An electrically isolated balanced wideband current source: basic considerations and design

At relatively high frequencies, the application of an alternating current through the body or a body segment results in electromagnetic stray fields which reduce the amount of current actually injected into the tissue under study. This radiation effect can be reduced by use of a symmetrical configuration current source. The symmetry of such an arrangement, however, depends on the stray capacitances of the source with respect to surrouding equipment. To minimise these effects, it is required that the source is electrically isolated from the surrounding equipment and the subject under study. In this manner stray capacitances with respect to elements of the current source are reduced. In such a configuration common mode voltages to the input amplifier of the measuring system are also reduced. The paper describes design considerations and the implementation of a wideband current source capable of injecting alternating current in the order of 300μA_RMS into biological tissue having impedances up to 1kΩ. Current stabilisation is obtained by means of a control circuit which measures the actual current passing through the tissue under study. Leakage currents arising from shielding and stray capacitances are compensated for. The usable frequency range is between 4 kHz and 1024 kHz and current stability is better than 0.2%. Through the use of a symmetrical, floating circuit a configuration is obtained which substantially reduces stray effects. The current source is connected to other circuits by means of two isolation ports: (1) a transformer coupling for the carrier frequency; and (2) an opto-coupler to transfer a phase reference signal obtained from current measurement. The current amplitude can be modulated by controlling the reference input to the control loop by means of a third auxiliary isolation port for transfer of the modulating signal.     

A method for electrical measurements on isolated protoplasmic droplets from Nitella

Summary A special recording chamber has been constructed which allows for the perfusion of the fragile protoplasmic droplets from Nitella cells while making electrical measurements on the preparation.Measurements were made of the potential of the interior of the droplet relative to the bathing medium, under resting conditions and during electrical stimulation. In a bathing medium whose cationic concentration resembled the natural vacuolar sap, a small resting potential of between 0 and –30 mV was observed. Stimulation with depolarizing current shocks of 100 s in duration and of up to 0.28 mA/cm² elicited active responses of up to 130 mV which outlasted the stimulus artifacts. The responses were graded but they resembled nerve action potentials in shape and duration.     

低噪声、低纹波头皮脑电信号采集的前端电路

基于SMIC 0.18 μm CMOS工艺设计了一种由前置放大器、纹波抑制电路、增益可编程放大器和外置低通滤波器组成的低噪声头皮脑电信号采集前端电路。其中前置放大器采用斩波技术来降低低频噪声和失调电压,其结构为电容耦合的斩波稳定放大器,其有源放大部分由折叠式共源共栅级和共源级构成的两级全差分放大器构成,以获得较高的开环增益;同时在前置放大器后引入了阻容耦合电路来抑制在斩波频率处产生的纹波。可编程增益放大器采用可调电容阵列构成的电容负反馈放大器以实现增益逐级可调。Spectre后仿真结果表明,前置放大器的增益为40 dB,共模抑制比可达131 dB,电源抑制比90 dB,输入等效噪声772 nV/sqrt(Hz)@100 Hz;可编程增益放大器的增益分别为12、20、25 dB;低通滤波器的截止频率为1 kHz;纹波抑制电路对在斩波频率处的纹波具有400倍的抑制效果。该前端电路的总增益为40~65 dB,通频带为1 Hz~1 kHz。     

A modified system for in vitro perfusion of isolated renal tubules

A modified system for the in vitro perfusion of isolated tubule segments is presented. The system consists of four holders each of which carries an acrylic cylinder. The acrylic cylinders are used to fix the glass pipettes in a concentric position. The four holders are mounted onto a support consisting of two holding pieces and three steel rods. Three of the holders contain ball-races so that they can slide on the rods with high accuracy and little friction. The holers to which the sylgard pipette and the perfusion pipette are attached are moved by electric motors. Compared with the classical V-track system this modification has the advantage of higher precision. Once the different pipettes are centered, concentricity is maintained even when the pipettes are moved forward or backward. Thus, this equipment facilitates the cannulation of tubules and increases the number of successfull experiments.This study was supported by Deutsche Forschungsgemeinschaft     

Noise characteristic design of CMOS source follower and voltage amplifier for active semiconductor microelectrodes for neural signal recording

