Characterization of gold electrodes in phosphate buffered saline solution by impedance and noise measurements for biological applications.

Impedance spectroscopy and noise measurements have been used to study gold electrodes of three different surface areas in phosphate buffered saline (PBS) solution. The gold-PBS solution interface can be modeled by a charge transfer resistance in parallel with an interfacial constant phase element (CPE) which are in series with the solution resistance. The voltage noise fluctuations were analyzed using the fast Fourier transform (FFT) method. It is found that the voltage noise power is characterized by a 1/f(alpha) spectrum in the low frequency range. The value of alpha is observed to be double that of the CPE coefficient beta. The authors suggest a link between the interface impedance and the measured noise.

Fabrication of impedimetric sensors for label-free point-of-care immunoassay cardiac marker systems, with passive microfluidic delivery.

Miniaturised point-of-care cardiac marker sensors are being developed, based on impedimetric sensing of cardiac enzyme capture by an antibody layer immobilised on a planar gold electrode sensor. Gold/Ti-on-glass substrates have been used, in a 2 electrode configuration, with antibodies immobilised on the working electrode. Microfluidic structures have been fabricated by a CO2 laser, in 25 mum thick pressure sensitive adhesive (PSA), on a PMMA lid, and the structure bonded on top of the planar sensor. Microfluidic blood/serum delivery has been investigated using a visualisation dye. Some flow problems are observed if the sensor is exposed to air for several days, suggesting that flow channel nanopillars and hermetic encapsulation may be required to guarantee flow properties in commercially produced modules. Work is ongoing to characterise the impedimetric signal changes for myoglobin capture by antimyoglobin, using these sensors. Fifty micron thick PSA, incorporating a robust spacer layer, will be used to give better definition of channel walls.

An impedimetric sensor for monitoring the growth of Staphylococcus epidermidis.

There is a need for accurate, reliable methods of detecting bacteria for a range of applications. One organism that is commonly found in urinary catheter infections is Staphylococcus epidermidis. Current methods to determine the presence of an infection require the removal of catheters. An alternative approach may be the use of in vivo sensing for bacterial/biofilm detection. This work investigates electrical impedance spectroscopy to detect the growth of Staphylococcus epidermidis RP62A on gold electrodes fabricated on a flexible substrate. Impedance spectra measured during biofilm formation on the electrode surface showed an increase in charge transfer resistance (RCT) with time.

Wearable and implantable monitoring systems: 10 years experience at University of Ulster.

Over the past 10 years or more, NIBEC and, more recently, Sensor Technology and Devices Ltd have been at the forefront of developments in sensor-related technologies which underpin a wide range of monitoring systems presently commercialised by leading multinationals. Systems developed/ commercialised include astronaut-monitoring arrays, cardiac mapping harnesses, ECG electrodes, Telemedicine systems and implant sensor arrays. This paper presents the main developments in this area and discusses outstanding issues for future research.

Sauer's non-linear voltage division.

The non-linearity of the electrode-tissue interface impedance gives rise to harmonics and thus degrades the accuracy of impedance measurements. Also, electrodes are often driven into the non-linear range of their polarisation impedance. This is particularly true in clinical applications. Techniques to correct for electrode effects are usually based on linear electrode impedance data. However, these data can be very different from the non-linear values needed. Non-linear electrode data suggested a model based on simple assumptions. It is useful in predicting the frequency dependence of non-linear effects from linear properties. Sauer's treatment is a first attempt to provide a more general and rigorous basis for modelling the non-linear state. The paper reports Sauer's treatment of the non-linear case and points out its limitations. The paper considers Sauer's treatment of a series arrangement of two impedances. The tissue impedance is represented by a linear voltage-current characteristic. The interface impedance is represented by a Volterra expansion. The response of this network to periodic signals is calculated up to the second-order term of the series expansion. The resultant, time-dependent current is found to contain a DC term (rectification), as well as frequency-dependent terms. Sauer's treatment assumes a voltage clamp across the impedances and neglects higher-order terms in the series expansion. As a consequence, it fails adequately to represent some experimentally observed phenomena. It is therefore suggested that Sauer's expressions for the voltage divider should be combined with the non-linear treatments previously published by the co-authors. Although Sauer's work on the non-linear voltage divider was originally applied to the study of the non-linear behaviour of the electrode-electrolyte interface and biological tissues, it is stressed, however, that the work is applicable to a wide range of research areas.

