In the early days of electronic communication-as a result of the limited number of quartz resonators available-frequency adjustment was accomplished by a pencil mark depositing a foreign mass layer on the crystal. In 1959, Sauerbrey showed that the shift in resonance frequency of thickness-shear-mode resonators is proportional to the deposited mass. This was the starting point for the development of a new generation of piezoelectric mass-sensitive devices. However, it was the development of new powerful oscillator circuits that were capable of operating thickness shear mode resonators in fluids that enabled this technique to be introduced into bioanalytic applications. In the last decade adsorption of biomolecules on functionalized surfaces turned in to one of the paramount applications of piezoelectric transducers. These applications include the study of the interaction of DNA and RNA with complementary strands, specific recognition of protein ligands by immobilized receptors, the detection of virus capsids, bacteria, mammalian cells, and last but not least the development of complete immunosensors. Piezoelectric transducers allow a label-free detection of molecules; they are more than mere mass sensors since the sensor response is also influenced by interfacial phenomena, viscoelastic properties of the adhered biomaterial, surface charges of adsorbed molecules, and surface roughness. These new insights have recently been used to investigate the adhesion of cells, liposomes, and proteins onto surfaces, thus allowing the determination of the morphological changes of cells as a response to pharmacological substances and changes in the water content of biopolymers without employing labor-intense techniques. However, the future will show whether the quartz-crystal microbalance will assert itself against established label-free sensor devices such as surface plasmon resonance spectroscopy and interferometry.

Piezoelectric Mass‐Sensing Devices as Biosensors—An Alternative to Optical Biosensors?

Advantages and Challenges of Relaxor-PbTiO3 Ferroelectric Crystals for Electroacoustic Transducers- A Review.

This review paper focuses on interdigital electrodes-a geometric structure encountered in a wide variety of sensor and transducer designs. Physical and chemical principles behind the operation of these devices vary so much across different fields of science and technology that the common features present in all devices are often overlooked. This paper attempts to bring under one umbrella capacitive, inductive, dielectric, piezoacoustic, chemical, biological, and microelectromechanical interdigital sensors and transducers. The paper also provides historical perspective, discusses fabrication techniques, modeling of sensor parameters, application examples, and directions of future research.

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Interdigital sensors and transducers

The most significant advance in this field in the past year has been the demonstration that single-crystal langasite, La3Ga5SiO14, can be used, at least at high frequencies, at temperatures up to 1000 degrees C. New evidence suggests that domain-wall contributions to the piezoelectric response of bismuth-titanate-based high temperature ferroelectric ceramics may be controlled using suitably chosen dopants. Modified bismuth titanate compositions are interesting for sensor applications in the medium temperature range (up to 500 degrees C).

Materials for high temperature piezoelectric transducers

A review of sensors based on piezoelectric crystal resonators is presented. The survey focuses on the fundamental resonator modes rather than on the variety of surrounding support configurations in special sensor applications. First, the general properties of vibrating crystal sensors and their inherent superiority are described. The sensor concepts utilizing either homogeneous resonators with temperature and pressure (stress) as primary measurants or composite resonators with areal mass density and viscoelastic properties of the 'foreign' layer as primary measurands are discriminated. A comparison between bulk acoustic wave (BAW) and surface acoustic wave (SAW) resonators with respect to their primary sensitivity functions and principal capabilities for sensor applications is given and the importance of recent investigations on Lamb wave and horizontal polarized shear wave (HPLW) interdigital transducer (IDT) resonators is acknowledged. The importance of mode purity for high dynamic range sensors based on resonators and some aspects of the demand on specialized electronics are emphasized. The present state of established sensors based on primary sensitivities, e.g., quartz-crystal thermometers, pressure transducers, thin-film thickness and deposition-rate monitors, viscoelastic layer analysers (crystal/liquid composite resonators) is reviewed. A selection of the most promising recently investigated vibrating crystal sensors utilizing indirect sensitivities is described, including the wide field of analyte-selective coatings and resonator-based immunosensors or immunoassays. Finally, the potential of alternative piezoelectric materials for future sensor developments is briefly discussed.

