Covalent enzyme immobilization on paramagnetic polyacrolein beads.

An optimized procedure of covalent glucose oxidase, urease, Bacillus subtilis alpha-amylase and Bacillus licheniformis alpha-amylase immobilization on paramagnetic, non-porous, polyacrolein beads is presented. The resulting insolubilized enzymes can be employed for extended periods of time without loss of activity. The conditions were optimized for maximizing the activity of the linked enzyme. Coated beads bearing up to 15 micrograms active enzyme/mg(beads) were obtained on reproducible basis. The paramagnetic feature of the particles facilitates the enzyme handling. In the magnetic field, the enzyme separation is fast and complete. Thus, the paramagnetic beads represent an excellent carrier for immobilized enzymes.

Design optimisation of planar electrolytic conductivity sensors.

Planar conductivity sensors are the subject of increasing interest as basic transducers for biosensors. The high degree of control of the performance characteristics undoubtedly forms an important argument in favour of conductivity-based sensing. The paper provides an outline of the design rules to be followed if an optimal design of a planar conductivity cell is required. Based on a simplified model, it is shown that the required accuracy establishes a lower limit to the overall sensor dimensions. This lower limit is expressed as a minimum longitudinal path length necessary to obtain the desired accuracy. Given an available area, the optimum ratio of electrode-width over inter-electrode spacing for a basic two-electrode structure is shown to be close to unity. Furthermore, it is shown that the decomposition of the two electrodes into an interdigitated structure decreases the accuracy of the device if all other parameters are considered constant. If the sensing region has to be limited to within a thin sensitive layer, the splitting is proposed of one of the electrodes into a compound electrode. The optimum lay-out of this compound structure is calculated as a function of the layer thickness.

Continuous monitoring of the spent dialysate urea level using a disposable biosensor. Clinical evaluation.

The first real-time, online measurements obtained using a screen-printed planar sensor to continually monitor urea in the spent dialysate are described. Evaluation of the sensor performance in the real clinical situation involves an extensive comparison of pre and post dialysis characteristics. Steady-state response and calibration curves show excellent reproducibility (typically within 5%; maximum deviation, 15%). The real-time results show that the characteristics predicted from the predialysis characterization are preserved during and after the prolonged period of continuous contact with the dialysate without needing recalibration. An operational stability of more than 10 hours of continuous use has been observed. Stability including intermittent wet-storage was found to be more than 5 days. Zero-baseline stability greater than 0.2 mmol/l (1.2 Og/dl) during the 4 hr treatment period and a resolution of 0.2 mmol/l were achieved, with a full-scale range of 15 mmol/l (90 mg/dl). A response time of less than 3 minutes allows dialysate urea levels to be monitored as a function of dialysis parameters such as varying blood flow. Parallel analysis of dialysate samples taken at 15 min intervals shows good correlation with the recorded data, although correspondence of the absolute values requires that the real-time data be rescaled. Because no degradation of the sensor performance was observed in vitro, this deviation can be explained only in terms of a dialysate based interference, probably caused by changes in pH and buffer.

Cough-induced electrostimulation in incontinence.

A new method for treatment of urinary stress incontinence is described. Through a vaginal plug the pelvic floor muscles receive a series of electric stimulations which are triggered by an increase of abdominal pressure, detected by an inbuilt pressure sensor. In this study the best parameters for the stimuli are determined during three successive coughs, which are the most common course of urine loss.

A disposable urea sensor for continuous monitoring of hemodialysis efficiency.

A new sensor for the on-line measurement of urea in the dialysate output is described. The sensor is based on a differential measurement of conductivity changes induced by the urease-catalyzed hydrolysis of urea. The use of screen printing for the batch-fabrication of the basic transducers results in cheap disposable devices. In addition, the sensor has been designed to fit into a standard male luer-adapter, and can be plugged directly into the dialysate line. The in vitro response is linear to urea concentrations exceeding 6620mM. A resolution of 20020 microM has been achieved with a baseline stability of 50 microM/hr. Interferences caused by fluctuations in the ionic strength and the consequent conductivity changes are effectively suppressed by the differential sensor pair. The efficiency of this suppression is expressed in a common mode rejection ratio of typically 40 to 50. Preliminary ex vivo results show the feasibility of the concept. The sensor principle is not restricted to urea but can be extended to other molecules of interest for hemodialysis monitoring, such as creatinine and L- and D-amino acids.

