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Excitation of acoustic waves in a quartz disk has been instigated by exposing the piezoelectric substrate to the electromagnetic field of a planar spiral coil placed in close proximity to the disk. It is argued that reciprocally induced magnetic and electric fields lead to secondary electric fields which couple with the piezoelectric tensor. A comparison of acoustic resonance envelopes recorded in air and in electrolyte demonstrates that spurious acoustic modes are damped in the liquid medium, and that the dielectric properties at the device-solution interface contribute to the exciting electric field. In agreement with previous acoustic device work, increased viscosity of the surrounding fluid leads to a rise in damping which manifests itself in changes in sensor frequency, amplitude and quality factor. With respect to work at high frequencies it is possible to operate the device at as high a harmonic as the 75th, although at this level of frequency resonance begins to break down because of a significant reduction in acoustic Q value. Finally, the use of the system in the flow-injection mode has also been demonstrated through the on-line detection of the adsorption of the protein, neutravidin, to the device surface. The glycosylated parent molecule is very widely employed as a linker for the immobilization of biological macromolecules in bioanalytical chemistry.

Nanoscience promises to transform today's world in the same way that integrated semiconductor devices transformed the world of electronics and computation. In the post-genomic era, the greatest challenge is to make connections between the structures and functions of biomolecules at the nanometre-scale level in order to underpin the understanding of larger scale systems in the fields of human biology and physiology. To achieve this, instruments with new capabilities need to be researched and developed, with particular emphasis on new levels of sensitivity, precision and resolution for biomolecular analysis. This paper describes an instrument able to analyse structures that range from tenths of a nanometre (proteins, DNA) to micron-scale structures (living cells), which can be investigated non-destructively in their normal state and subsequently in chemical- or biochemical-modified conditions. The high-resolution scanning Kelvin nanoprobe (SKN) measures the work-function changes at molecular level, instigated by local charge reconfiguration due to translational motion of mobile charges, dipolar relaxation of bound charges, interfacial polarization and structural and conformational modifications. In addition to detecting surface electrical properties, the instrument offers, in parallel, the surface topographic image, with nanometre resolution. The instrument can also be used to investigate subtle work function/topography variations which occur in, for example, corrosion, contamination, adsorption and desorption of molecules, crystallographic studies, mechanical stress studies, surface photovoltaic studies, material science, biocompatibility studies, microelectronic characterization in semiconductor technology, oxide and thin films, surface processing and treatments, surfaces and interfaces characterization. This paper presents the design and development of the instrument, the basic principles of the method and the challenges involved to achieve nanometric resolution and sub-millivolt sensitivity, for both the topographic imaging of surface micromorphology and surface potential and work-function determination.

Kelvin and acoustic fields of high-frequency have been employed in the non-invasive investigation of immortalized hypothalamic neurons, in order to assess their response to different concentrations of specific drugs, toxins, a stress-reducing hormone and neurotrophic factors. In an analytical systems biology approach, this work constitutes a first study of living neuron cultures by scanning Kelvin nanoprobe (SKN) and thickness shear mode (TSM) acoustic wave techniques. N-38 hypothalamic mouse neurons were immobilized on the gold electrode of 9 MHz TSM acoustic wave devices and gold-coated slides for study by SKN. The neurons were exposed to the neurochemicals betaseron, forskolin, TCAP, and cerebrolysin. Signals were collected with the TSM in real-time mode, and with the SKN in scanning and real-time modes, as the drugs were applied at biologically significant concentrations. With the TSM, for all drugs, some frequency and resistance shifts were in the same direction, contrary to normal functioning for this type of instrument. Possible mechanisms are presented to explain this behaviour. An oscillatory signal with periodicity of approximately 2 min was observed for some neuron-coated surfaces, where the amplitude of these oscillations was altered upon application of certain neurotrophic factors. These two new techniques present novel and non-invasive electrodeless methods for detecting changes at the cellular level caused by a variety of neuroactive compounds, without killing or destroying the neurons.

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