Direct comparison of the sensitivity of QCMs and AlN-based TFRs biosensors

We present the direct comparison of the performance of two gravimetric biosensors based on acoustic resonators, a quartz crystal microbalance and a high frequency AlN-based bulk acoustic wave film solidly mounted resonator (SMR). Both sensors are functionalized with streptavidin to detect the response to TBA29 aptamer biotin modified and different concentrations of thrombin. Experimental results reveal that both sensors succeed in detecting the targeted species, although SMRs show significantly greater sensitivity and a lower limit of detectio

Bacteria detection with high-frequency gravimetric biosensors based on AlN thin film resonators

Gravimetric sensors based on shear-mode resonators are suitable for in-liquid detection of biological species because their quality factors barely decrease during in-liquid operation. However, we have found that in the particular case of large ligands, such as bacteria, the transmission of the surface movement to them appears to be more efficient when movement takes place normal to the surface (longitudinal modes) instead of to parallel to it (shear modes). In this work, we succeeded in detecting bacteria with AlN-based bulk acoustic wave solidly mounted resonators operating in longitudinal modes at 2 GHz that we were unable to detect with shear mode

Gravimetric sensors operating at 1.1 GHz based on inclined c-axis ZnO grown on textured AI electrodes

Shear mode solidly mounted resonators (SMRs) are fabricated using an inclined c-axis ZnO grown on a rough Al electrode. The roughness of the Al surface is controlled by changing the substrate temperature during the deposition process to promote the growth of inclined ZnO microcrystals. The optimum substrate temperature to obtain homogeneously inclined c-axis grains in ZnO films is achieved by depositing Al at 100°C with a surface roughness ~9.2nm, which caused an inclination angle of ~25° of the ZnO c-axis with respect to the surface normal. Shear mode devices with quality-factors at resonance, Qr and effective electromechanical coupling factors, keff 2 , as high as 180 and 3.4% are respectively measured. Mass sensitivities, Sm of (4.9±0.1)kHz • cm2/ng and temperature coefficient of frequency (TCF) of ~−67ppm/K are obtained using this shear mode. The performance of the devices as viscosity sensors and biosensors is demonstrated by determining the frequency shifts of water-ethanol mixtures and detection of Rabbit immunoglobin G (IgG) whole molecule (H&L) respectively

Selection of aptamers to Neisseria meningitidis and Streptococcus pneumoniae surface specific proteins and affinity assay using thin film AIN resonators

The first steps in the development of an aptasensor for bacterial meningitis diagnosis in real time are described: slow off-rate modified aptamers (SOMAmer) selection, gravimetric sensor fabrication and functionalization of its active surface. SOMAmers polyclonal populations were generated to surface specific proteins PavA (S. pneumoniae) and FHbp (N. meningitidis) by systematic evolution of ligands by exponential enrichment method (SELEX). After eight rounds, they were tested by direct enzyme-linked oligonucleotide assays (ELONA) and by high frequency (1.4 GHz) gravimetric sensors based on thin film AlN resonators operating in shear mode. The sensing surface of the resonators was functionalized using a silane-glutaraldehyde based protocol and the binding of PavA and FHbp was measured in real time. The SOMAmers polyclonal populations showing the best ELONA results have been also tested using gravimetric sensors and the binding to the protein functionalized surface was measured in real time showing positive results. These first steps towards the development of an aptasensor for the targeted bacteria demonstrate the potential of the method for sensitive, rapid, and cost effective detection of bacterial meningitis

Rapid detection of pathogens using lyotropic liquid crystals

Lyotropic liquid crystals play an important role in many biological environments, such as micelles, liposomes, and phospholipid bilayers of cell membranes. In this work, we explore the performance of lyotropic liquid crystals as biosensors for macromolecules, proteins and whole microorganisms in hydrophilic media, i.e., the natural media where these specimens exist. The aim is to detect specific targets employing simple, unpowered sensors that can be used in the field, with minimum additional equipment. A number of different structures have been explored. The novelty in this work is the inclusion of a new optical effect, flow enhanced amplification, that allows for the semiquantitative detection of microscopic targets in lyotropic liquid crystal cells using the naked eye only