Harmonic analysis of low-frequency bioelectrode behavior.

This paper concerns the modeling and interpretation of harmonics observed as a result of the nonlinear electrical properties of biomedical electrode/electrolyte interfaces. The higher order harmonics have been calculated assuming that the nonlinearity of the interfacial impedance is dominated at low frequencies by the nonlinear faradaic charge transfer resistance. The harmonic distribution in the output signal is compared between 1) the author's theoretical model based on the Butler-Volmer equation and 2) Schwan's empirical model and results. The influence of different parameters such as the number of electrons involved in the faradaic reaction and the transfer coefficient was investigated in order to physically interpret the experimental results. A good agreement was found between the authors' model and some of the experimental data previously reported in the literature. Further, potentially productive areas of research have been identified.

A comparison of amperometric screen-printed, carbon electrodes and their application to the analysis of phenolic compounds present in beers.

In this paper a comparison between three commercially-available, screen-printable graphite inks for the construction of phenolic biosensors is made. The enzyme tyrosinase was immobilised within a polymer matrix and the substrate catechol was used to characterise the bio-electroanalytical response of each electrode. Biosensors fabricated from Gwent graphite inks exhibited the greatest sensitivity (5740 mA mol cm(-2)) compared to Dupont and Acheson graphite-based inks. This difference in sensitivity was attributed to a combination of a larger electroactive surface area, and thus a greater number of immobilised enzyme molecules. However, the dynamic range was considerably smaller (0.025-14 muM) indicating that the enzyme molecules were easily accessible to the substrate catechol. The surface properties of the biosensors were characterised using ac impedance, which indicated that the presence of the polymer on the electrode surface not only increased the charge-transfer kinetics of the three biosensors, but also increased the surface roughness of biosensors fabricated from Gwent inks. On the basis of these results Gwent graphite-based inks were used for analysis of phenolic compounds in lager beers by flow-injection analysis. The biosensor displayed favourable response characteristics, but cannot differentiate between the various phenolic compounds present in the samples. Nevertheless, the biosensor maybe suitable for indicating the phenolic status of beer or brew samples compared to time-consuming traditional methods, e.g. colorimetric or chromatographic methods.

Nonlinear transient response of electrode-electrolyte interfaces.

The voltage transient response, V(t), of the electrode-electrolyte interface is known to be nonlinear. It has been shown by Onaral and Schwan in 1983 that the DC limit current of linearity, IAL, is proportional to t-beta were beta is the fractional power dependence of the linear, short pulse duration impedance. We now seek to explain the physical phenomena underlying this observation. We present an equivalent circuit model of the interface and highlight the major source of the observed nonlinear behaviour. Using the equivalent circuit model and associated formulae, an expression for the limit current of linearity is derived and compared with that found experimentally by Onaral and Schwan. According to this theoretical model, a current of as little as 22 nA can be sufficient to drive an electrode system into nonlinear behaviour at longer pulse durations.

In vivo ac impedance spectroscopy of human skin. Theory and problems in monitoring of passive percutaneous drug delivery.

The use of impedance spectroscopy to evaluate transdermal drug delivery is discussed and new techniques and protocols are suggested to avoid or minimize potential problems. A novel multichannel impedance analyzer, exploiting the advantages of the "three-electrode" configuration, was employed to measure the effects of differing topically applied concentrations of the percutaneous local anesthetic amethocaine on the electrical properties of the treated skin sites. Each measured impedance spectrum was modeled by an equivalent circuit consisting of a resistor in series with the parallel combination of a pseudocapacitance and a resistor. Due to differences in skin sites and to the finite times taken to apply each electrode, it was difficult to satisfactorily compare and contrast the results obtained from adjacent skin sites. Normalization of data highlighted differences in relative impedance changes and aided the meaningful comparison of treated skin sites.

Factors affecting electrode-gel-skin interface impedance in electrical impedance tomography.

The magnitude, mismatch and temporal variations of the electrode-gel-skin interface impedance can cause problems in electrical impedance tomography (EIT) measurement. It is shown that at the high frequencies generally encountered in EIT the capacitive properties of the electrode interface, and especially those of the skin, are of primary importance. A wide range of techniques are reviewed that could possibly be used to minimise these problems. These techniques include the use of skin preparation, penetration enhancers, temperature and electrical impulses. Although several of these techniques appear very attractive, they are not without serious potential drawbacks. A combination of some of these techniques may well hold the key to success.

