Integrated Hybrid Sub-Aperture Beamforming and Time-Division Multiplexing for Massive Readout in Ultrasound Imaging.

This paper demonstrates hybrid sub-aperture beamforming (SAB) with time-division multiplexing (TDM) for massive interconnect reduction in ultrasound imaging systems. A single-chip front-end system prototype has been fabricated in 180-nm HV BCD technology that combines 5×1 SAB with 8×1 TDM to efficiently reduce the number of receive signal interconnects by a factor of 40. The system includes on-chip high-voltage (HV) pulsers capable of generating unipolar pulses up to 70 V in transmit (TX) mode. The receiver (RX) chain consists of a T/R switch, a variable-gain low-noise amplifier (VG-LNA) with 4-step gain control (15-32 dB) for time-gain compensation followed by a programmable switched-capacitor analog delay-and-sum beamformer. The proof-of-concept prototype operates at a 200-MHz clock frequency and the SAB provides 32-step fine delays with a maximum delay of 310 ns corresponding to better than λ/20 delay quantization at 5 MHz. With these specifications, the SAB is capable of beam steering from 0 ° to 45 ° for a 5-element subarray with 150-micron pitch ( λ/2), providing a near-ideal phased array imaging performance. The sub-aperture beamformer is followed by the TDM system where each of the 8 channels is sampled at a rate of 25 MS/s after an anti-aliasing bandpass filter. The full functionality of the prototype chip is validated through electrical and acoustic measurements on a 1-D capacitive micromachined ultrasonic transducer (CMUT) array designed for intracardiac echocardiography (ICE).

Isolated nerve palsy following insertion of a three-piece inflatable penile prosthesis.

Case report of a 57-year-old male who underwent insertion of an inflatable penile prosthesis due to erectile dysfunction, secondary to poorly controlled Type 2 diabetes and Peyronie's disease. The surgical procedure was uneventful and there were no immediate post-operative complications. During a routine follow-up, the patient described problems with the deflation of the implant and severe lower back and leg pain. Diagnostic MRI scans revealed reservoir migration, impingement of the obturator nerve and oedema in the adductor muscle group. The reservoir was initially repositioned, and later on removed due to ongoing symptoms.

High-Power Gallium Nitride HIFU Transmitter With Integrated Real-Time Current and Voltage Measurement.

High-Intensity Focused Ultrasound (HIFU) therapy provides a non-invasive technique with which to destroy cancerous tissue without using ionizing radiation. To drive large single-element High-Intensity Focused Ultrasound (HIFU) transducers, ultrasound transmitters capable of delivering high powers at relevant frequencies are required. The acoustic power delivered to a transducers focal region will determine the treated area, and due to safety concerns and intervening layers of attenuation, control of this output power is critical. A typical setup involves large inefficient linear power amplifiers to drive the transducer. Switched mode transmitters allow for a more compact drive system with higher efficiencies, with multi-level transmitters allowing control over the output power. Real-time monitoring of power delivered can avoid damage to the transducer and injury to patients due to over treatment, and allow for precise control over the output power. This study demonstrates a transformer-less, high power, switched mode transmit transmitter based on Gallium-Nitride (GaN) transistors that is capable of delivering peak powers up to 1.8 kW at up to 600 Vpp, while operating at frequencies from DC to 5 MHz. The design includes a 12 b 16 MHz floating Current/Voltage (IV) measurement circuit to allow real-time high-side monitoring of the power delivered to the transducer allowing use with multi-element transducers.

High-Frame-Rate Contrast-Enhanced Echocardiography Using Diverging Waves: 2-D Motion Estimation and Compensation.

