A novel, fully implantable, multichannel biotelemetry system for measurement of blood flow, pressure, ECG, and temperature.

Biotelemetry provides high-quality data in awake, free-ranging animals without the effects of anesthesia and surgery. Although many biological parameters can be measured using biotelemetry, simultaneous telemetric measurements of pressure and flow have not been available. The objective of this study was to evaluate simultaneous measurements of blood flow, pressure, ECG, and temperature in a fully implantable system. This novel system allows the measurement of up to four channels of blood flow, up to three channels of pressure, and a single channel each of ECG and temperature. The system includes a bidirectional radio-frequency link that allows the implant to send data and accept commands to perform various tasks. The system is controlled by a base station decoder/controller that decodes the data stream sent by the implant into analog signals. The system also converts the data into a digital data stream that can be sent via ethernet to a remote computer for storage and/or analysis. The system was chronically implanted in swine and alligators for up to 5 wk. Both bench and in vivo animal tests were performed to evaluate system performance. Results show that this biotelemetry system is capable of long-term accurate monitoring of simultaneous blood flow and pressure. The system allows, within the room, recordings, since the implant transmission range is between 6 and 10 m, and, with a relay, backpack transmission distance of up to 500 m can be achieved. This system will have significant utility in chronic models of cardiovascular physiology and pathology.     

Current status of the development of wireless sensors for medical applications]

Wireless near-field transmission has been a challenge for scientists developing medical sensors for a long time. Here, instruments which measure a patient's ECG, oxygen saturation, blood pressure, peak flow, weight, blood glucose etc. are to be equipped with suitable transmission technology. Application scenarios for these sensors can be found in all medical areas where cable connections are irritating for the doctor, patient and other care personnel. This problem is especially common in sport medicine, sleep medicine, emergency medicine and intensive care. Based on its beneficial properties with regard to power consumption, range, data security and network capability, the worldwide standard radio technology Bluetooth was selected to transmit measurements. Since digital data is sent to a receiving station via Bluetooth, the measurement pre-processing now takes place in the patient sensor itself, instead of being processed by the monitor. In this article, a Bluetooth ECG, Bluetooth pulse oximeter, Bluetooth peak flow meter and Bluetooth event recorder will be introduced. On the one hand, systems can be realized with these devices, which allow patients to be monitored online (ECG, pulse oximeter). These devices can also be integrated in disease management programs (peak flow meter) and can be used to monitor high-risk patients in their home environment (event recorder).     

A multichannel telemetry system for autonomic neural signals, blood flow velocity, blood pressure, and ECG measurements]

A radio multichannel telemetry system has been developed for use with chronically instrumented, unrestrained, small animals. The system can simultaneously record autonomic neural signals, blood flow velocity, blood pressure, and ECG. The system is time-multiplexed and pulse width modulation (PWM)/FM device, which employs two sampling frequencies. The system is designed with 10 standard low power integrated circuits, a 3 terminal voltage regulator, and a transistor. The size is 53 x 42 x 20 mm, and the weight, including two batteries is 40 grams. The system is powered by two lithium cells, which provide 60 hours of continuous operation.     

Reevaluation and improved design of the TEM cell in vitro exposure unit for replication studies

The transverse electromagnetic (TEM) cell system developed by Litovitz et al. and utilized by Penafiel et al. for the exposure of cells in T25 flasks at 835 MHz has been reevaluated for the purpose of replicating the studies published by Penafiel. The original setup has been reconstructed as closely as possible, with improvements enabling blinded exposures, forced cooling and better repeatable positioning of the flasks, as well as tight exposure and environmental parameter control. The signal unit can simulate the original signal but also enables various other exposure schemes. The setup has been evaluated for four T25 flasks filled with 5 and 10 ml of cell medium by experimental and numerical means. Comparing E field, SAR and temperature measurements resulted in good agreement: <0.4 dB (4.5%) for E field and 0.48 dB (10.5%) for SAR. The overall average SAR within the medium is 6.0 W/kg at 1 W input power with a standard deviation of less than 52%. The temperature increase was determined to be 0.13 degrees C/(W/kg). This can be reduced to 0.045 degrees C/(W/kg) by applying active air flow cooling. The comparison of SAR values from temperature measurements with the corresponding simulated values resulted in excellent agreement. These results do not correspond to the previous study reporting an average SAR within the medium of 2.5 W/kg at an input power of 0.96 W.     

