Showing papers in "IEEE Transactions on Biomedical Circuits and Systems in 2008"

A Frequency Control Method for Regulating Wireless Power to Implantable Devices

Abstract: This paper presents a method to regulate the power transferred over a wireless link by adjusting the resonant operating frequency of the primary converter. A significant advantage of this method is that effective power regulation is maintained under variations in load, coupling and circuit parameters. This is particularly important when the wireless supply is used to power implanted medical devices where substantial coupling variations between internal and external systems is expected. The operating frequency is changed dynamically by altering the effective tuning capacitance through soft switched phase control. A thorough analysis of the proposed system has been undertaken, and experimental results verify its functionality.

Energy Efficient Medium Access Protocol for Wireless Medical Body Area Sensor Networks

Abstract: This paper presents a novel energy-efficient MAC Protocol designed specifically for wireless body area sensor networks (WBASN) focused towards pervasive healthcare applications. Wireless body area networks consist of wireless sensor nodes attached to the human body to monitor vital signs such as body temperature, activity or heart-rate. The network adopts a master-slave architecture, where the body-worn slave node periodically sends sensor readings to a central master node. Unlike traditional peer-to-peer wireless sensor networks, the nodes in this biomedical WBASN are not deployed in an ad hoc fashion. Joining a network is centrally managed and all communications are single-hop. To reduce energy consumption, all the sensor nodes are in standby or sleep mode until the centrally assigned time slot. Once a node has joined a network, there is no possibility of collision within a cluster as all communication is initiated by the central node and is addressed uniquely to a slave node. To avoid collisions with nearby transmitters, a clear channel assessment algorithm based on standard listen-before-transmit (LBT) is used. To handle time slot overlaps, the novel concept of a wakeup fallback time is introduced. Using single-hop communication and centrally controlled sleep/wakeup times leads to significant energy reductions for this application compared to more ldquoflexiblerdquo network MAC protocols such as 802.11 or Zigbee. As duty cycle is reduced, the overall power consumption approaches the standby power. The protocol is implemented in hardware as part of the Sensiumtrade system-on-chip WBASN ASIC, in a 0.13- mum CMOS process.

Power-Efficient Impedance-Modulation Wireless Data Links for Biomedical Implants

Abstract: We analyze the performance of wireless data telemetry links for implanted biomedical systems. An experimental realization of a bidirectional half-duplex link that uses near-field inductive coupling between the implanted system and an external transceiver is described. Our system minimizes power consumption in the implanted system by using impedance modulation to transmit high-bandwidth information in the uplink direction, i.e., from the implanted to the external system. We measured a data rate of 2.8 Mbps at a bit error rate (BER) of <10-6 (we could not measure error rates below 10-6 ) and a data rate of 4.0 Mbps at a BER of 10-3. Experimental results also demonstrate data transfer rates up to 300 kbps in the opposite, i.e., downlink direction. We also perform a theoretical analysis of the bit error rate performance. An important effect regarding the asymmetry of rising and falling edges that is inherent to impedance modulation is predicted by theory and confirmed by experiment. The link dissipates 2.5 mW in the external system and only 100 muW in the implanted system, making it among the most power-efficient inductive data links reported. Our link is compatible with FCC regulations on radiated emissions.

A New Antispoofing Approach for Biometric Devices

Abstract: The deployment of fingerprint sensors is increasingly becoming common and has now gained high user acceptance. However, fingerprint sensors are susceptible to spoofing using artificial materials or in worst case to the dismembered fingers. Fake/gummy fingerprints have shown to fool most commercial fingerprint systems. This paper proposes a new method of anti-spoofing using reliable liveness detection. The proposed method of liveness detection is based on the principle of pulse oximetry and involves the source of light originating from a probe at two wavelengths. The light is partly absorbed by haemoglobin, by amounts which differ depending on whether it is saturated with oxygen or deoxygenated haemoglobin. We then perform the computations for the absorption at two wavelengths to estimate the proportion of haemoglobin which is oxygenated. The computed percentage of oxygen in the blood, along with the heart pulse rate, determines the liveness of the enrolled biometric. Our experimental results demonstrate that the developed prototype can successfully thwart the spoof attacks (including those based on dismembered fingers).

