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Identifying the Removal Mechanism of Fouling Proteins in a Surface Acoustic Wave Biosensor: a Numerical Study and Comparison to Experiments

Subramanian K.R.S. Sankaranarayanan1, Stefan Cular2, and Venkat Bhethanabotla2. (1) School of Engineering and Applied Sciences, Harvard University, 9 & 15 Oxford Street, Cambridge, MA 02138, (2) Department of Chemical Engineering, University of South Florida, 4202 East Fowler Ave., ENB 118, Tampa, FL 33620

All transducer devices used for biological species detection suffer from fouling that result from binding of non-specific protein molecules to the device surface. Non-specific binding dramatically reduces the sensitivity and selectivity of biosensors [1-2]. Our experimental study indicates that the acoustic streaming phenomenon i.e. fluid motion induced from high intensity sound waves can be used to remove these non-specifically bound proteins to allow reuse of SAW devices (Fig. 1). A finite element fluid solid interaction (FE-FSI) model of acoustic streaming phenomenon resulting from the interaction of surface acoustic waves (Rayleigh mode) with liquid loading is developed in this work (Fig. 2). Parameters studied using the FE-FSI model include voltage intensity, device frequency, fluid viscosity and density. The transient solutions generated from the model were used to predict trends in acoustic streaming velocity. The generated streaming velocity fields are then utilized to predict the various adhesive and removal forces experienced by the specific and non-specifically bound protein molecules located at various regions along the SAW biosensor delay path. Insights into the dominant mechanism responsible for efficient removal of non-specifically bound proteins can be obtained from the estimates of various forces predicted using perturbation methods and from the trends in the streaming velocity fields. For the sake of simplicity, the protein molecules are modeled as spherical shaped particles. The different SAW-induced forces which include linear forces such as added mass, drag, lift, and Basset forces and nonlinear ones due to radiation pressure, and drag exerted by acoustic streaming-are discussed and their magnitudes are evaluated for various particle sizes. The combined effect of the various interaction (adhesive and removal) forces is utilized to gain insights into the non-specifically bound protein removal mechanisms. The principal adhesion forces such as van der Waals forces and electrical double layer forces are used to model the interaction of the specific and non-specifically bound proteins to the biosensor surface. The forces responsible for removal of particles are mainly characterized as the direct SAW forces or the acoustic radiation forces as well as the lift and the drag forces that result from the mean velocity field in the fluid. The streaming velocity field (Fig. 3) computed using the FE-FSI model is utilized to estimate the fluid induced drag and lift forces for a range of operating conditions and fluid properties. Comparison of the various removal forces to the adhesive forces that bind the specific and non-specific proteins is used to estimate the removal efficiency along the SAW biosensor delay-line and optimize conditions which can enhance the same. Simulation results predict strong coupling of ultrasonic surface waves on the piezoelectric substrate with the thin liquid layer causing wave mode conversion from Rayleigh to leaky SAW, which leads to acoustic-streaming as shown in Figs. 2 and 3. Streaming velocity fields were studied for a range of input parameters. The streaming velocity variation with applied input voltage is shown in Fig. 4(a). The induced streaming velocities typically vary from 1 Ám/s to 1 cm/s with the exact values dictated by the device operating conditions as well as fluid properties. The generated streaming velocities were used to compute the various adhesive and removal forces involved. Our study indicates that the SAW body force overcomes the adhesive forces of the fouling proteins to the device surface and the fluid-induced drag and lift forces prevent its re-attachment. The streaming velocity fields computed using the finite-element models in conjunction with the proposed mechanism were used to identify the conditions leading to improved removal efficiency. In particular, the results of our numerical analysis show that higher amplitude and high frequency surface acoustic waves can clean biosensor surfaces most effectively in media with fluid properties similar to those of water, i.e. lower viscosity and density, when (1) the SAW wavelength can be made comparable to the particle radius to promote effective acoustic-particle interaction; (2) the viscous boundary layer is thin and (3) both the non-linear acoustic streaming and radiation pressure forces exceed typical adhesion forces which is true for MHz frequencies. Based on the above analyses, possible mechanisms of non-specifically bound protein removal as shown in Fig. 4(b) are discussed and interpreted in terms of the experimental observations of SAW biosensor surface cleaning. Predictions of the model are in good agreement with those of simple analytical theories as well as the experimentally observed trends of non-specific protein removal in typical SAW biosensing operation.