Sensors based on piezoelectric resonators

A resonant ultrasonic field is applied to a suspension of micron size particles. The nodal planes of the sound field are slightly inclined to the main fluid flow. Since the acoustic forces cause the particles travelling along the planes, the particles are deflected from the fluid flow. An enriched suspension and the cleaned fluid can be obtained at different outlets. With the described resonator and 40 micron Polystyrene particles a separation efficiency higher than 80% was achieved.

Separation of Suspended Particles by use of the Inclined Resonator Concept

A layered piezoelectric resonator is introduced, that works as a cell retending filter in bioreactor flow loops. The resonator comprises two chambers; the first (passive volume) contains the cooling liquid, the second (active volume) the cell suspension. A separation efficiency of 99% has been achieved. The influence of the ultrasonic field on hybridoma cell viability was determined for three different cell cultures (R03 Virgil, 2F5, 1B1) up to ultrasonic field energy densities of 60 J/m3.

Trapping of Suspended Biological Particles by use of Ultrasonic Resonance Fields

An acoustic resonator was used to generate an ultrasonic standing wave field within a suspension of hybridoma cells. Acoustically induced aggregation and increased cell sedimentation rates were observed. Exposure of cells to ultrasonic resonance fields did not influence viability, growth rate, glucose consumption and antibody productivity. This paper demonstrates the potential of utilizing acoustic resonance separation methods in bioprocessing applications. Parameters investigated include time of ultrasound exposure, power level and cell concentration.

Aggregation and Separation of Hybridoma Cells by Ultrasonic Resonance Fields - Eifect on Viability, Growth Rate and Productivity.

Ultrasonic standing waves have been used for the separation of suspended particles, such as animal cells (Kilburn et al., 1989). This technology can be used for cell retention within the fermenter for high density cell culture or as cell removal step in downstream processing. Devices for bench scale applications have been developed and evaluated in experimental set-ups and on laboratory fermenters (Trampler et al., Doblhoff et al., 1994). To scale-up this promising technology for industrial processes, a number of criteria, such as aseptic and hygienic design, steam sterilisability, sufficient flow rates and separation efficiency have to be taken into account. In this paper we will discuss the theoretic limitations of different resonator designs and will describe experimental results with a new type of resonator with an internal cooling loop. The modular, aseptic device is mounted on top of the fermentation equipment and can be steam sterilised in-situ. High amplitudes necessary to achieve separation of animal cells cause thermal and acoustic flow within the separation chamber. The internal cooling loop reduces this temperature increase and thus disrupting forces, which would otherwise limit the achievable flow rate and separation efficiency.

Scale-Up of Ultrasonic Resonance Field Cell Separation Devices Used in Animal Cell Technology

During the past decade, several separation methodes based on the response of fine particles to ultrasonic standing wave fields have been developed. The forces acting on the particles depend beside other quantities on the energy density and therefore on the stored energy in the liquid. Since separation cells are mainly constructed as layered piezoelectric resonators, a model is presented, which can describe the frequency dependence of the quality factor of a composite piezoelectric resonator. In addition, using this model, the stored (elastic) energy in each of the layers related to the electric input power can be calculated.

Wolfgang Burger

Papers

Separation of Suspended Particles by use of the Inclined Resonator Concept

Trapping of Suspended Biological Particles by use of Ultrasonic Resonance Fields

Aggregation and Separation of Hybridoma Cells by Ultrasonic Resonance Fields - Eifect on Viability, Growth Rate and Productivity.

Scale-Up of Ultrasonic Resonance Field Cell Separation Devices Used in Animal Cell Technology

Frequency Dependence of the Acoustic Loss Distribution in Piezoceramic/Liquid Resonators