Combining diverging ultrasound waves and microbubbles could improve contrast-enhanced echocardiography (CEE), by providing enhanced temporal resolution for cardiac function assessment over a large imaging field of view. However, current image formation techniques using coherent summation of echoes from multiple steered diverging waves (DWs) are susceptible to tissue and microbubble motion artifacts, resulting in poor image quality. In this study, we used correlation-based 2-D motion estimation to perform motion compensation for CEE using DWs. The accuracy of this motion estimation method was evaluated with Field II simulations. The root-mean-square velocity errors were 5.9% ± 0.2% and 19.5% ± 0.4% in the axial and lateral directions, when normalized to the maximum value of 62.8 cm/s which is comparable to the highest speed of blood flow in the left ventricle (LV). The effects of this method on image contrast ratio (CR) and contrast-to-noise ratio (CNR) were tested in vitro using a tissue mimicking rotating disk with a diameter of 10 cm. Compared against the control without motion compensation, a mean increase of 12 dB in CR and 7 dB in CNR were demonstrated when using this motion compensation method. The motion correction algorithm was tested in vivo on a CEE data set acquired with the Ultrasound Array Research Platform II performing coherent DW imaging. Improvement of the B-mode and contrast-mode image quality with cardiac motion and blood flow-induced microbubble motion was achieved. The results of motion estimation were further processed to interpret blood flow in the LV. This allowed for a triplex cardiac imaging technique, consisting of B mode, contrast mode, and 2-D vector flow imaging with a high frame rate of 250 Hz.

Supply-Inverted Bipolar Pulser and Tx/Rx Switch for CMUTs Above the Process Limit for High Pressure Pulse Generation.

A combined supply-inverted bipolar pulser and a Tx/Rx switch is proposed to drive capacitive micromachined ultrasonic transducers (CMUTs). The supply-inverted bipolar pulser adopts a bootstrap circuit combined with stacked transistors, which guarantees high voltage (HV) operation above the process limit without lowering device reliability. This circuit generates an output signal with a peak-to-peak voltage that is almost twice the supply level. It generates a bipolar pulse with only positive supply voltages. The Tx/Rx switch adopts a diode-bridge structure with the protection scheme dedicated to this proposed pulser. A proof- of-concept ASIC prototype has been implemented in 0.18-µm HV CMOS/DMOS technology with 60 V devices. Measurement results show that the proposed pulser can safely generate a bipolar pulse of -34.6 to 45 V, from a single 45 V supply voltage. The Tx/Rx switch blocks the HV bipolar pulse, resulting in less than 1.6 V at the input of the receiver. Acoustic measurements are performed connecting the pulser to CMUTs with 2 pF capacitance and 8 MHz center frequency. The variation of acoustic output pressures for different pulse shapes were simulated with the large signal CMUT model and compared with the experimental results for transmit pressure optimization. A potential implementation of the methods using MEMS fabrication methods is also described.

A Reduced-Wire ICE Catheter ASIC With Tx Beamforming and Rx Time-Division Multiplexing.

This paper presents a single chip reduced-wire active catheter application-specific integrated circuit (ASIC), equipped with programmable transmit (Tx) beamforming and receive (Rx) time-division multiplexing (TDM). The proposed front-end ASIC is designed for driving a 64-channel one-dimensional transducer array in intracardiac echocardiography (ICE) ultrasound catheters. The ASIC is implemented in 60 V 0.18-µm HV-BCD technology, integrating Tx beamformers with high voltage pulsers and Rx front end in the same chip, which occupies 2.6 × 11 mm2 that can fit in the catheter size of 9 F (<3 mm). The proposed system reduces the number of wires from >64 to only 22 by integrating Tx beamformer that is programmable using a single low-voltage differential signaling data line. In Rx mode, the system uses 8:1 TDM with direct digital demultiplexing providing raw channel data that enables dynamic Rx beamforming using individual array elements. This system has been successfully used for B-mode imaging on standard ultrasound phantom with 401 mW of average power consumption. The ASIC has a compact element pitch-matched layout, which is also compatible with capacitive micromachined ultrasound transducer on CMOS application. This system addresses cable number and dimensional restrictions in catheters to enable ICE imaging under magnetic resonance imaging by reducing radio frequency induced heating.

HIFU Drive System Miniaturization Using Harmonic Reduced Pulsewidth Modulation.

Switched excitation has the potential to improve on the cost, efficiency, and size of the linear amplifier circuitry currently used in high-intensity focused ultrasound (HIFU) systems. Existing switching schemes are impaired by high harmonic distortion or lack array apodisation capability, so require adjustable supplies and/or large power filters to be useful. A multilevel pulsewidth modulation (PWM) topology could address both of these issues but the switching-speed limitations of transistors mean that there are a limited number of pulses available in each waveform cycle. In this study, harmonic reduction PWM (HRPWM) is proposed as an algorithmic solution to the design of switched waveforms. Its appropriateness for HIFU was assessed by design of a high power five-level unfiltered amplifier and subsequent thermal-only lesioning of ex vivo chicken breast. Three switched waveforms of different electrical powers (16, 26, 35 W) were generated using the HRPWM algorithm. Lesion sizes were measured and compared with those made at the same electrical power using a linear amplifier and bi-level excitation. HRPWM produced symmetric, thermal-only lesions that were the same size as their linear amplifier equivalents ( ). At 16 W, bi-level excitation produced smaller lesions but at higher power levels large transients in the acoustic waveform nucleated undesired cavitation. These results demonstrate that HRPWM can minimize HIFU drive circuity size without the need for filters to remove harmonics or adjustable power supplies to achieve array apodisation.