Electrical impedance tomography systems based on voltage drive.

At the ESAT-MICAS research facility in Leuven, several EIT systems have been designed and realised. The latest hardware set-up makes use of a PC to control the data collection and to reconstruct the images. A voltage drive strategy and no common-mode feedback are some of its specific characteristics. The function-generator produces signals with a frequency between 10 and 100 kHz, so multifrequency images can also be produced. Static images have already been obtained and (semi-)real time imaging is possible with our latest mark IV system. This system has 16 bit analogue-to-digital convertors and is capable of taking 50 x 10(3) samples/s.

Adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average modelling.

The recording of the human gastric myoelectrical activity by means of cutaneous electrodes is called electrogastrography (EGG). It provides a noninvasive method of studying electrogastric behaviour. The normal frequency of the gastric signal is about 0.05 Hz. However, sudden changes of its frequency have been observed and are generally considered to be related to gastric motility disorders. Thus, spectral analysis, especially online spectral analysis, can serve as a valuable tool for practical purposes. The paper presents a new method of the adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average (ARMA) modelling. It is based on an adaptive ARMA filter and provides both time and frequency information of the signal. Its performance is investigated in comparison with the conventional FFT-based periodogram method. Its properties in tracking time-varying instantaneous frequencies are shown. Its applications to the running spectral analysis of cutaneous electrogastric signals are presented. The proposed adaptive ARMA spectral analysis method is easy to implement and is efficient in computations. The results presented in the paper show that this new method provides a better performance and is very useful for the online monitoring of cutaneous electrogastric signals.

Comparison of SVD methods to extract the foetal electrocardiogram from cutaneous electrode signals.

The paper presents and compares three methods making use of the singular value decomposition (SVD) of a matrix to extract the foetal electrocardiogram (FECG) from cutaneously recorded electrode signals. The first method constructs a set of orthogonal foetal signals (the so-called principal foetal signals) from the recordings, but needs electrode positions far from the foetal heart, in addition to the abdominal electrodes that pick up a mixture of maternal and foetal electrocardiogram. An online adaptive algorithm has been developed such that a real-time implementation becomes feasible. The second method is a new online approach to a technique presented by van Oosterom. Although this method has some important drawbacks and is suboptimal as far as foetal signal-to-noise ratio is concerned, it is still very useful when only a foetal trigger is required, as the signal obtained is not a complete FECG. Finally, a third method is proposed, based on the generalised SVD and interpreted with the new concept of oriented signal-to-signal ratio. An online version is also presented for this method and some results are shown.

Multichannel adaptive enhancement of the electrogastrogram.

The electrogastric signal can be measured cutaneously on the abdomen. This is attractive because it is harmless to patients or volunteers. However, the poor quality of the cutaneous measurements necessitates signal enhancements. Hence, in this paper, an adaptive multichannel signal enhancing system is proposed. The mu-vector least mean square (LMS) algorithm is applied to adjust the weights of the adaptive filters in the system. The detailed description and the performance analysis of the system is given in the paper. Applying the proposed system, the respiratory artifact, the electrode-skin noise, some of motion artifacts, and the electrocardiography (ECG) can be efficiently reduced while the characteristics of the relevant gastric signal is less affected.

Observation of the propagation direction of human electrogastric activity from cutaneous recordings.

Electrogastric signals have been successfully measured both intraluminally and cutaneously. Although it has been claimed by several researchers that the propagation direction of the electrogastric activities cannot be observed from cutaneous recordings, it is the aim of the paper to show that it is feasible. The reason why the propagation direction has never been observed from cutaneous recordings is that the reported methods for the abdominal measurements are not adequate. In the paper it is pointed out that the stomach should be localised before the measurement and the electrodes should be attached along the longitudinal axis of the stomach.

Description of a real-time system to extract the fetal electrocardiogram.