An Integrated Implantable Stimulator That is Fail-Safe Without Off-Chip Blocking-Capacitors

Abstract: We present a neural stimulator chip with an output stage (electrode driving circuit) that is fail-safe under single-fault conditions without the need for off-chip blocking-capacitors. To miniaturize the stimulator output stage two novel techniques are introduced. The first technique is a new current generator circuit reducing to a single step the translation of the digital input bits into the stimulus current, thus minimizing silicon area and power consumption compared to previous works. The current generator uses voltage-controlled resistors implemented by MOS transistors in the deep triode region. The second technique is a new stimulator output stage circuit with blocking-capacitor safety protection using a high-frequency current-switching (HFCS) technique. Unlike conventional stimulator output stage circuits for implantable functional electrical stimulation (FES) systems which require blocking-capacitors in the microfarad range, our proposed approach allows capacitance reduction to the picofarad range, thus the blocking-capacitors can be integrated on-chip. The prototype four-channel neural stimulator chip was fabricated in XFAB's 1-mum silicon-on-insulator CMOS technology and can operate from a power supply between 5-18 V. The stimulus current is generated by active charging and passive discharging. We obtained recordings of action potentials and a strength-duration curve from the sciatic nerve of a frog with the stimulator chip which demonstrate the HFCS technique. The average power consumption for a typical 1-mA 20-Hz single-channel stimulation using a book electrode, is 200 muW from a 6 V power supply. The silicon area occupation is 0.38 mm2 per channel.

Low-Power Circuits for Brain–Machine Interfaces

Abstract: This paper presents work on ultra-low-power circuits for brain–machine interfaces with applications for paralysis prosthetics, stroke, Parkinson's disease, epilepsy, prosthetics for the blind, and experimental neuroscience systems. The circuits include a micropower neural amplifier with adaptive power biasing for use in multi-electrode arrays; an analog linear decoding and learning architecture for data compression; low-power radio-frequency (RF) impedance-modulation circuits for data telemetry that minimize power consumption of implanted systems in the body; a wireless link for efficient power transfer; mixed-signal system integration for efficiency, robustness, and programmability; and circuits for wireless stimulation of neurons with power-conserving sleep modes and awake modes. Experimental results from chips that have stimulated and recorded from neurons in the zebra finch brain and results from RF power-link, RF data-link, electrode-recording and electrode-stimulating systems are presented. Simulations of analog learning circuits that have successfully decoded prerecorded neural signals from a monkey brain are also presented.

Stimulus-Artifact Elimination in a Multi-Electrode System

Abstract: To fully exploit the recording capabilities provided by current and future generations of multi-electrode arrays, some means to eliminate the residual charge and subsequent artifacts generated by stimulation protocols is required. Custom electronics can be used to achieve such goals, and by making them scalable, a large number of electrodes can be accessed in an experiment. In this work, we present a system built around a custom 16-channel IC that can stimulate and record, within 3 ms of the stimulus, on the stimulating channel, and within 500 mus on adjacent channels. This effectiveness is achieved by directly discharging the electrode through a novel feedback scheme, and by shaping such feedback to optimize electrode behavior. We characterize the different features of the system that makes such performance possible and present biological data that show the system in operation. To enable this characterization, we present a framework for measuring, classifying, and understanding the multiple sources of stimulus artifacts. This framework facilitates comparisons between artifact elimination methodologies and enables future artifact studies.