Combining Acoustic Trapping With Plane Wave Imaging for Localized Microbubble Accumulation in Large Vessels.

The capability of accumulating microbubbles using ultrasound could be beneficial for enhancing targeted drug delivery. When microbubbles are used to deliver a therapeutic payload, there is a need to track them, for a localized release of the payload. In this paper, a method for localizing microbubble accumulation with fast image guidance is presented. A linear array transducer performed trapping of microbubble populations interleaved with plane wave imaging, through the use of a composite pulse sequence. The acoustic trap in the pressure field was created parallel with the direction of flow in a model of a vessel section. The acoustic trapping force resultant from the large gradients in the acoustic field was engendered to directly oppose the flowing microbubbles. This was demonstrated numerically with field simulations, and experimentally using an Ultrasound Array Research Platform II. SonoVue microbubbles at clinically relevant concentrations were pumped through a tissue-mimicking flow phantom and exposed to either the acoustic trap or a control ultrasonic field composed of a single-peak acoustic radiation force beam. Under the flow condition at a shear rate of 433 s-1, the use of the acoustic trap led to lower speed estimations ( ) in the center of the acoustic field, and an enhancement of 71% ± 28%( ) in microbubble image brightness.

Implementation of an evidence-based model of care for low back pain in emergency departments: protocol for the Sydney Health Partners Emergency Department (SHaPED) trial.

INTRODUCTION: Patients with low back pain often seek care in emergency departments, but the problem is that many patients receive unnecessary or ineffective interventions and at the same time miss out on the basics of care, such as advice on self-management. This pattern of care has important consequences for the healthcare system (expensive and inefficient) and for patients (poor health outcomes). We hypothesised that the implementation of an evidence-based model of care for low back pain will improve emergency care by reducing inappropriate overuse of tests and treatments and improving patient outcomes. METHODS AND ANALYSIS: A stepped-wedge cluster randomised controlled trial will be conducted to implement and evaluate the use of the Agency for Clinical Innovation (ACI) model of care for acute low back pain at four emergency departments in New South Wales, Australia. Clinician participants will be emergency physicians, nurses and physiotherapists. Codes from the Systematised Nomenclature of Medicine-Clinical Terms-Australian version will be used to identify low back pain presentations. The intervention, targeting emergency clinicians, will comprise educational materials and seminars and an audit and feedback approach. Health service delivery outcomes are routinely collected measures of imaging (primary outcome), opioid use and inpatient admission. A random subsample of 200 patient participants from each trial period will be included to measure patient outcomes (pain intensity, physical function, quality of life and experience with emergency service). The effectiveness of the intervention will be assessed by comparing the postintervention period with the retrospective baseline control period. ETHICS AND DISSEMINATION: The study received ethical approval from the Sydney Local Health District (Royal Prince Alfred Hospital zone) Ethics Committee (X17-0043). The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: ACTRN 12617001160325.

An Adaptive Array Excitation Scheme for the Unidirectional Enhancement of Guided Waves.

Control over the direction of wave propagation allows an engineer to spatially locate defects. When imaging with longitudinal waves, time delays can be applied to each element of a phased array transducer to steer a beam. Because of the highly dispersive nature of guided waves (GWs), this beamsteering approach is suboptimal. More appropriate time delays can be chosen to direct a GW if the dispersion relation of the material is known. Existing techniques, however, need a priori knowledge of material thickness and acoustic velocity, which change as a function of temperature and strain. The scheme presented here does not require prior knowledge of the dispersion relation or properties of the specimen to direct a GW. Initially, a GW is generated using a single element of an array transducer. The acquired waveforms from the remaining elements are then processed and retransmitted, constructively interfering with the wave as it travels across the spatial influence of the transducer. The scheme intrinsically compensates for the dispersion of the waves, and thus can adapt to changes in material thickness and acoustic velocity. The proposed technique is demonstrated in simulation and experimentally. Dispersion curves from either side of the array are acquired to demonstrate the scheme's ability to direct a GW in an aluminum plate. The results show that unidirectional enhancement is possible without a priori knowledge of the specimen using an arbitrary pitch array transducer. The experimental results show a 34-dB enhancement in one direction compared with the other.