Measurement of Streaming Potentials of Mammalian Blood Vessels, Aorta and Vena Cava, in Vivo

Attempts to measure streaming potentials in large rabbit blood vessels in vivo have been carried out. Streaming potentials, V(89), were measured by the introduction of microelectrodes through the wall of the blood vessel at separations greater than 1 cm. The outputs from these electrodes fed through calomel cells were amplified and recorded directly by using an Electronics for Medicine photorecorder (White Plains, N. Y.). "Effective streaming currents" were determined by running the output through a low impedence galvanometer while simultaneously measuring the resistance of the circuit V(8) were, therefore, calculated from two measurements and compared. Flow through vessels studied was measured using two different electromagnetic flowmeters. The results indicate that V(8) present in both aorta and vena cava are of the order of 5 to 10 mv. By using the Helmholtz-Smoluchowski equation into which flow was reintegrated, the numbers yield zeta potentials approximating 0.1 to 0.4 v in both aorta and vena cava. This number approaches the apparent upper limit for zeta (actually "interfacial potentials") potentials in biological systems. The measured "i.f." potential is considered as the interreaction of several physical and metabolic factors operating at the blood intimal interface. The polarity of the potential suggests that the interface is negative with respect to the blood flowing through the vessel. Interfacial potential and related V(8) are discussed in terms of their possible importance as a mechanism for maintaining vascular homeostasis in the living animal.     

A patient with dizziness,tachycardia and a DDDR pacemaker

An 84-year-old female patient presented to the coronary care unit with dizziness. A DDD-R minute ventilation sensor pacemaker had been implanted eight years previously. The ECG showed an atrial and ventricular paced rhythm of 140 beats/min. After disconnecting the patient from the cardiac monitor the pacemaker rate dropped gradually to 90 beats/min. The cardiac rhythm monitoring system applies low-amplitude electrical pulses in order to measure respiration rate by transthoracic impedance (TTI) measurement. The minute ventilation pacemaker sensor is driven by the same TTI measurement for rate response. Inappropriate interference between these two systems caused a sensor-driven high pacemaker rate. The dizziness was not related to the sensor-driven high rate.     

The tubular loop fermentor: Oxygen transfer,growth kinetics and design

Oxygen transfer measurements using a dynamic method and evaluated with an appropriate mathematical model have been made on a tubular loop bioreactor. Correlations of the type used in tank systems are used to describe the influence of power and aeration rate on the mass transfer coefficient. Yeast cultures grown on hydrocarbon and glucose substrates show growth characteristics similar to conventional tank results. Model considerations for large-scale tubular fermentors allow for the prediction of the steady-state oxygen profiles and maximum reactor length. Combination with two-phase flow and oxygen transfer correlations yields a design procedure for commercial scale tubular loop fermentors.     

A transient isotopic labeling methodology for 13C metabolic flux analysis of photoautotrophic microorganisms

Metabolic flux analysis is increasingly recognized as an integral component of systems biology. However, techniques for experimental measurement of system-wide metabolic fluxes in purely photoautotrophic systems (growing on CO(2) as the sole carbon source) have not yet been developed due to the unique problems posed by such systems. In this paper, we demonstrate that an approach that balances positional isotopic distributions transiently is the only route to obtaining system-wide metabolic flux maps for purely autotrophic metabolism. The outlined transient (13)C-MFA methodology enables measurement of fluxes at a metabolic steady-state, while following changes in (13)C-labeling patterns of metabolic intermediates as a function of time, in response to a step-change in (13)C-label input. We use mathematical modeling of the transient isotopic labeling patterns of central intermediates to assess various experimental requirements for photoautotrophic MFA. This includes the need for intracellular metabolite concentration measurements and isotopic labeling measurements as a function of time. We also discuss photobioreactor design and operation in order to measure fluxes under precise environmental conditions. The transient MFA technique can be used to measure and compare fluxes under different conditions of light intensity, nitrogen sources or compare strains with various mutations or gene deletions and additions.     