An Active 2-D Silicon Cochlea

Abstract: In this paper, we present an analog integrated circuit design for an active 2-D cochlea and measurement results from a fabricated chip. The design includes a quality factor control loop that incorporates some of the nonlinear behavior exhibited in the real cochlea. This control loop varies the gain and the frequency selectivity of each cochlear resonator based on the amplitude of the input signal.

A Partial-Current-Steering Biphasic Stimulation Driver for Vestibular Prostheses

Abstract: This paper describes a novel partial-current-steering stimulation circuit for implantable vestibular prostheses. The drive hardware momentarily delivers a charge-balanced asymmetric stimulus to a dummy load before steering towards the stimulation electrodes. In this fashion, power is conserved while still gaining from the benefits of current steering. The circuit has been designed to be digitally programmable as part of an implantable vestibular prosthesis. The hardware has been implemented in AMS 0.35 mum 2P4M CMOS technology.

An Address-Event Fall Detector for Assisted Living Applications

Abstract: In this paper, we describe an address-event vision system designed to detect accidental falls in elderly home care applications. The system raises an alarm when a fall hazard is detected. We use an asynchronous temporal contrast vision sensor which features sub-millisecond temporal resolution. The sensor reports a fall at ten times higher temporal resolution than a frame-based camera and shows 84% higher bandwidth efficiency as it transmits fall events. A lightweight algorithm computes an instantaneous motion vector and reports fall events. We are able to distinguish fall events from normal human behavior, such as walking, crouching down, and sitting down. Our system is robust to the monitored person's spatial position in a room and presence of pets.

Wearable Monitoring of Seated Spinal Posture

Abstract: This work describes the evaluation of a wearable plastic optical fiber (POF) sensor for monitoring seated spinal posture, as compared to a conventional expert visual analysis, and the development of a field-deployable posture monitoring system. A garment-integrated POF sensor was developed and tested on nine healthy subjects. Data from the wearable sensor were compared to data taken simultaneously from a marker-based motion capture system, for accuracy and reliability. Peak analysis of the resulting data showed a mean time error of 0.53 plusmn 0.8 s, and a mean value error of 0.64 plusmn 3.1 deg, which represents 14.5% of the average range of motion. Expert determination of transitional (good to bad) posture showed a variation of 20.9% of range of motion. These results indicate that the wearable sensor approximates the accuracy of expert visual analysis, and provides sufficient accuracy of measurement to reliably monitor seated spinal posture.

A Silicon Central Pattern Generator Controls Locomotion in Vivo

Abstract: We present a neuromorphic silicon chip that emulates the activity of the biological spinal central pattern generator (CPG) and creates locomotor patterns to support walking. The chip implements ten integrate-and-fire silicon neurons and 190 programmable digital-to-analog converters that act as synapses. This architecture allows for each neuron to make synaptic connections to any of the other neurons as well as to any of eight external input signals and one tonic bias input. The chip's functionality is confirmed by a series of experiments in which it controls the motor output of a paralyzed animal in real-time and enables it to walk along a three-meter platform. The walking is controlled under closed-loop conditions with the aide of sensory feedback that is recorded from the animal's legs and fed into the silicon CPG. Although we and others have previously described biomimetic silicon locomotor control systems for robots, this is the first demonstration of a neuromorphic device that can replace some functions of the central nervous system in vivo.

Active High Power Conversion Efficiency Rectifier With Built-In Dual-Mode Back Telemetry in Standard CMOS Technology

Abstract: In this paper, we present an active rectifier with high power conversion efficiency (PCE) implemented in a 0.5- mum 5 V standard CMOS technology with two modes of built-in back telemetry; short- and open-circuit. As a rectifier, it ensures a PCE > 80%, taking advantage of active synchronous rectification technique in the frequency range of 0.125-1 MHz. The built-in complementary back telemetry feature can be utilized in implantable microelectronic devices (IMD), wireless sensors, and radio frequency identification (RFID) applications to reduce the silicon area, increase the data rate, and improve the reading range and robustness in load shift keying (LSK).