Direct Digital Demultiplexing of Analog TDM Signals for Cable Reduction in Ultrasound Imaging Catheters.

In real-time catheter-based 3-D ultrasound imaging applications, gathering data from the transducer arrays is difficult, as there is a restriction on cable count due to the diameter of the catheter. Although area and power hungry multiplexing circuits integrated at the catheter tip are used in some applications, these are unsuitable for use in small sized catheters for applications, such as intracardiac imaging. Furthermore, the length requirement for catheters and limited power available to on-chip cable drivers leads to limited signal strength at the receiver end. In this paper, an alternative approach using analog time-division multiplexing (TDM) is presented, which addresses the cable restrictions of ultrasound catheters. A novel digital demultiplexing technique is also described, which allows for a reduction in the number of analog signal processing stages required. The TDM and digital demultiplexing schemes are demonstrated for an intracardiac imaging system that would operate in the 4- to 11-MHz range. A TDM integrated circuit (IC) with an 8:1 multiplexer is interfaced with a fast analog-to-digital converter (ADC) through a microcoaxial catheter cable bundle, and processed with a field-programmable gate array register-transfer level simulation. Input signals to the TDM IC are recovered with -40-dB crosstalk between the channels on the same microcoax, showing the feasibility of this system for ultrasound imaging applications.

Superharmonic imaging with chirp coded excitation: filtering spectrally overlapped harmonics.

Superharmonic imaging improves the spatial resolution by using the higher order harmonics generated in tissue. The superharmonic component is formed by combining the third, fourth, and fifth harmonics, which have low energy content and therefore poor SNR. This study uses coded excitation to increase the excitation energy. The SNR improvement is achieved on the receiver side by performing pulse compression with harmonic matched filters. The use of coded signals also introduces new filtering capabilities that are not possible with pulsed excitation. This is especially important when using wideband signals. For narrowband signals, the spectral boundaries of the harmonics are clearly separated and thus easy to filter; however, the available imaging bandwidth is underused. Wideband excitation is preferable for harmonic imaging applications to preserve axial resolution, but it generates spectrally overlapping harmonics that are not possible to filter in time and frequency domains. After pulse compression, this overlap increases the range side lobes, which appear as imaging artifacts and reduce the Bmode image quality. In this study, the isolation of higher order harmonics was achieved in another domain by using the fan chirp transform (FChT). To show the effect of excitation bandwidth in superharmonic imaging, measurements were performed by using linear frequency modulated chirp excitation with varying bandwidths of 10% to 50%. Superharmonic imaging was performed on a wire phantom using a wideband chirp excitation. Results were presented with and without applying the FChT filtering technique by comparing the spatial resolution and side lobe levels. Wideband excitation signals achieved a better resolution as expected, however range side lobes as high as -23 dB were observed for the superharmonic component of chirp excitation with 50% fractional bandwidth. The proposed filtering technique achieved >50 dB range side lobe suppression and improved the image quality without affecting the axial resolution.

The effect of amplitude modulation on subharmonic imaging with chirp excitation.

Subharmonic generation from ultrasound contrast agents depends on the spectral and temporal properties of the excitation signal. The subharmonic response can be improved by using wideband and long-duration signals. However, for sinusoidal tone-burst excitation, the effective bandwidth of the signal is inversely proportional to the signal duration. Linear frequency-modulated (LFM) and nonlinear frequency-modulated (NLFM) chirp excitations allow independent control over the signal bandwidth and duration; therefore, in this study LFM and NLFM signals were used for the insonation of microbubble populations. The amplitude modulation of the excitation waveform was achieved by applying different window functions. A customized window was designed for the NLFM chirp excitation by focusing on reducing the spectral leakage at the subharmonic frequency and increasing the subharmonic generation from microbubbles. Subharmonic scattering from a microbubble population was measured for various excitation signals and window functions. At a peak negative pressure of 600 kPa, the generated subharmonic energy by ultrasound contrast agents was 15.4 dB more for NLFM chirp excitation with 40% fractional bandwidth when compared with tone-burst excitation. For this reason, the NLFM chirp with a customized window was used as an excitation signal to perform subharmonic imaging in an ultrasound flow phantom. Results showed that the NLFM waveform with a customized window improved the subharmonic contrast by 4.35 ± 0.42 dB on average over a Hann-windowed LFM excitation.