A noise performance design method for the pre-amplifiers of an active neural probe is given. The on-chip circuitry of the active neural probe consists of CMOS devices that show high-/ low-frequency noise, so that the device noise can become dominant. Analysis of the signal-to-device-noise ratio (SDNR) for the CMOS source follower buffer and two-stage differential voltage amplifier is given. Closed-form expressions for the output noise power are derived and exploited to tailor the parameters that are controllable during circuit design. The output SDNR is calculated considering the real extracellular action potentials, the electrode-electrolyte interface and the noise spectrum of CMOS devices from typical foundries. It is shown that the output device noise power can be much higher than the output signal power if the devices at the input stage of the pre-amplifier are made as small as given fabrication technology permits. Quantitative information of the circuit parameters to achieve an SDNR higher than 5 for neural spikes with 60μV amplitude are provided for both preamplifier types.     

Computer interface for electrophysiological applications: Simple modifications to a commercial (Datel) single-board data-aquisition system

Commercial single-board data-aquisition systems such as the Datel ST series, often lack a programmable sampling clock and multichannel sample and holds. These features are often vital to biophysical experiments where it is necessary to sample at precise intervals and/or change the sampling rate during an experiment. Additionally, when more than one signal is being sampled during the experiment, the delay between sampling of successive inputs may cause unacceptable phase errors. These phase errors, which are particularly serious for impedance measurements, may be eliminated by sampling both current and voltage simultaneously using two sample-and-hold devices. The way in which the programmable timer and multiple sample-and-holds may be implemented on a commercial interface board is demonstrated. Although the circuits described are specifically intended for the Datel ST-Nova interface, they may be readily adapted to function with the Datel ST series boards for other computers (such as the PDR-11 and LSI-11) as well as for many other commercially available systems.     

A wideband high common mode rejection ratio amplifier and phase-locked loop demodulator for multifrequency impedance measurement

Design considerations and implementation of a multifrequency measuring channel for application in the field of bio-impedance measurement are discussed in this paper. The input amplifier has a differential configuration which is electrically isolated from the remaining circuits. Transformer coupling provides improved common mode rejection when compared to non-isolated input stages. The frequency characteristic of the section between input and demodulator is flat within ±0.1 dB between 4kHz and 1024 kHz. The synchronous demodulator is based on a wideband switched video amplifier. In contrast to commonly used lock-in techniques, the carrier for demodulation is recovered from the input signal by means of a phase-locked loop. This method ensures zero phase shift with respect to the input signal and improves the accuracy of measurement. The system has been developed primarily for thoracic impedance cardiography (TIC) but has also succesfully been applied in the field of total body bio-impedance analysis (BIA). At present an electrical impedance tomograph is under development based on the instrumentation described. Results regarding the measurement range and accuracy are given and some recordings of patient data are shown.     

A system for automated noise parameter measurements on MR preamplifiers and application to high B0 fields

A noise figure and noise parameter measurement system was developed that consists of a combination spectrum and network analyzer, preamplifier, programmable power supply, noise source, tuning board, and desktop computer. The system uses the Y‐factor method for noise figure calculation and allows calibrations to correct for a decrease in excess noise ratio between the noise source and device under test, second stage (system) noise, ambient temperature variations, and available gain of the device under test. Noise parameters are extracted by performing noise figure measurements at several source impedance values obtained by adjusting an electronically controlled tuner. Results for several amplifiers at 128 MHz and 200 MHz agree with independent measurements and with the corresponding datasheets. With some modifications, the system was also used to characterize the noise figure of MRI preamplifiers in strong static magnetic fields up to 9.4 T. In most amplifiers tested the gain was found to be reduced by the magnetic field, while the noise figure increased. These changes are detrimental to signal quality (SNR) and are dependent on the electron mobility and design of the amplifier's semiconductor devices. Consequently, gallium arsenide (GaAs) field‐effect transistors are most sensitive to magnetic fields due to their high electron mobility and long, narrow channel, while silicon–germanium (SiGe) bipolar transistor amplifiers are largely immune due to their very thin base. Copyright © 2014 John Wiley & Sons, Ltd.     