A Low-Power CMOS Front-End for Photoplethysmographic Signal Acquisition With Robust DC Photocurrent Rejection

Abstract: A micro-power CMOS front-end, consisting of a transimpedance amplifier (TIA) and an ultralow cutoff frequency lowpass filter for the acquisition of photoplethysmographic signal (PPG) is presented. Robust DC photocurrent rejection for the pulsed signal source is achieved through a sample-and-hold stage in the feed-forward signal path and an error amplifier in the feedback path. Ultra-low cutoff frequency of the filter is achieved with a proposed technique that incorporates a pair of current-steering transistors that increases the effective filter capacitance. The design was realized in a 0.35-mum CMOS technology. It consumes 600 muW at 2.5 V, rejects DC photocurrent ranged from 100 nA to 53.6 muA, and achieves lower-band and upper-band - 3-dB cutoff frequencies of 0.46 and 2.8 Hz, respectively.

A Mini-Invasive Long-Term Bladder Urine Pressure Measurement ASIC and System

Abstract: A mini-invasive system for long-term bladder urine pressure measurement system is presented. Not only is the design cost reduced, but also the reliability is enhanced by using a 1-atm canceling sensing instrumentation amplifier (IA). Because the urine pressure inside the bladder does not vary drastically, both the sleeping and working modes are required in order to save the battery power for long-term observation. The IA amplifies the signal sensed by the pressure sensor, which is then fed into the following analog-to-digital converter. Owing to the intrinsic 1-atm pressure existing inside the bladder, the IA must be able to cancel such a pressure from the signal picked up by the pressure sensor to keep the required linearity and the resolution for pressure measurement of the bladder urine. The pressure range of the proposed system is found out to be 14.7~19.7 Psi, which covers the range of all of the known unusual bladder syndromes or complications.

A Piezo-Powered Floating-Gate Sensor Array for Long-Term Fatigue Monitoring in Biomechanical Implants

Abstract: Measurement of the cumulative loading statistics experienced by an implant is essential for prediction of long-term fatigue failure. However, the total power that can be harvested using typical in-vivo strain levels is less than 1 muW. In this paper, we present a novel method for long-term, battery-less fatigue monitoring by integrating piezoelectric transduction with hot-electron injection on a floating-gate transistor array. Measured results from a fabricated prototype in a 0.5-mum CMOS process demonstrate that the array can sense, compute, and store loading statistics for over 70000 stress-strain cycles which can be extended to beyond 107 cycles. The measured response also shows excellent agreement with a theoretical model and the nominal power dissipation of the array has been measured to be less than 800 nW.

Robust Engineered Circuit Design Principles for Stochastic Biochemical Networks With Parameter Uncertainties and Disturbances

Abstract: Biochemical regulatory networks including genes, proteins and other regulatory molecules suffer from internal parametrical fluctuations (thermal, transcriptional, and splicing) as well as external noises (environmental and intercellular). Robustness is an essential property of intracellular biochemical regulatory networks to attenuate the effects of internal fluctuation and external noise. In this study, several system control schemes are proposed for the robust circuit control design of stochastic linear and nonlinear biochemical regulatory networks. First, the robust stability of genetic and proteomic regulatory networks is discussed under internal fluctuations. Then, the filtering ability of external noises is analyzed for stochastic biochemical regulatory networks. For the case where a biochemical regulatory network is not sufficiently robust to tolerate internal fluctuation and does not have enough filtering ability to filter the external noise, how to improve the robustness and noise filtering ability of stochastic biochemical regulatory networks by engineered control mechanisms is also proposed via biochemical circuit design. The proposed robust gene circuit design principles have potential applications for robust biosynthetic network design. Finally, two design examples are given in-silico to illustrate the design procedure and to confirm the performance of the proposed robust circuit design method.