Width-modulated square-wave pulses for ultrasound applications.

A method of output pressure control for ultrasound transducers using switched excitation is described. The method generates width-modulated square-wave pulse sequences that are suitable for driving ultrasound transducers using MOSFETs or similar devices. Sequences are encoded using an optimized level-shifted, carrier-comparison, pulse-width modulation (PWM) strategy derived from existing PWM theory, and modified specifically for ultrasound applications. The modifications are: a reduction in carrier frequency so that the smallest number of pulses are generated and minimal switching is necessary; alteration of a linear carrier form to follow a trigonometric relationship in accordance with the expected fundamental output; and application of frequency modulation to the carrier when generating frequency-modulated, amplitude- tapered signals. The PWM method permits control of output pressure for arbitrary waveform sequences at diagnostic frequencies (approximately 5 MHz) when sampled at 100 MHz, and is applicable to pulse shaping and array apodization. Arbitrary waveform generation capability is demonstrated in simulation using convolution with a transducer's impulse response, and experimentally with hydrophone measurement. Benefits in coded imaging are demonstrated when compared with fixed-width square-wave (pseudo-chirp) excitation in coded imaging, including reduction in image artifacts and peak side-lobe levels for two cases, showing 10 and 8 dB reduction in peak side-lobe level experimentally, compared with 11 and 7 dB reduction in simulation. In all cases, the experimental observations correlate strongly with simulated data.

Phase-inversion-based selective harmonic elimination (PI-SHE) in multi-level switched-mode tone- and frequency-modulated excitation.

Switched-mode operation allows the miniaturization of excitation circuitry but suffers from high harmonic distortion. This paper presents a method of phase-inversion-based selective harmonic elimination (PI-SHE) and the use of multiple switching levels. PI-SHE is shown to enable multiples of any selected harmonic to be eliminated through controlled timing of the transition between different excitation voltage levels. Multiples of the third harmonic are shown to be eliminated in three-level tone waveforms. In addition, multiples of the fifth harmonic are shown to be eliminated using five-level tone waveforms. A method of calculating the expected amplitude of each harmonic is presented. The application of PI-SHE in linear frequency-modulated (LFM) excitation is proposed. A heuristic derivation of the spectral properties of multilevel switched LFM waveforms is presented. The performance of the proposed PI-SHE method is confirmed through experimental measurement of the harmonics present in an ultrasound wave using two, three, and five levels for both tone and LFM excitation. The proposed method of controlling harmonics through the use of multilevel switched excitation is especially suitable for applications in which portability, high channel counts, and precise harmonic control are required.

Ultrasound array transmitter architecture with high timing resolution using embedded phase-locked loops.

Coarse time quantization of delay profiles within ultrasound array systems can produce undesirable side lobes in the radiated beam profile. The severity of these side lobes is dependent upon the magnitude of phase quantization error--the deviation from ideal delay profiles to the achievable quantized case. This paper describes a method to improve interchannel delay accuracy without increasing system clock frequency by utilizing embedded phase-locked loop (PLL) components within commercial field-programmable gate arrays (FPGAs). Precise delays are achieved by shifting the relative phases of embedded PLL output clocks in 208-ps steps. The described architecture can achieve the necessary interelement timing resolution required for driving ultrasound arrays up to 50 MHz. The applicability of the proposed method at higher frequencies is demonstrated by extrapolating experimental results obtained using a 5-MHz array transducer. Results indicate an increase in transmit dynamic range (TDR) when using accurate delay profiles generated by the embedded-PLL method described, as opposed to using delay profiles quantized to the system clock.

Antibiotic prophylaxis at triage for simple traumatic wounds: a pilot study.