CHI: A contemporaneous health index for degenerative disease monitoring using longitudinal measurements

In this paper, we develop a novel formulation for contemporaneous patient risk monitoring by exploiting the emerging data-rich environment in many healthcare applications, where an abundance of longitudinal data that reflect the degeneration of the health condition can be continuously collected. Our objective, and the developed formulation, is fundamentally different from many existing risk score models for different healthcare applications, which mostly focus on predicting the likelihood of a certain outcome at a pre-specified time. Rather, our formulation translates multivariate longitudinal measurements into a contemporaneous health index (CHI) that captures patient condition changes over the course of progression. Another significant feature of our formulation is that, CHI can be estimated with or without label information, different from other risk score models strictly based on supervised learning. To develop this formulation, we focus on the degenerative disease conditions, for which we could utilize the monotonic progression characteristic (either towards disease or recovery) to learn CHI. Such a domain knowledge leads us to a novel learning formulation, and on top of that, we further generalize this formulation with a capacity to incorporate label information if available. We further develop algorithms to mitigate the challenges associated with the nonsmooth convex optimization problem by first identifying its dual reformulation as a constrained smooth optimization problem, and then, using the block coordinate descent algorithm to iteratively solve the optimization with a derived efficient projection at each iteration. Extensive numerical studies are performed on both synthetic datasets and real-world applications on Alzheimer’s disease and Surgical Site Infection, which demonstrate the utility and efficacy of the proposed method on degenerative conditions that include a wide range of applications.     

A virtual reality simulator for orthopedic basic skills: A design and validation study

Orthopedic drilling as a skill demands high levels of dexterity and expertise from the surgeon. It is a basic skill that is required in many orthopedic procedures. Inefficient drilling can be a source of avoidable medical errors that may lead to adverse events. It is hence important to train and evaluate residents in safe environments for this skill. This paper presents a virtual orthopedic drilling simulator that was designed to provide visiohaptic interaction with virtual bones. The simulation provides a realistic basic training environment for orthopedic surgeons. It contains modules to track and analyze movements of surgeons, in order to determine their surgical proficiency. The simulator was tested with senior surgeons, residents and medical students for validation purposes. Through the multi-tiered testing strategy it was shown that the simulator was able to produce a learning effect that transfers to real-world drilling. Further, objective measures of surgical performance were found to be able to differentiate between experts and novices.     

A new approach to mechanical simulation of lung behaviour: Pressure-controlled and time-related piston movement

A mechanical lung simulator is described (an extension of a previous mechanical simulator) which simulates normal breathing and artificial ventilation in patients. The extended integration of hardware and software offers many new possibilities and advantages over the former simulator. The properties of components which simulate elastance and airway resistance of the lung are defined in software rather than by the mechanical properties of the components alone. Therefore, a more flexible simulation of non-linear behaviour and the cross-over effects of lung properties is obtained. Furthermore, the range of lung compliance is extended to simulate patients with emphysema. The dependency of airway resistance on lung recoil pressure and transmural pressure of the airways can also be simulated. The new approach enables one to incorporate time-related mechanics such as the influence of lung viscosity or cardiac oscillation. The different relations defined in the software can be changed from breath to breath. Three simulations are presented: (1) computer-controlled expiration in the artificially ventilated lung; (2) simulation of normal breathing; and (3) simulation of viscoelastance and cardiac influences during artificial ventilation. The mechanical simulator provides a reproducible and flexible environment for testing new software and equipment in the lung function laboratory and in intensive care, and can be used for instruction and training.     

A laser diffraction system with improved sensitivity for long-time measurements of sarcomere dynamics in isolated cardiac myocytes

To measure the mechanical activity of enzymatically isolated mammalian myocytes the principle of laser light diffraction was used. Since the viability of isolated cardiac myocytes showed a marked dependence on the laser power used, an opto-electronic system with improved light sensitivity and low susceptibility to optical noise was developed. The high sensitivity was achieved by a novel approach in the detection of diffraction patterns, that provides a significant reduction of the amount of laser power required. This improvement rendered possible the application of laser diffraction during extended experiments including pharmacological interventions. The static performance of the system, as assessed by means of calibration gratings, showed a resolution in the order of 5 nm for small changes in sarcomere length in the range from 1.2 m to 2.0 m. Examples of measurements on resting and contracting cells are presented, and the limitations of the application of the system to biological specimens are discussed.     