Integration and bio-functionalization of vertically aligned carbon nanotube forests on high frequency AlN gravimetric sensors

In this work, we grow different types of carbon nanotube (CNT) forests directly on AlNbased electroacoustic biosensors and study their functionalization efficiency. CNTs are used to increase the effective surface area of the sensor, pursuing a better sensitivity, without increasing the sensor capacitance. Here we use a general method for CNT bio-functionalization with specific receptors for targeted species. First, we make them hydrophilic. Next, we cover them with alternating polymers. Finally, we incubate their surface in an N-hydroxysuccinimide biotin solution. To study the functionalization homogeneity along the CNT length, Streptavidin conjugated with fluorescein isothiocyanate is used as the targeted species for confocal fluorescence microscopy characterization

Integration and bio-functionalization of vertically aligned carbon nanotube forests on high frequency AlN gravimetric sensors

In this work, we grow different types of carbon nanotube (CNT) forests directly on AlNbased electroacoustic biosensors and study their functionalization efficiency. CNTs are used to increase the effective surface area of the sensor, pursuing a better sensitivity, without increasing the sensor capacitance. Here we use a general method for CNT bio-functionalization with specific receptors for targeted species. First, we make them hydrophilic. Next, we cover them with alternating polymers. Finally, we incubate their surface in an N-hydroxysuccinimide biotin solution. To study the functionalization homogeneity along the CNT length, Streptavidin conjugated with fluorescein isothiocyanate is used as the targeted species for confocal fluorescence microscopy characterization

Gravimetric biosensor based on a 1.3 GHz AlN shear-mode solidly mounted resonator

We investigate the performance of solidly mounted resonators based on Ir/tilted-AlN/Ir piezoelectric stacks as biosensors. These films are deposited by varying the pressure, the cathode power and the tem- perature of a two-step process based on depositing (00 • 2)-tilted AlN active layers over an (10 • 3)-oriented AlN seed layer. To minimize the influence of the temperature coefficient of frequency on the stability of the biosensor, we use insulating acoustic mirrors made of layers of SiO 2 and amorphous TaO x with non- /4 thicknesses, which enables to reduce the TCF to − 14 ppm/ ◦ C. The mass loading of the resonators with SiO 2 thin films results in a sensitivity of 1800 kHz/pg • cm 2 . Surface functionalization consists on the binding of silane groups on plasma oxidized SiO 2 surfaces. After a glutaraldehyde link, streptavidin is bonded to the surface to receive biotinylated receptors for several species. We test thrombin-binding aptamer (TBA29 against thrombin, and IgG antibody against immunoglobulin). The sensors response to species of different molecular weight like TBA-29 (9.75 kDa) or IgG antibody (150 kDa) is monitored. Finally, we assess the response of the biosensors to different thrombin concentrations (ranging from 4 nM to 270 nM) on surfaces functionalized with the TBA29 aptamer

Integration of multilayered graphene on AlN based resonators as a functionalization platform for biosensors

In this communication we present the integration of graphene on the top electrode of solidly mounted resonators based on piezoelectric AlN thin films for gravimetric sensor applications. Because its particular chemical structure, graphene shows great potential as a bio-functionalization platform. However, in order to be commercially viable, direct deposition on the resonators is preferred to transfer techniques. The high temperatures involved in graphene chemical vapor deposition make this integration complex. Specially developed acoustic resonators, which can withstand high temperatures, combined with the use of multilayered top electrodes for AlN resonators, allow a successful integration of graphene. Finally, oxygen plasma treatments to optimize the creation of defects on the graphene layer can be used to firmly bond receptors on its surface