Tissue impedance: a historical overview.

Over the past 150 years the study of the electrical properties of various biological tissues has been undertaken by researchers from a wide variety of scientific backgrounds. This has, unfortunately, led to the existing range of confusing and misunderstood terminology/concepts. Some of the most important are presented and explained.

The detection of the onset of electrode-electrolyte interface impedance nonlinearity: a theoretical study.

The equivalent series resistance and reactance of the electrode-electrolyte interface impedance have both been used to detect the onset of signal amplitude induced nonlinearity. Using a theoretical model, it is shown that the choice of the most sensitive indicator depends on the phase angle of the "polarization" impedance and on the applied frequency.

Physical interpretation of Schwan's limit voltage of linearity.

The electrode/electrolyte interface impedance can be represented by the parallel combination of a non-faradaic pseudocapacitance and a faradaic, charge transfer resistance. The non-linearity of the overall electrode/electrolyte interface impedance is largely due to that of the faradaic resistance which is derived from the Butler-Volmer equation. As the charge transfer resistance dominates the interface impedance at low frequencies, it is in this region that non-linearities are first observed. The voltage limit of linearity has been investigated and found to increase gradually for higher frequencies. Although relatively linear compared with the charge transfer resistance, the non-faradaic impedance becomes non-linear at large applied voltage amplitudes and dominates the high-frequency non-linear behaviour of the overall interface impedance. Mid-frequencies are affected by a combination of the faradaic and non-faradaic non-linearities.

Portable cardiac mapping assessment of acute ischaemic injury.

A portable cardiac mapping system is used to improve the accuracy of diagnosis of acute ischaemic injury outside hospital. Patients presenting chest pain suggestive of myocardial infarction (MI) were mapped by attendant medical personnel operating from a mobile coronary unit. These first MI maps were compared against average normal maps using QRS and ST-T isointegral values. Discriminant function analysis performed on the parameters achieved a sensitivity of 90% and a specificity of 96%.

A high frequency electrical impedance tomograph using distributed parallel input channels.

Electrical Impedance Tomography (EIT) is an imaging technique based on multiple impedance measurements using electronically multiplexed surface electrodes. The present study describes an EIT prototype tomograph which uses two frequencies of applied signal: 31.25 kHz (within the frequency range originally used in early EIT studies) and 250 kHz. The use of the latter frequency was made possible as a result of several technical innovations including the use of separate groups of electrodes for current injection and for differential voltage measurement and the use of parallel input channels distributed around the object. In vitro images were successfully obtained using the system at the above two frequencies. It is concluded from this study that Electrical Impedance Tomography can be used at sufficiently high frequencies to enable bio-electrical tissue characterisation.

A physical interpretation of Schwan's limit current of linearity.

In this the second of a series of papers on the nonlinearity of the electrode-electrolyte interface impedance, the wealth of experimental observations which exists in the literature on AC impedance nonlinearity is physically interpreted. The interface impedance is well represented by the parallel combination of a constant phase angle impedance and a charge transfer resistance. The charge transfer resistance is the major source of the observed nonlinearities. As a result, the current limit of linearity, iL, increases with frequency such that iL is proportional to omega beta. The series resistance, Rs, of the interface impedance initially increases with applied signal amplitude, reaches a maximum and then decreases. The series reactance, Xs, decreases monotonically with signal amplitude.

Optimal electrolytic chloriding of silver ink electrodes for use in electrical impedance tomography.

The electrode-electrolyte interface impedance may be simplistically modelled by an equivalent circuit comprising a resistance, RTOTAL, in series with an empirical, constant phase angle impedance, ZCPA. This pseudo-capacitance can be thought of as representing empirically the non-faradaic, double layer capacitance in the presence of specific adsorption and surface roughness effects. RTOTAL is the sum of the lead and electrolyte resistances. Depositing a thin layer of silver chloride on silver electrodes can yield improved electrical performance characteristics (potential and impedance) when used in conjunction with a chloride gel. An electrolytically deposited AgCl layer tends to have a rough surface profile thus leading to an increase in the effective interface area. This gives rise to a decrease in RTOTAL and ZCPA, both of which are desirable. Unfortunately AgCl is a relatively poor conductor. Increasing layer thickness causes RTOTAL to increase, thus adversely affecting the inter-electrode impedance at high frequencies. Electrode systems for use in electrical impedance tomography therefore require only relatively thin layers of AgCl.