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

Abstract

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 ͑CRP͒ and immunoglobulin G ͑IgG͒. 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 to depress efficiently the growth of the diffusion boundary layer on the reaction surface, and enhance the association or dissociation of analyte-ligand complex. The interference patterns of the flow field due to the existence of the sensor at different locations of the microchannel could cause different degrees of enhancement to the association and the dissociation. By changing the location of the sensor the largest enhancement is found at the position near the negative electrode. For the configuration of the microchannel we studied, the initial slope of the curve of the analyte-ligand complex versus time can be raised up to 5.17 for CRP and 1.93 for IgG in association, and 3.74 for CRP and 1.28 for IgG in dissociation, respectively, under the applied ac field 15 V rms peak-to-peak and operating frequency 100 kHz. At this optimal sensor location, we also studied the effect of various settings of temperature boundary conditions on the top and bottom walls, including the two limiting cases, namely, constant temperature and thermal insulation on both walls. We show that varying the temperature boundary conditions can cause an essential effect on the enhancement of the binding reaction and can be employed to find an optimal binding enhancement. Utilizing these simulation results, an improved design incorporating a pair of electrodes and a neck region near the reaction surface is demonstrated. The sensor is fixed to locate at the middle of the bottom side. With the existence of the stirring flow field, the association rate of the 30 m neck is 2.73 times faster than that of the original channel with no neck.

Study of the effect of electric field and electroneutrality on transport of biomolecules in microreactors

“…The field strengths used in this study is in the order of 10-100 V/cm which is far below the critical value (2500 V/cm) introduced in the study of Ermakov et al (1998). The reader is referred to a series of articles by Das et al (2006), Sigurdson et al (2005), Feldman et al (2007), Yang et al (2007), and Huang et al (2008) for more details on the effect of electrothermal phenomena when they are not negligible.…”

“…The counterions gathered around the biomolecule are responsible for this charge reduction. In all previous studies (Kassegne et al 2003;Chatterjee 2003;Sigurdson et al 2005;Das et al 2006;Das and Chakraborty 2007;Feldman et al 2007;Yang et al 2007;Huang et al 2008;Barz 2009), this effect has been neglected by assuming the complete neutralization and zero space charge density in the electrostatic equation. The underlying assumption in all these studies is that the ion concentration of the buffer is (more than a thousand times) larger than the sample concentration so that there are enough ions to screen the sample molecule charges (Kassegne et al 2003;Karniadakis et al 2005).…”

“…In the former method, the particle charge-to-mass ratio is the most important factor determining the particle motion; while in the latter, the particle polarizability is the essential parameter (Zahn 2010). Dielectrophoretic transport of biomolecules has been extensively studied during the past years and is still a subject of interest in immunoassay system analyses (Sigurdson et al 2005;Feldman et al 2007;Yang et al 2007;Huang et al 2008). Although dielectrophoresis leads to larger driving forces and higher sensitivities, electrophoresis is still widely being used for its simplicity, as only a DC electric source is required.…”

Numerical simulation of a 2D electrothermal pump by lattice Boltzmann method on GPU

“…Hong et al investigated electrothermal flow in a microchannel and its effects such as the electrode size and material properties of the electrolyte solution and channel base material, and AC voltage and frequency [12]. Mixing and binding efficiency for the heterogeneous immune-sensors in microfluidic systems can be enhanced with electrothermal flow [14][15][16]. Feng et al [14] numerically studied mixing by electrothermal flow in a cavity and microchannel.…”

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

“…The procedure of numerical simulation for the electrothermal force was shown in many literatures 5,33 and our previous works. 45,46 Since our purpose in numerical simulation was to view the local vortex flow field and temperature field near the electrodes created by ETE, a simplified 3-D block including only two pair of microelectrodes in the ETE-QCM chip was adopted, as shown in Figure 3(a). The dimensions of the block are 1500 lm  500 lm  150 lm.…”