Sheng D. Chao

Simulation on binding efficiency of immunoassay for a biosensor with applying electrothermal effect

The working principle of immunoassays is based on the specific binding reaction of an analyte-ligand protein pair in physiological environments. However, for a diffusion-limited protein, the diffusion boundary layer of the analyte on the reaction surface of a biosensor would hinder the binding reaction from association and dissociation. The formation of such association and dissociation layers thus limits the response time and the overall performance of a biosensor. In this work we have performed a two-dimensional full time scale finite element simulation on the binding reaction kinetics of two commonly used proteins, C-reactive protein (CRP) and immunoglobulin G (IgG). By applying a nonuniform ac electric field to the flow microchannel of the biosensor, the electrothermal force can be generated to induce a pair of vortices to stir the flow field. With the aid of the vortices and a suitable choice of the location of the biosensor, the fluids flowing over the reacting surface can be accelerated fast enough...

Two dimensional simulation on immunoassay for a biosensor with applying electrothermal effect

For diffusion-limited proteins, the diffusion boundary layer on the reacting surface hinders the binding reaction. The authors performed finite-element simulations of the electrothermal effect on the reaction kinetics of C-reactive protein (CRP)–anti-CRP. The induced vortices stir the flow and enhance the transport rate of analytes. They attribute the enhancement to the reduction of the thickness of diffusion boundary layer. Significant interference patterns of the votices are observed by varying the position of the reacting surface. These patterns are utilized to optimize the enhancement factor, yielding 5.166 and 3.744 times for association and dissociation, respectively, under voltage (15Vrms) and frequency (100kHz).

Effects of diffusion boundary layer on reaction kinetics of immunoassay in a biosensor

Specific binding reaction is a natural characteristic that is applied to design biosensors. This work simulates the binding reaction kinetics of two commonly used proteins, C-reactive protein and immunoglobulin G, in a reaction chamber (microchannel) of a biosensor. For a diffusion-limited protein, the diffusion boundary layer on the reaction surface of the biosensor would hinder the binding reaction from association and dissociation. Several crucial factors, which influence the binding reaction curves in the simulation, are discussed, including the concentration of analyte, the inlet flow velocity, the channel height, and the length of the reaction surface. A higher channel causes the diffusive transport of the analyte to take longer time to reach the reaction surface, which in turn decreases the reaction rate of the protein pairs. The length of the reaction surface plays an important role in the formation of the boundary layer. For longer reaction surface, it takes more time to allow diffusion to overco...

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.

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.

Study of Active Micromixer Driven by Electrothermal Force

Biochemical applications of microchips often require a rapid mixing of different fluid samples. At the microscale level, fluid flow is usually a highly ordered laminar flow and diffusion is the primary mechanism for mixing owing to the lack of disturbances, yielding inefficiency for practical biochemical analysis. In this work, we design a prototype active micromixer by employing the electrothermal effect. We apply to the flow microchannel a non-uniform AC electric field, which can generate an electrothermal force on the fluid flow and induce vortex pairs for enhancing mixing efficiency. The performance of this active micromixer is studied and compared, under the same mixing quality, with that of a conventional passive micromixer of the same size with obstacles in the flow channel by three-dimensional finite element simulations. The numerical results show that the pressure drop between the inlet and the outlet for the active micromixer is much less than (only 3000th) that for the passive micro-mixer with the same mixing quality. To obtain an optimal mixing quality, we have systematically studied the mixing quality by varying the geometrical arrangements of the electrodes. An almost complete mixing can be obtained using a specific design. Moreover, the temperature increases around the electrodes are lower than 3 K, which does not adversely affect the biochemical analysis. It is suggested that the prototype active micromixer designed is promising and effective and useful for biochemical analysis.

Beam model and three dimensional numerical simulations on suspended microchannel resonators

At the microscale level, the vibrational characteristics of microstructures have been widely applied on biochemical microchips, especially for bio-molecules detection. The vibrational mechanics and mechanism of microcantilever beams immersed in the fluids for detecting target bio-molecules carried in the fluids have been widely studied and realized in recent years. However, it is not the case for microcantilever beams containing fluids inside (called suspended microchannel resonators, SMR). In this paper, an 1-D beam model for SMR is proposed and the formula for prediction of resonant frequency and resonant frequency shift are derived. For verification of validity of the 1-D beam model, three dimensional finite element simulations using ANSYS are performed. The effects of relevant parameters, such as density and viscosity of the fluids, on the frequency response are investigated. A link between numerical simulations and mathematical modeling is established through an equivalence relation. Subsequently, a ...

Reduced dimensional analysis on dynamic characteristics of microcantilever beams in the fluid environment and application to atomic force microscopy

This paper is mainly aimed to investigate the dynamic characteristics of a microbeam structure located at the neighborhood of a wall inside the chamber filled with different fluids. Firstly, by solving the Reynolds equation and the Euler beam equation, specific dynamic characteristics of the entire system such as the resonant frequency, the frequency shift, and the damping ratio can be obtained. Secondly, by relating the calculated dynamic characteristics to the frequency response of a reduced dimensional system, the effective mass, damping and stiffness can be evaluated for the beam structure in the fluid near the chamber wall. The coupling dynamic behavior can be understood by analyzing these extended physical parameters, namely, the effective mass, damping and stiffness. Finally, the preceding analytic procedure is used to demonstrate the limitation on the tip size of the probe of an atomic force microscope operated in non-contact mode within fluid environment.

Surface dipole induced by alkanethiolate adsorbated on Au(111)

The surface dipoles induced by alkanethiolates adsorbated on Au(lll) surface are studied by means of the state-of-the-art first-principles calculations. Two models of Alkanethiolate and Au adatom-alkanethiolate moieties on Au(lll) surface are adapted in this work. Charge transfer from gold surface to alkanethiolate cause electrostatic dipoles on the gold surface. It was found that a net charge transfer of 0.09e ~0.15e from gold surface to alkanethiolate molecules. Most of the transferred charge is accumulated in the carbon atom which is nearest to the sulfur atom.

Finite-Element Simulation on Electrothermal Effects for Immuno-Biosensors

For a diffusion-limited protein, the diffusion boundary layer of the analyte formed on the reaction surface hinders the binding reaction from association and dissociation. With a non-uniform AC electric field, the electrothermal force generates a pair of stirring vortices to increase the transport of the analytes to the reaction surface and thus to enhance the association or dissociation of analyte-ligand complex. This work simulates a 2-dimensional full scale finite element analysis of the binding reaction kinetics of two commonly used proteins, CRP and IgG, by applying a non-uniform AC electric field. In addition to the electrothermal stirring effect, the blocking effect of the flow field due to the existence of the reaction surface at different positions of the micro-channel could cause different degrees of enhancement to the association and the dissociation. The largest enhancement is found at the position near the negative electrode. The initial slope of the curve of the analyte-ligand complex versus time can be raised up to 5.166 times for CRP and 1.934 times for IgG in association; and 3.744 times for CRP and 1.277 times for IgG in dissociation, respectively, with a field 15 Vrms peak-to-peak and operating frequency 100 kHz.Copyright