At‐line Determination of Glucose,Ammonia, and Acetate in High Cell Density Cultivations of Escherichia coli

A sophisticated measurement system for at‐line determination of the main C‐source glucose, the by‐product acetate, and the N‐source ammonium for high cell density cultivations (HCDC) of Escherichia coli K12 TG1 is presented. One flow diffusion technique (FDA) system is used for glucose measurement in the range of 0.5 up to 40 gL^–1 in the cultivation broth. Another FDA system detects the amount of the undesired by‐product acetate. The ammonium concentration in the range of 0.2 to 2.5 gL^–1 is determined on‐line by a flow injection analysis (FIA) system. For verification purposes, an HPLC system which is also connected to the bioreactor for at‐line measurements is utilized. Several HCDC with cell densities of more than 100 gL^–1 have been carried out. The courses of growth‐determining substrates have been detected at‐line. All used systems have shown an excellent compliance with off‐line measurements.     

Structure, form, and function of flight in engineering and the living world

By combining appearance and behavior in animals with physical laws, we can get an understanding of the adaptation and evolution of various structures and forms. Comparisons can be made between animal bodies and various technical constructions. Technical science and theory during the latest decades have resulted in considerable insight into biological adaptations, but studies on structures, forms, organs, systems, and processes in the living world, used in the right way, have also aided the engineer in finding wider and better solutions to various problems, among them in the design of micro-air vehicles (MAVs). In this review, I discuss the basis for flight and give some examples of where flight engineering and nature have evolved similar solutions. In most cases technology has produced more advanced structures, but sometimes animals are superior. I include how different animals have solved the problem of producing lift, how animal wings meet the requirements of strength and rigidity, how wing forms are adapted to various flight modes, and how flight kinematics are related to flight behavior and speed. The dynamics of vorticity is summarized. There are a variety of methods for the determination of flight power; it has been estimated adequately by lifting-line theory, by physiological measurements, and from mass loss and food intake. In recent years alternative methods have been used, in which the mechanical power for flight is estimated from flight muscle force used during the downstroke. Refinements of these methods may create new ways of estimating flight power more accurately. MAVs operate at the same Reynolds numbers as large insects and small birds and bats. Therefore, studies on animal flight are valuable for MAV design, which is discussed here.     

A self-heated thermistor technique to measure effective thermal properties from the tissue surface

A microcomputer based instrument to measure effective thermal conductivity and diffusivity at the surface of a tissue has been developed. Self-heated spherical thermistors, partially embedded in an insulator, are used to simultaneously heat tissue and measure the resulting temperature rise. The temperature increase of the thermistor for a given applied power is a function of the combined thermal properties of the insulator, the thermistor, and the tissue. Once the probe is calibrated, the instrument accurately measures the thermal properties of tissue. Conductivity measurements are accurate to 2 percent and diffusivity measurements are accurate to 4 percent. A simplified bioheat equation is used which assumes the effective tissue thermal conductivity is a linear function of perfusion. Since tissue blood flow strongly affects heat transfer, the surface thermistor probe is quite sensitive to perfusion.     

Measuring fetal and maternal temperature differentials: a probe for clinical use during labour

The healthy fetus maintains a higher temperature than that of its mother during gestation and labour. This results from the thermal balance between the heat generated by the fetus and the heat loss to its maternal surroundings. The heat loss can be by heat exchange via blood flowing in the umbilical cord and placenta, and via conduction through the fetal skin and amniotic fluid to the maternal wall. The temperature difference between the fetal and maternal tissue may reflect the metabolic state of the fetus and the magnitude and changing patterns of placental blood flow during labour. Physiological changes, such as those induced by epidural analgesia, and fetal infection have been shown to exhibit an increase in the absolute temperature. An intrauterine probe, previously used for non-invasive ECG detection, has been equipped with temperature sensors that measure fetal and maternal skin temperature in utero. Laboratory tests to characterize the performance of the probe reveal that absolute and differential temperatures can be resolved to around 0.01° C with a thermal time constant of approximately 9 s. Ideally the probe body should have infinite thermal insulation or thermal shunting across the probe will occur reducing the measured temperature difference. In this initial probe design, a high thermal isolation between sensors has been achieved but is not perfect, resulting in around 85% of the actual temperature difference across the probe being registered. Average feto-maternal differences of 0.2° C have been measured in a clinical investigation.     