A comparison of two different indicators: quin 2 and aequorin in isolated single cells and intact strips of ferret portal vein

A comparison between the fluorescent indicator quin 2 and the bioluminescent indicator aequorin was performed in the same smooth muscle cell type. Aequorin was loaded into intact strips and quin was loaded into enzymatically isolated single cells from ferret portal vein. Both indicators gave qualitatively the same calcium profiles when the tissue was challenged with agonists. Quin loading caused a dramatic shift to the right in dose response curves to potassium and phenylephrine. The ED₅₀ values for quin loaded cells were significantly different from those for control cells for both agonists. Intracellular calcium levels at rest were not significantly different with quin and aequorin. Cells stimulated with potassium gave significantly different intracellular calcium values with the two indicators suggesting a change in the stimulated steady state level due to the introduction of an additional calcium buffer (quin2) into the cell.     

A low noise remotely controllable wireless telemetry system for single-unit recording in rats navigating in a vertical maze

The use of cables for recording neural activity limits the scope of behavioral tests used in conscious free-moving animals. Particularly, cable attachments make it impossible to record in three-dimensional (3D) mazes where levels are vertically stacked or in enclosed spaces. Such environments are of particular interest in investigations of hippocampal place cells, in which neural activity is correlated with spatial position in the environment. We developed a flexible miniaturized Bluetooth-based wireless data acquisition system. The wireless module included an 8-channel analogue front end, digital controller, and Bluetooth transceiver mounted on a backpack. Our bidirectional wireless design allowed all data channels to be previewed at 1 kHz sample rate, and one channel, selected by remote control, to be sampled at 10 kHz. Extracellular recordings of neuronal activity are highly susceptible to ambient electrical noise due to the high electrode impedance. Through careful design of appropriate shielding and hardware configuration to avoid ground loops, mains power and Bluetooth hopping frequency noise were reduced sufficiently to yield signal quality comparable to those recorded by wired systems. With this system we were able to obtain single-unit recordings of hippocampal place cells in rats running an enclosed vertical maze, over a range of 5 m.     

A quasi-totally shielded,low-capacitance glass-microelectrode with suitable amplifiers for high-frequency intracellular potential and impedance measurements

The fabrication of a new glass microelectrode for high-speed recording is reported. It consists of a Ling-Gerard microelectrode which is slit into a spacer capillary with the tip slightly protruding. Except for the ultimate tip (of 30 m length) the entire assembly is coated with silver and insulated. After proper insertion into the cell the electrode provides a shield, which extends from the surface of the cell membrane up to the input of the amplifier. This electrode has two advantages: 1. it eliminates all capacitive pickup of bath potentials which is of paramount importance in impedance measurements and 2. if used in conjunction with negative capacitance amplifiers, it allows more faithful high-frequency recordings, than was possible with the conventional techniques, because the capacitance neutralization can be properly set even though the non-ideal transmission properties of the electrode tips are not known. Test experiments using a rapid amplifier circuit of own design show that the electrode assembly allows error-free phaseshift measurements of up to 30 kHz to be obtained with electrodes of 20 M or risetimes (10–90%) of squarewave pulses of 10 to 12 s. The corresponding time constants of 5 to 6 s indicate that the time resolution of the new technique is superior to the apparent time resolution of the conventional techniques.     

Amplifiers for bioelectric events: A design with a minimal number of parts

A design for an amplifier for bioelectric events is presented that has fewer parts than conventional designs. The design allows the construction of amplifiers of a high quality in terms of noise and common mode rejection, with reduced dimensions and with a lower power consumption. Gain, bandwidth and number of channels are easily adapted to a wide range of biomedical applications. An application example is given in the form of a multichannel EEG amplifier (gain is 20000), in which each channel consists of three operational amplifiers (one single and one dual), six resistors and two capacitors. The equivalent input noise voltage and current are 0.15 μV_rms and 1 pA_rms, respectively, in a bandwidth of 0.2–40 Hz, and a common mode rejection ratio of 136 dB is achieved without trimming.     

A high-resolution interval timer and buffered storage system for neurophysiological experiments

A high-resolution interval timer, designed as a computer peripheral for use in neurophysiological experiments, is described. With only minimal intervention by the controlling computer, this device detects, identifies and times the occurrence of discriminated neuronal discharges and changes in experimental status, and autonomously stores these encoded times in an on-board 4K×16 r.a.m. This device reduces the need for detailed software timing routines, while still permitting user selectible resolution (>1 to <100 μs/bit) and asynchronous access to the stored data by the controlling computer. The flexibility of this device and its ability to collect data autonomously make it extremely useful in a wide variety of sensory and behavioural neurophysiological experiments.