Antibiotic administration at the time of wound manipulation has not been shown to decrease infection rates for simple traumatic wounds. Antibiotic administration at the time of initial emergency department (ED) presentation, however, has not been explored. Patients presenting to the ED with simple traumatic wounds received 1 g of oral flucloxacillin, or identical placebo, at triage. Wound closure was completed at the discretion of a physician blinded to study contents. Wound infection rates were determined at 1 month. Time from drug administration to wound manipulation was 64.3 min [95% confidence interval (CI) 36.6-91.9] placebo versus 75.0 min (95% CI: 51.7-98.3) flucloxacillin, P=0.657. Six of 36 patients (17%) reported wound infection in the placebo group, and four of 34 (12%) in the flucloxacillin group, P=0.736. Administration of oral flucloxacillin at triage failed to reduce the rate of wound infection for simple traumatic wounds closed in the ED.

Separation of overlapping linear frequency modulated (LFM) signals using the fractional fourier transform.

Linear frequency modulated (LFM) excitation combined with pulse compression provides an increase in SNR at the receiver. LFM signals are of longer duration than pulsed signals of the same bandwidth; consequently, in many practical situations, maintaining temporal separation between echoes is not possible. Where analysis is performed on individual LFM signals, a separation technique is required. Time windowing is unable to separate signals overlapping in time. Frequency domain filtering is unable to separate signals with overlapping spectra. This paper describes a method to separate time-overlapping LFM signals through the application of the fractional Fourier transform (FrFT), a transform operating in both time and frequency domains. A short introduction to the FrFT and its operation and calculation are presented. The proposed signal separation method is illustrated by application to a simulated ultrasound signal, created by the summation of multiple time-overlapping LFM signals and the component signals recovered with ±0.6% spectral error. The results of an experimental investigation are presented in which the proposed separation method is applied to time-overlapping LFM signals created by the transmission of a LFM signal through a stainless steel plate and water-filled pipe.

Amperometric, screen-printed, glucose biosensor for analysis of human plasma samples using a biocomposite water-based carbon ink incorporating glucose oxidase.

This paper describes the optimisation of a screen-printing water-based carbon ink containing cobalt phthalocyanine (CoPC) and glucose oxidase (GOD) for the fabrication of a glucose biosensor. To optimise the performance of the biosensor, the loadings of the electrocatalyst (CoPC) and enzyme (GOD) were varied. It was found that the maximum linear range was achieved with a CoPC loading of 20% (m/m, relative to the mass of carbon) and a GOD loading of 628 U per gram of carbon. In our studies we chose to employ chronoamperometry, as this technique is commonly used for commercial devices. The optimum operating applied potential was found to be +0.5 V, following an incubation period of 60 s. The optimum supporting electrolyte was found to be 0.05 M phosphate buffer at pH 8.0, which resulted in a linear range of 0.2-5 mM, the former represents the detection limit. The sensitivity was 1.12 microA mM(-1). The effect of temperature was also investigated, and it was found that 40 degrees C gave optimal performance. The resulting amperometric biosensors were evaluated by measuring the glucose concentrations for 10 different human plasma samples containing endogenous glucose and also added glucose. The same samples were analysed by a standard spectrophotometric method, and the results obtained by the two different methods were compared. A good correlation coefficient (R(2) = 0.95) and slope (0.98) were calculated from the experimental data, indicating that the new devices hold promise for biomedical studies.

A novel, disposable, screen-printed amperometric biosensor for glucose in serum fabricated using a water-based carbon ink.

Screen-printed amperometric glucose biosensors have been fabricated using a water-based carbon ink. The enzyme glucose oxidase (GOD) and the electro-catalyst cobalt phthalocyanine were mixed with the carbon ink prior to the screen-printing process; therefore, biosensors are prepared in a one-step fabrication procedure. Optimisation of the biosensor performance was achieved by studying the effects of pH, buffer strength, and applied potential on the analytical response. Calibration studies were performed under optimum conditions, using amperometry in stirred solution, with an operating potential of +500 mV versus SCE. The sensitivity was found to be 1170 nA mM(-1), with a linear range of 0.025-2 mM; the former represents the detection limit. The disposable amperometric biosensor was evaluated by carrying out replicate determinations on a sample of bovine serum. This was achieved by the method of multiple standard additions and included a correction for background currents arising from oxidizable serum components. The mean serum concentration was calculated to be 8.63 mM and compared well with the supplier's value of 8.3 mM; the coefficient of variation was calculated to be 3.3% (n=6).