A Low-Light CMOS Contact Imager With an Emission Filter for Biosensing Applications

Abstract: In this paper, a fully functional low light 128 X 128 contact image sensor for cell detection in biosensing applications is presented. The imager, fabricated in 0.18 mum CMOS technology, provides low-noise operation by employing both a modified version of the active reset (AR) technique and a modified version of the active column sensor (ACS) readout method. High-sensitivity, low noise performance of the presented sensor is well-suited for fluorescence imaging. For this purpose, an emission filter was fabricated and integrated with the sensor. The filter was fabricated using PDMS and Sudan II Blue dye mix, spin-coated and deposited in a class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450 nm and above. The fabricated imager architecture and operation are described, noise analysis is presented and measurements from a test chip are shown. Experimental results using live neurons from the pond snail, Lymnaea stagnalis, and fluorescence polystyrene micro-beads prove the functionality of the fabricated system and indicate its biocompatiblity.

A Wireless IC for Wide-Range Neurochemical Monitoring Using Amperometry and Fast-Scan Cyclic Voltammetry

Abstract: An integrated circuit for real-time wireless monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting measurements in both fast-scan cyclic voltammetry (FSCV) and amperometry modes for a wide input current range. The chip architecture employs a second-order DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed transmitter operating near 433 MHz. It is fabricated using the AMI 0.5-mum double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. A measured current resolution of 12 pA at a sampling rate of 100 Hz and 132 pA at a sampling rate of 10 kHz is achieved in amperometry and 300-V/s FSCV modes, respectively, for any input current in the range of plusmn430 nA. The modulator core and the transmitter draw 22 and 400 muA from a 2.6-V power supply, respectively. The chip has been externally interfaced with a carbon-fiber microelectrode implanted acutely in the caudate-putamen of an anesthetized rat, and, for the first time, extracellular levels of dopamine elicited by electrical stimulation of the medial forebrain bundle have been successfully recorded wirelessly using 300-V/s FSCV.

A 1.2-V 140-nW 10-bit Sigma–Delta Modulator for Electroencephalogram Applications

Abstract: This paper presents a second-order Sigma-Delta modulator for electroencephalogram applications with 10 bits of resolution, 1.2 V of supply voltage, and only 140 nW of power consumption over a bandwidth of 25 Hz. Low-voltage operation has been achieved using quasi-floating-gate-based circuits. The use of a new class-AB operational amplifier in weak inversion allows very low power consumption. Experimental results show an energy efficiency of 1.6 pJ per quantization level, making it the most energy-efficient converter reported to date in the very low signal bandwidth range.

A Real-Time Multi-Channel Monitoring System for Stem Cell Culture Process

Abstract: A novel, up to 128 channels, multi-parametric physiological measurement system suitable for monitoring hematopoietic stem cell culture processes and cell cultures in general is presented in this paper. The system aims to measure in real-time the most important physical and chemical culture parameters of hematopoietic stem cells, including physicochemical parameters, nutrients, and metabolites, in a long-term culture process. The overarching scope of this research effort is to control and optimize the whole bioprocess by means of the acquisition of real-time quantitative physiological information from the culture. The system is designed in a modular manner. Each hardware module can operate as an independent gain programmable, level shift adjustable, 16 channel data acquisition system specific to a sensor type. Up to eight such data acquisition modules can be combined and connected to the host PC to realize the whole system hardware. The control of data acquisition and the subsequent management of data is performed by the system's software which is coded in LabVIEW. Preliminary experimental results presented here show that the system not only has the ability to interface to various types of sensors allowing the monitoring of different types of culture parameters. Moreover, it can capture dynamic variations of culture parameters by means of real-time multi-channel measurements thus providing additional information on both temporal and spatial profiles of these parameters within a bioreactor. The system is by no means constrained in the hematopoietic stem cell culture field only. It is suitable for cell growth monitoring applications in general.

