical system which can decrease system measurement reliability. This newly developed system requires only one millisecond or less to complete the measurement task without having to adopt any other modulation approach. The resolution achieved can be as high as 4x10(-7) RIU (refractive index unit) which is highly competitive when compared with other commercially available instruments. Our experimental results agreed well with the simulation data which confirms that our quadrature-based circularly polarized ellipsometer with FTA is an effective tool for precise detection of the optical properties of thin films. It also has the potential to be used to monitor the refractive index change of molecules in liquids.

Detection of C-reactive protein in evanescent wave field using microparticle-tracking velocimetry.

A new technique is developed to measure the nanoparticles' brownian motions by employing microparticle-tracking velocimetry (micro-PTV) in evanescent wave field, which can provide high signal-to-noise ratio images for analyzing nanoparticles' movements. This method enables real-time detection of C-reactive proteins (CRPs) during the rapid interaction between CRPs and anti-CRP-coated nanobeads as CRP concentrations are related to the nanobeads' brownian velocity in the equilibrium state. The smallest observable nanobeads with 185 nm were utilized in this experiment to detect CRP concentrations as low as 0.1 microg/mL even in a high-viscosity solution. Further, the dissociation constant, K(D), can be evaluated based on the experimental results.

A combined experimental and theoretical study on the immunoassay of human immunoglobulin using a quartz crystal microbalance.

We investigate a immunoassay biosensor that employs a Quartz Crystal Microbalance (QCM) to detect the specific binding reaction of the (Human IgG1)-(Anti-Human IgG1) protein pair under physiological conditions. In addition to experiments, a three dimensional time domain finite element method (FEM) was used to perform simulations for the biomolecular binding reaction in microfluidic channels. In particular, we discuss the unsteady convective diffusion in the transportation tube, which conveys the buffer solution containing the analyte molecules into the micro-channel where the QCM sensor lies. It is found that the distribution of the analyte concentration in the tube is strongly affected by the flow field, yielding large discrepancies between the simulations and experimental results. Our analysis shows that the conventional assumption of the analyte concentration in the inlet of the micro-channel being uniform and constant in time is inadequate. In addition, we also show that the commonly used procedure in kinetic analysis for estimating binding rate constants from the experimental data would underestimate these rate constants due to neglected diffusion processes from the inlet to the reaction surface. A calibration procedure is proposed to supplement the basic kinetic analysis, thus yielding better consistency with experiments.

A quantitative immunosensing technique based on the measurement of nanobeads' Brownian motion.

A novel bio-sensing technique based on the measurement of nanobeads' Brownian motion using a micro-particle tracking velocimetry (micro-PTV) has been successfully developed to detect antigen-antibody interactions. The rapid interaction between antigens (C-reactive proteins, CRPs) and nanobeads with conjugated antibodies (anti-CRPs) has enabled real-time detection of CRPs to be easily carried out. During the binding process of CRPs to nanobeads, the mean value of the beads' diameters increases so that the Brownian velocity decreases with the increase of time. Moreover, higher CRP concentration leads to a lower Brownian velocity of the nanobeads in the equilibrium state. From the results, the limit of detection 0.1microg/ml was observed and could be further improved by using smaller nanobeads. Moreover, based on kinetic analysis, the average dissociation constant K(D)=(6.48+/-1.43)x10(-7) found by this technique for anti-CRP was shown to be in close agreement with the literature values obtained by dual-polarization interferometry (DPI) and indirect competition enzyme-linked immunosorbent assay (ELISA). This simple sensing method can further be used to detect other bio-molecules and viruses.

Continuous numerical aperture properties of a cylindrically polarized light illuminated sub-wavelength annular aperture.

We investigated the process of focusing a radially polarized (RP) light beam through a sub-wavelength annular aperture (SAA). We found that the result was a non-diffraction doughnut-shaped light beam which propagates in free space. After analyzing the electric field component of the focus generated by the SAA structure, we identified the relationship between the focal field generated by the SAA. We then compared it to a case with a traditional objective lens. From our findings, we propose that a SAA structure can be viewed as a continuous numerical aperture optical element.

Photorefractive crystal-based holographic interferometry system for full-field wave propagation metrology.

Although, photorefractive materials have been discovered for many years, research using pulsed laser as the light source and photorefractive material as the recording media to record a pulsed laser hologram have been scarce despite its vast application potential. A newly proposed optical configuration which adopts a Nd:YAG pulsed laser of 532nm wavelength as the light source and uses an iron-doped lithium niobate crystal as the recording media for holographic recording of an un-deformed specimen is presented. Real-time holographic interferometry was achieved by inducing repetitive impacts on the specimen through a precise piezoelectric impact hammer. With timing control better than microseconds, several interferograms created at each instance were obtained with each corresponding 9ns laser pulse. A five-step phase-shifting technology, median filter algorithm, and weighted iterative DFT phase unwrap algorithm were integrated to reconstruct the deformation information at each instance. Using a series of measured deformation data, surface wave propagation phenomenon on the specimen could be observed. Some of the potential applications for this newly developed pulsed laser holographic interferometry system are detailed.

Enhancement and tunability of active plasmonic by multilayer grating coupled emission.

The effect of coupled mode surface plasmon polaritons (SPPs) on the active emission of a nanostructure grating with organic semiconductor material, Alq(3), on the surface was investigated in this study. We report surface plasmon grating coupled emission (SPGCE) from excited organic layer on metal grating in both organic/metal (2-Layer) and organic/metal/organic/metal (4-Layer) structures. The dispersion relation was obtained from angle-resolved photoluminescence measurement. The resultant emission intensity can have up to 6 times enhancement on the 4- Layer device and the Full-Width Half-Maximum (FWHM) is less than 50 nm. The combination of SPPs on organic/metal interface allows specific directional emission and color appearance of Alq(3) fluorophores. Potential applications of such an active plasmonics with enhanced resonant energy emission due to interactions on the organic/metal nano-grating as biosensor were presented and discussed.

A new 1-D integral representation for dynamic response of anisotropic elastic solids due to a point force.

A new 1-D integral is presented for calculating the transient response due to a suddenly applied point force in a general anisotropic solid. The integral is based on a 2-D solution for a line force. It is shown that the integral reduces to a simple expression for the static Green's function immediately after the passage of the last bulk wave. The computational efficiency and accuracy of the proposed formulation are demonstrated by numerical examples for zinc and copper.

Phase-shifting algorithms for electronic speckle pattern interferometry.

A set of innovative phase-shifting algorithms developed to facilitate metrology based on electronic speckle pattern interferometry (ESPI) are presented. The theory of a phase-shifting algorithm, called a (5,1) algorithm, that takes five phase-shifted intensity maps before a specimen is deformed and one intensity map after a specimen is deformed is presented first. Because a high-speed camera can be used to record the dynamic image of the specimen, this newly developed algorithm has the potential to retain the phase-shifting capability for ESPI in dynamic measurements. Also shown is an algorithm called a (1,5) algorithm that takes five phase-shifted intensity maps after the specimen is deformed. In addition, a direct-correlation algorithm was integrated with these newly developed (5,1) or (1,5) algorithms to form DC-(5,1) and DC-(1,5) algorithms, which are shown to improve significantly the quality of the phase maps. The theoretical and experimental aspects of these two newly developed techniques, which can extend ESPI to areas such as high-speed dynamic measurements, are examined in detail.