(647b) Hexagonal Surface Acoustic Wave Sensor for Multiple Biomarker Detection in Biosensing Applications

Summary Medical diagnostic applications of surface acoustic wave sensors, such as those in the detection of ovarian cancer, require the accurate detection of multiple disease biomarkers. Although biological sensors rely on specific and known antigen-antibody interactions for measurement, the non-specific interactions from biological species/proteins in the serum are undesirable as they lead to fouling of the device surface causing loss of specificity and sensitivity [1, 2]. In this work, we have developed a novel device configuration consisting of hexagonally oriented transducers on a Langasite substrate, which can be used for the detection of multiple biomarkers. We have utilized the piezoelectric crystal anisotropy which allows the propagation of waves with different characteristics along various directions, to achieve the objective of multiple species sensing and biofouling elimination in the same device. The differences in the binding constants of the different target biomarkers are exploited for differential detection of the same using mixed mode propagation in the off-axis direction. Three dimensional finite element models are utilized to identify and investigate the wave propagation characteristics along various crystal directions in a Langasite substrate, i.e (0, 22, 90), (0, 22, 30), and (0, 22, 150). Our results indicate that the on-axis (0, 22, 90) direction can be used for biosensing of a species due to shear horizontal wave propagation. The off-axis directions allow for mixed mode propagation, which induces acoustic streaming forces. The magnitude of these forces can be controlled using various design parameters to selectively and sequentially eliminate biomarkers due to differences in their binding energies such that a series of signals, corresponding to each biomarker, are obtained. Such a novel configuration allows for multiple biomarker detection, facilitating early and accurate detection of ovarian cancer. Computational details A three dimensional finite element model of a hexagonal SAW device based on Langasite substrate was developed (Figure 1). The dimensions of the piezoelectric substrate were 1600μm width x 1600μm propagation length x 200μm depth. The device was modeled with two port delay line consisting of two sets of IDTs along each of the three delay paths: the input IDTs and the output IDTs. The choice of delay path determines the nature of the propagating wave along the corresponding crystal cut and orientation. The frequency response and wave propagation characteristics are determined for the on-axis (0, 22, 90). Subsequently, the analysis is extended to the off-axis directions, which are rotated at angles of +60 and -60 with respect to the on-axis direction. The fingers were defined with periodicity of 40 μm and aperture width of 200 μm. The model was meshed with tetragonal solid elements with four degrees of freedom, three of them being the three translations and the fourth being the voltage. To optimize on the computation time while capturing the dynamics accurately, highest mesh densities were ensured near the device surface and the middle of the substrate. A total of 299, 000 nodes and 229, 000 elements were generated. An impulse response analysis was performed during 190 ns by applying an impulse voltage of 100 V at the input IDT and employing a time step of 0.95 ns to deduce the central frequency of the device along the various directions. Subsequently, an AC analysis was carried out, by applying a peak voltage of 2.5 V to the input IDTs and employing a time step of 1 ns, to investigate the nature of waves propagating in the different Euler directions on a Langasite based hexagonal SAW sensor. Results and discussion The frequency response of the device in the various Euler directions (Figure 2) indicates the propagation of acoustic waves with different characteristics and varying frequencies in the range of 59-78 MHz. The insertion loss was computed to be 6 dB, 16 dB, and 26 dB along (0, 22, 150), (0, 22, 90), and (0, 22, 30) directions, respectively. Our simulation results indicate that the on-axis shear horizontal component of displacement at the output IDT is an order of magnitude higher than the surface normal and longitudinal components indicative of shear horizontal wave motion thus making the (0, 22, 90) direction suitable for biosensing (Figure 3). Mixed wave propagation, with a prominent surface normal component, are found to propagate along the off-axis (0, 22, 30) and (0, 22, 150) directions. This corresponds to ~Rayleigh mode propagation along the off-axis directions which can be used to induce acoustic streaming and sequentially remove the biomarkers by exploiting differences in their binding constants. For various different power input along the off-axes, we show using our computational model that it is possible to induce varying magnitudes of acoustic streaming forces along the off-axes such that a series of signals, corresponding to the number of target biomarkers, are obtained. Thus, the integrated hexagonal transducer configuration allows for detection of multiple biomarkers in medical diagnostic applications of SAW sensors. Mutual interactions of these IDTs in this novel sensor configuration also lead to several interesting effects (Figure 4), the details of which will be presented at AIChE 2009 meeting.