On the Thermal Elevation of a 60-Electrode Epiretinal Prosthesis for the Blind

Abstract: In this paper, the thermal elevation in the human body due to the operation of a dual-unit epiretinal prosthesis to restore partial vision to the blind affected by irreversible retinal degeneration is presented. An accurate computational model of a 60-electrode device dissipating 97 mW power, currently under clinical trials is developed and positioned in a 0.25 mm resolution, heterogeneous model of the human head to resemble actual conditions of operation of the prosthesis. A novel simple finite difference scheme combining the explicit and the alternating-direction implicit (ADI) method has been developed and validated with existing methods. Simulation speed improvement up to 11 times was obtained for the the head model considered in this work with very good accuracy. Using this method, solutions of the bioheat equation were obtained for different placements of the implant. Comparison with in-vivo experimental measurements showed good agreement.

Defect-Aware High-Level Synthesis and Module Placement for Microfluidic Biochips

Abstract: Recent advances in microfluidics technology have led to the emergence of miniaturized biochip devices, also referred to as lab-on-a-chip, for biochemical analysis. A promising category of microfluidic biochips relies on the principle of electrowetting-on-dielectric, whereby discrete droplets of nanoliter volumes can be manipulated using an array of electrodes. As chemists adapt more bioassays for concurrent execution on such ldquodigitalrdquo droplet-based microfluidic platforms, system integration, design complexity, and the need for defect tolerance are expected to increase rapidly. Automated design tools for defect-tolerant and multifunctional biochips are important for the emerging marketplace, especially for low-cost, portable, and disposable devices for clinical diagnostics. We present a unified synthesis method that combines defect-tolerant architectural synthesis with defect-aware physical design. The proposed approach allows architectural-level design choices and defect-tolerant physical design decisions to be made simultaneously. We use a large-scale protein assay and the polymerase chain reaction procedure as case studies to evaluate the proposed synthesis method. We also carry out simulations based on defect injection to evaluate the robustness of the synthesized biochip designs.

Development of a Time Domain Fluorimeter for Fluorescent Lifetime Multiplexing Analysis

Abstract: We show that a portable, inexpensive USB-powered time domain fluorimeter (TDF) and analysis scheme were developed for use in evaluating a new class of fluorescent lifetime multiplexed dyes. Fluorescent proteins, organic dyes, and quantum dots allow the labeling of more and more individual features within biological systems, but the wide absorption and emission spectra of these fluorophores limit the number of distinct processes which may be simultaneously imaged using spectral separation alone. By additionally separating reporters in a second dimension, fluorescent lifetime multiplexing provides a means to multiply the number of available imaging channels.

An Analog Integrated-Circuit Vocal Tract

Abstract: We present the first experimental integrated-circuit vocal tract by mapping fluid volume velocity to current, fluid pressure to voltage, and linear and nonlinear mechanical impedances to linear and nonlinear electrical impedances. The 275 muW analog vocal tract chip includes a 16-stage cascade of two-port pi-elements that forms a tunable transmission line, electronically variable impedances, and a current source as the glottal source. A nonlinear resistor models laminar and turbulent flow in the vocal tract. The measured SNR at the output of the analog vocal tract is 64, 66, and 63 dB for the first three formant resonances of a vocal tract with uniform cross-sectional area. The analog vocal tract can be used with auditory processors in a feedback speech locked loop-analogous to a phase locked loop-to implement speech recognition that is potentially robust in noise. Our use of a physiological model of the human vocal tract enables the analog vocal tract chip to synthesize speech signals of interest, using articulatory parameters that are intrinsically compact and linearly interpolatable.

