Technology: Biological

Piezoelectric devices can be coated with biologically specific coatings such as antibodies, DNA, RNA, aptamers, and other molecules to produce biosensors for target analytes, also known as piezoelectric bioaffinity sensors. Piezoelectric biosensors have been widely used for laboratory based bioanalytical assays, including detection of viruses, bacteria, proteins, nucleic acids, and other molecules, and for the direct real-time monitoring of affinity interactions, including determination of the kinetic rate constants for the interactions [1]. Most piezoelectric biosensors utilize mass changes induced by formation of biocomplexes, although biosensors using changes in fluid viscosity and sensors responding to changes in electrical conductivity have also been investigated.

A wide range of bioreceptors have been bound to the surface of various piezoelectric devices for biosensor implementation, including antibodies, proteins, DNA and RNA, and numerous other molecules (see discussion below). Piezoelectric and acoustic devices such as quartz crystal microbalance (QCM) and surface acoustic wave (SAW) biosensors provide a simple and potentially very cost-effective alternative to more complex optical detection techniques, including surface plasmon resonance (SPR). Historically, these devices have been largely ignored by the biosensor community, possibly due to perceived low sensitivity. However, research results have demonstrated that piezoelectric bioaffinity sensors are a useful tool for the rapid and simple detection of bacteria, viruses, proteins, nucleic acids, and other biologically relevant targets, with sensitivities that can meet or exceed other detection approaches. For example, an antibody-based sandwich assay on a 9 MHz QCM was used for direct real-time detection of C. trachomatis with sensitivities superior to that of standard ELISA tests. The response time of this sensor was less than 10 minutes, and the approach successfully detected C. trachomatis in urine samples [2].

In addition to QCM devices, other piezoelectric biosensor devices exist that utilize different acoustic wave propagation modes, including shear horizontal surface acoustic waves (SH–SAW), and acoustic plate modes (APMs) [3 - 6]. It is well known that the higher operating frequency of these devices can provide substantial increases in sensitivity relative to bulk devices such as the QCM [3, 4]. For QCM devices, the crystal thickness sets the operating frequency, meaning that as operating frequency increases, the crystal substrates become thinner and more fragile. This limits traditional QCM devices to operating frequencies of 5-10 MHz. Operating frequencies for SH-SAW and APM devices are determined not by the crystal thickness, but by electrode periodicity, meaning that thicker, less fragile crystal substrates can be used. These devices can easily be fabricated to exhibit fundamental mode operation from 70 MHz to over 2 GHz. SH-SAW immuno-sensors operating at 345 MHz were shown to have a theoretical detection limit of ~33pg and a sensitivity of 110 kHz/(ng/mm2) [7, 8]. Traditional SH-SAW and APM devices on standard wafer thicknesses, however, do not demonstrate the best possible sensitivity for a given device operating frequency, and various means of localizing the acoustic wave to the surface of the device have been investigated to provide enhanced device sensitivity. Surface transverse waves (STWs) can be formed when waveguiding structures trap the propagating wave to the surface. Use of a layer with lower shear acoustic speed than the substrate will result in Love waves, which are also trapped at the interface between the substrate and the layer [3, 4].

The primary impediment to the widespread commercial use of existing SAW-based biosensors is the requirement for a sample cell to control fluid flow onto the surface of the device while avoiding interference with the propagation of the acoustic wave. Various configurations have been used to encapsulate and protect device electrodes while controlling flow of the fluid sample. Silicone has been used to encapsulate transducers [9], or protective layers such as SiO2 have been deposited over entire devices [10]. APM devices benefit from the separation of the electrodes, which are on one side of the device, from the liquid sample which is on the reverse side of the device. Traditional APM devices utilize a liquid flow cell attached to the surface of the die opposite that with the electrodes [11]. For both SAW and APM devices, relatively complex packaging has been required to allow both electrical contacts and fluid handling, with features such as spring loaded electrical contacts and rubber seals to ensure liquid tight properties for the fluid cell [12].

Bibliography.

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