An overview is given of the FEMME-project (Fetal Electrocardiogram Measuring Method and Equipment). The project started in 1981 and is, at the moment, close to producing a prototype personal computer-based system. This records simultaneously a number of cutaneous potential signals and derives from this set one or more maternal electrocardiogram-free fetal heart signals, by combining linearly the recorded signals. An on-line adaptive algorithm based on the Singular Value Decomposition (SVD) has been designed to compute the coefficients in these linear combinations. This algorithm will be implemented on a DSP board that can be plugged into the real-time recording system. The system will be very useful in studies of the fetal electrocardiogram during pregnancy, but also in all other studies such as fetal heart rate variability, fetal movements, etc., where a precise trigger of the electrical signal from the fetal heart is required.

The Internal Human Conditioning System: a multipurpose programmable biomedical system.

A proposed general-purpose implantable biomedical system is described. This Internal Human Conditioning System (IHCS) is capable of measuring biomedical data of various kinds on a number of independent input channels. The number and specifications of these channels are software selectable by means of a low-power microprocessor. The system is also equipped with different programmable stimulation devices. These stimulators can deliver a programmable waveform in order to stimulate a specific muscle or to carry out an impedance measurement. The on-board eight bit microprocessor is used for communication with the outside world, by means of a serial link. The processor used is the 68HC11 from Motorola. By extensive use of the processor's 'sleep' mode and by switching off all unnecessary electronics, the amount of power consumed is drastically reduced. At present, a two-channel input chip and a programmable stimulator chip have been developed so that a complete system can be produced. For the sake of illustration, some realized and possible future applications are discussed.

Adaptive method for cancellation of respiratory artefact in electrogastric measurements.

Electrogastric measurements are useful for medical research and in clinical diagnosis. The measurements, however, contain very heavy respiratory artefact. Existing conventional frequency-domain filters cannot be used because of the possible overlap of the frequencies of the gastric signals and respiratory artefact. In the paper, the methods of measuring cutaneous and intraluminal gastric signals and reference respiratory signals are described. An adaptive cancellation technique is developed, which is simple and easy to implement for online processing. It is proved by experiments to be very efficient, i.e. the respiratory artefact can be completely cancelled, while the gastric signal component is not affected. Other possible applications in biomedical signal analysis are also discussed.

An adaptive on-line method for the extraction of the complete fetal electrocardiogram from cutaneous multilead recordings.

The detection of a fetal electrocardiogram (FECG) is described to be a so-called inverse problem. A geometric interpretation of such a problem is presented. It can be solved by determining the weights to be used in one or more weighted sums of measurement signals. A novel method is presented to determine these weights. Theoretical and experimental evidence is given that this method has the following attractive properties. Application of the method results in one or more FECG signals, free of maternal ECG (MECG) which are at the same time maximal with respect to noise. It is shown that one FECG signal does not always suffice to describe the observed electrical heart activity in a set of cutaneous electrodes, equivalently to the adult ECG (see figure 7). It is explained and experimentally verified that the application of three thoracic signals is useful to guarantee the suppression of the MECG. The positions of the abdominal electrodes then determine the obtained FECG to noise ratio, and will have no influence on the degree of MECG suppression (see figure 6). It is expected that a total of about eight measurement signals are sufficient in most cases. The method is simple to apply by medical personnel, and after a transient of about 1 s the signals with the mentioned properties are obtained (see figure 5). Further on, the weights are allowed to change in order to adapt automatically to sudden changes in the measurement signal properties (see figure 6). These may occur e. g. due to fetal movement. Application of the method requires no human interpretation or decision in order to obtain the claimed properties.

The UIA-KUL cochlear implant. Goals and status praesens.

The authors describe the characteristics and specific advantages of their 8 channel bipolar intrascalar stimulator, its main asset being flexibility. They emphasize the need for caution in the use of cochlear implants in children.

Status praesens: cochlear implant. UIA-KULeuven-Forelec.

The authors review some basic anatomy and physiology of the auditory system as an introduction to the principles of cochlear implantation. A detailed description of the UIA-KUL-Forelec implant (LAURA) is given.