Quantitative measurements of mixing intensity in shake-flasks and stirred tank reactors. Use of the Mixmeter, a mixing process analyzer

A new mixing probe has been developed which measures the motions of the fluid during mixing as pressure fluctuations and converts the measurements into a mixing signal (MS). The MS is the root mean square (RMS) pressure fluctuation in the 1-64Hz range as determined by a sensitive pressure sensor and a digital signal processor specifically designed for the purpose. The MS is a measure of the actual mixing flow of the fluid rather than a measurement of the input motions or energies into the reactor system (e.g. RPM, torque or power). In other studies, the MS has been measured as a function of mixing speed in numerous sized reactors from 10 to 1000l, and provides consistent and reproducible measurements. The MS increases monotonically as a function of mixing speed, with a change of slope corresponding to the transition from laminar to turbulent mixing regimes. Maps of MS as a function of location in the reactor are useful in understanding stirred tank reactor design and performance. Quantitative measurements of mixing are especially useful during process development as a tool to increase the success of scale-up during the transition from process development to manufacturing. Measurements at a fixed location in a given reactor are useful in understanding changes in mixing that occur during the course of a given process, and are useful in manufacturing situations where validated documentation of lot-to-lot consistency of mixing is required (e.g. pharmaceutical manufacturing). In addition, the probe has been used to measure mixing in vessels with vibrational mixers with similar results. The probe has been successfully used in feedback loops to control either mixing speed or vibrational mixing amplitude in order to maintain constant mixing of the fluid during processing. With this system it is possible to maintain constant mixing over a wide range of fluid volumes in a given reactor, and, for instance, to compensate for changes in viscosity throughout the course of the process. Adaptations of this system for the measurement of mixing in shake-flasks is described in this paper.     

Electromagnetic information transfer through aqueous system

Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.     

Heat balance sap flow gauge for small diameter stems

Applying heat balance sap flow gauges to plant stems <10 mm in diameter has been difficult because a miniature design is needed that can be attached to a range of stem geometries. This report presents a modified gauge design for use on small plant stems of irregular geometry and shows results from Glycine max with stem diameters of 3–4 mm. The gauge was evaluated on container-grown plants by comparing gauge measurements of flow to gravimetric estimates of transpiration. Experiments were conducted in the laboratory and greenhouse, using artificial and natural lighting, respectively. Laboratory comparisons of gauge versus gravimetric water loss measurements indicated that the instrument was accurate to within ±5% when soil water was not limiting. Similar results were obtained from greenhouse tests except when soil water availability was low and cumulative gauge estimates became 30–45% less than gravimetric measurements. Differences may have reflected reduced plant water uptake or errors in sap flow estimates associated with low flow rates. Gauge accuracy was not improved by including the rate change in heat storage (S) in the flow calculations because S was always less then 3% of the total heat balance. Relationships between system temperature and sap flow rate suggested a diagnostic test for determining optimum power input. A time constant of 15 s indicated potential application in many agronomic and physiological studies.     

A fiber optic sensor system for control of rate-adaptive cardiac pacemakers and implantable defibrillators.

Commercially available cardiac pacemakers and implantable cardioverters/defibrillators (ICDs) predominantly use an intracardiac-derived electrocardiogram (ECG) for the detection of arrhythmias. To achieve automatic control of the heart frequency in accordance with cardiovascular strain and improved detection of life-threatening arrhythmias, it is desirable to monitor the heart by an input signal correlated with the hemodynamic state. One possible approach to derive such a signal is to measure the inotropy (mechanical contraction strength of the heart muscle). For this purpose, an optoelectronic measurement system has been designed. The fundamental function of the system has been shown in earlier investigations using an isolated beating pig heart. In this paper the design of two algorithms for use in pacemakers and ICDs based on a fiber optic sensor signal is presented.     