Bio-Microfluidics Real-Time Monitoring Using CNN Technology

Abstract: A new non-invasive real-time system for the monitoring and control of microfluidodynamic phenomena involving transport of particles and two phase fluids is proposed. The general purpose design of such system is suitable for in vitro and in vivo experimental setup and, therefore, for microfluidic applications in the biomedical field, such as lab-on-chip and for research studies in the field of microcirculation. The system consists of an ad hoc optical setup for image magnification providing images suitable for acquisition and processing. The main feature of the optical system is the accessibility of the information at any point of the optical path. It was designed and developed using discrete opto-mechanic components mounted on a breadboard. The optical sensing, acquisition, and processing were all performed using an integrated vision system based on cellular nonlinear networks (CNNs) analogic (analog plus logic) technology called focal plane processor (FPP, Eye-RIS, Anafocus) that was inserted in the optical path. Ad hoc algorithms were implemented for the real-time analysis and extraction of fluidodynamic parameters in micro-channels. They were firstly tested on sequences of images recorded during in vivo microcirculation experiments on hamsters and then applied on images acquired and processed in real-time during in vitro experiments on two-phase fluid flow in a continuous microfluidic device (serpentine mixer, ThinXXS).

Effects of Inertia and Wrist Oscillations on Contralateral Neurological Postural Tremor Using the Wristalyzer, a New Myohaptic Device

Abstract: Upper limb postural tremor consists of mechanical-reflex and central-neurogenic oscillations, superimposed upon a background of irregular fluctuations in muscle force. Muscle spindles play key-roles in the information flow to supra-spinal and spinal generators. Oscillations were delivered using a new generation portable myohaptic device, called ldquowristalyzer,rdquo taking into account the ergonomy of upper limbs and allowing a fine adjustment to each configuration of upper limb segments. The nominal torque of the first generation device is 4 Nm, with a maximal rotation velocity of 300 degrees/s and a range of motion of plusmn45 degrees. Reliability was assessed in basal condition and during loading conditions. We assessed the effects of the addition of inertia on postural tremor of the finger in a group of 26 neurological patients and the effects of wrist oscillations upon contralateral postural tremor in 6 control subjects and in 7 neurological patients exhibiting a postural tremor. Patients showed two different behaviors in response to inertia and exhibited an increased variability of postural tremor during fast oscillations (13.3 Hz). One patient with overactivity of the olivocerebellar pathways exhibited a drop in the peak frequency of more than 20%. The relative power of the 8-12 Hz subband was significantly higher in controls both in basal condition and during oscillations (p = 0.028 and p = 0.015, respectively). The second generation wristalyzer allows to investigate the effects of mechanical oscillations up to frequency of 50 Hz. This mechatronic device can assess the responsiveness of tremor generators to stimulation of muscle spindles and biomechanical loading. Potential applications are the monitoring of dysmetria under various inertial or damping conditions, the assessment of rigidity in Parkinson's disease and the characterization of voluntary muscle force.

Micro-Magnetocardiography System With a Single-Chip SQUID Magnetometer Array for QT Analysis and Diagnosis of Myocardial Injury in Small Animals

Abstract: Development of drugs requires electrophysiological studies of small animals like mice, rats or guinea pigs. Electrocardiography (ECG) of hirsute animals is time-consuming. We have developed a micro magnetometer array with a 9-channel superconducting quantum interference device (SQUID) with a 2.5-mm diameter pickup-coil for noncontacting measurement of magnetocardiograms (MCGs) in small animals. The micro-MCG successfully recorded the PQRST complex in mice, rats and guinea pigs. A regional myocardial injury was made in rat hearts with a cryoinjury probe, and the characteristic pattern of the injury was recorded in the MCG. An anterior myocardial injury created a QS pattern in the MCG, and a posterior myocardial injury created a QR pattern in the MCG. Quinidine-induced QT prolongation was successfully detected by micro-MCG in mice and rats. Simultaneous recording of ECG and MCG was conducted after intraperitoneal administration of quinidine (60 mg/kg) in guinea pigs. QT interval corrected for heart rate (QTc) in both ECG and MCG correlated well. The newly developed micro-MCG may facilitate electrophysiological studies of small animals, and may enable high-throughput screening of drug-induced QT abnormality.