Energy requirements for nitrification and biological nitrogen removal in engineered wetlands

Nitrogen in wastewater degrades aquifer and surface water quality. To protect water quality in the United States, nitrogen discharge standards are strict: typically 1.0 mg/L NH₄-N for discharge to surface water and 10 mg/L total nitrogen (TN) for discharge to soil. Passive constructed wetland treatment systems cannot meet the nitrification standards discussed in this paper, using loading rates commonly considered to be cost-effective based on economic conditions in North America. Although partial nitrification can be achieved with some vertically or intermittently loaded, subsurface flow (SSF) wetlands, complete nitrification cannot be achieved in these passive wetland treatment systems. Engineered wetlands (EWs) use mechanical power inputs via pumping of air or water to nitrify wastewater, and have evolved in large part to nitrify wastewater. The design energy requirements for these power inputs have yet to be described in the wetland treatment literature. Our paper investigates the energy and area requirements of three wetland technologies: aerated subsurface flow, tidal flow, and pulse-fed wetland treatment, compared to a mechanical activated-sludge treatment system.     

An approach to remote monitoring of heart rate variability (HRV) using microwave radar during a calculation task

Recently, nonrestrictive and noninvasive sensing techniques to measure vital signs have been actively researched and developed. This study aimed to develop a prototype system to monitor cardiac activity using microwave radar without making contact with the body and without removing clothing--namely, a completely noncontact, remote monitoring system. In addition, heart rate and changes in heart rate variability (HRV) during simple mental arithmetic tasks were observed with the prototype system. The prototype system has a microwave Doppler radar antenna with 24 GHz frequency and approximately 7 mW output power. The experiments were conducted with seven subjects (23.00±0.82 years). We found that the prototype system captured heart rate and HRV precisely. The strong relationship between the heart rates during tasks (r=0.96), LF (cross-correlation=0.76), and LF/HF (cross-correlation=0.73) of HRV calculated from the prototype system and from electrocardiograph (ECG) measurements were confirmed. The proposed completely noncontact, remote method appears promising for future monitoring of cardiac activity as an indicator of changes in mental workload in workplaces.     

Screening protein refolding using surface plasmon resonance

Surface plasmon resonance (SPR) measurements were used to screen refolding conditions to identify a physicochemical environment which gives an acceptable refolding yield for samples of glutathione-S-transferase (GST) denatured in 6 M guanidine hydrochloride and 32 mM dithiothreitol. The SPR measurements were performed on carboxymethylcellulose coated chips that could accommodate two separate flow paths. One side of the chip was derivatized with immobilized glutathione and the other with goat anti-GST antibody. This created a dual-derivatized chip capable of showing both the presence of GST and providing a measure of enzyme activity. The dual-derivatized chip could be regenerated using a two-step washing procedure and reused to analyze multiple samples from a screening study of protein refolding conditions. SPR measurements have been shown to be suitable for screening protein refolding conditions due to the high sensitivity, ease of chip regeneration and the ability to incorporate a control in the experimental design. The combination of such advantages with the high-throughput automated SPR systems currently available may be a valuable approach to determine conditions suitable for protein refolding following insoluble expression in a bacterial host.     

Dielectric measurements for the design of an electromagnetic rewarming system

The work described in this paper is intended to provide a basis for the design of a controlled rewarming system for cryopreserved tissues and organs using electromagnetic energy. For rapid rewarming (say, greater than 10 degrees C/min), the temperature distribution in the organ is effectively determined by the uniformity (or otherwise) of the power deposition, which is in turn controlled by the electrical properties of the perfused tissue. In this contribution, we describe the measurement system we have used to characterize the electrical properties of perfusates and perfused rabbit kidney tissue from -30 to +20 degrees C. Measurements have been made on three perfusates using an open-ended coaxial probe sensor over a continuous range of radio and microwave frequencies covering 50 MHz to 2.6 GHz. Results show that the behavior of the electrical properties with increasing temperature is unfavorable at either end of the frequency range investigated--either the power absorption has a positive temperature coefficient or the penetration depth is too shallow. However, there is a compromise frequency range, determined in part by the perfusate composition, where these factors are much less serious. In this frequency range, the electrical properties of the perfused tissue are dominated by the properties of the perfusate. Modifications to the perfusate composition, e.g., reducing the concentration of electrolytes by adding sucrose, can further improve the temperature dependence of the electrical properties.