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This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

Cardiorespiratory events (CREs), including bradycardia and apnea, in infants are a major concern for physicians and families. Our hypothesis was that there is a difference in the heart rate variability (HRV) of infants who have CREs when compared to normal control infants. The purpose of this study was to develop CRE prediction models based on HRV measured during a polysomnographic (PSG) recording. ANCOVA analysis accounting for factors such as age and sleep state show a relationship between HRV variables and CRE. Prediction models, including neural networks and support vector machines, were developed to predict CRE within either (a) 1-week or (b) 1-month after the PSG. The support vector machine prediction accuracy, for CRE susceptibility one month after the PSG on an independent testing dataset, was 50.0% sensitivity and 82.6% specificity. Although the developed prediction models were not sufficiently accurate for clinical decision making, these results support the potential role of abnormalities in autonomic control of heart rate among infants at risk for CREs.

Studies of food intake and ingestive behavior in free-living conditions most often rely on self-reporting-based methods that can be highly inaccurate. Methods of Monitoring of Ingestive Behavior (MIB) rely on objective measures derived from chewing and swallowing sequences and thus can be used for unbiased study of food intake with free-living conditions. Our previous study demonstrated accurate detection of food intake in simple models relying on observation of both chewing and swallowing. This article investigates methods that achieve comparable accuracy of food intake detection using only the time series of swallows and thus eliminating the need for the chewing sensor. The classification is performed for each individual swallow rather than for previously used time slices and thus will lead to higher accuracy in mass prediction models relying on counts of swallows. Performance of a group model based on a supervised method (SVM) is compared to performance of individual models based on an unsupervised method (K-means) with results indicating better performance of the unsupervised, self-adapting method. Overall, the results demonstrate that highly accurate detection of intake of foods with substantially different physical properties is possible by an unsupervised system that relies on the information provided by the swallowing alone.

Current, validated methods for dietary assessment rely on self-report, which tends to be inaccurate, time-consuming, and burdensome. The objective of this work was to demonstrate the suitability of estimating energy intake using individually-calibrated models based on Counts of Chews and Swallows (CCS models). In a laboratory setting, subjects consumed three identical meals (training meals) and a fourth meal with different content (validation meal). Energy intake was estimated by four different methods: weighed food records (gold standard), diet diaries, photographic food records, and CCS models. Counts of chews and swallows were measured using wearable sensors and video analysis. Results for the training meals demonstrated that CCS models presented the lowest reporting bias and a lower error as compared to diet diaries. For the validation meal, CCS models showed reporting errors that were not different from the diary or the photographic method. The increase in error for the validation meal may be attributed to differences in the physical properties of foods consumed during training and validation meals. However, this may be potentially compensated for by including correction factors into the models. This study suggests that estimation of energy intake from CCS may offer a promising alternative to overcome limitations of self-report. Fil: Fontana, Juan Manuel. University of Alabama; Estados Unidos. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Higgins, Janine A.. University of Colorado Anschutz Medical Center; Estados Unidos Fil: Schuckers, Stephanie C.. Clarkson University; Estados Unidos Fil: Bellisle, France. Universite de Paris 13-Nord; Francia Fil: Pan, Zhaoxing. University of Colorado Anschutz Medical Campus; Estados Unidos Fil: Melanson, Edward L.. University of Colorado Anschutz Medical Campus; Estados Unidos Fil: Neuman, Michael R.. Michigan Technological University; Estados Unidos Fil: Sazonov, Edward. University of Alabama; Estados Unidos

A microfabricated amperometric microcell was designed and used for the determination of proline iminopeptidase (PIP) enzyme activity in 2-10-microl samples. The measurements were made in the range of 10.3-841.5 mU/ml enzyme activities. The sensitivity of the determinations was between - 0.0195 and - 0.0203 microA ml/mU per min. The coefficient of variation of the determined values ranged between 2.8 (at 561.2 mU/ml) and 24.1% (at 10.3 mU/ml). The microcell was manufactured on an alumina substrate using screen-printed graphite working and Ag/AgCl reference electrodes. Elevated PIP activity in the vaginal fluid is a biochemical indicator of bacterial vaginosis. The method is appropriate to differentiate between normal (66+/-145 mU/ml) and elevated, diseased (704+/-145 mU/ml), values.

As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) we compared apnea identified by a customized home monitor using respiratory inductance plethysmography (RIP) with simultaneously recorded polysomnography-acquired nasal end-tidal CO2 (Pet CO2 ) and nasal/oral thermistor in 422 infants during overnight laboratory recordings to determine concordance between techniques, sources of disagreement, and capacity of RIP to detect obstructed breaths within an apnea. Among 233 episodes of apnea identified by at least one method as ⩾ 16 s, 120 were observed by the CHIME monitor, 219 by Pet CO2 , and 163 by thermistor. The positive predictive value of the CHIME-identified apnea was 89.2% (95% CI 83, 95) and 73% (95% CI 65, 81) for Pet CO2 and thermistor, respectively. However, the sensitivity of the CHIME monitor in identifying events detected by the other methods was only ∼ 50%. Among 87 apnea events identified by all three techniques, no two methods showed high agreement in measurement of apnea d...

There are numerous reports of cardiorespiratory patterns in infants on home monitors, but no data to determine whether "experts" agree on the description of these patterns. Therefore, we evaluated agreement among four experienced investigators and five trained technicians who assessed independently the same sample of physiologic waveforms recorded from infants enrolled in a multicenter study. The monitor used respiratory inductance plethysmography and recorded waveforms for apnea > or = 16 s or a heart rate or = 5 s. The investigators and technicians initially assessed 88 waveforms. After additional training, the technicians assessed another 113 additional waveforms. In categorizing waveforms as apnea present or absent, agreement among technicians improved considerably with additional training (kappa 0.65 to 0.85). For categorizing waveforms as having bradycardia present versus absent, the trends were the same. Agreement in measurement of apnea duration also improved considerably with additional training (intraclass correlation 0.33-0.83). Agreement in measurement of bradycardia duration was consistently excellent (intraclass correlation 0.86-0.99). Total agreement was achieved among technicians with additional training for measurement of the lowest heart rate during a bradycardia. When classifying apnea as including > or = 1, > or = 2, > or = 3, or > or = 4 out-of-phase breaths, agreement was initially low, but after additional training it improved, especially in categorization of apneas with > or = 3 or > or = 4 out-of-phase breaths (kappa 0.67 and 0.94, respectively). Although researchers and clinicians commonly describe events based on cardiorespiratory recordings, agreement amongst experienced individuals may be poor, which can confound interpretation. With clear guidelines and sufficient training raters can attain a high level of agreement in describing cardiorespiratory events.

This paper summarizes the discussions held during the First IEEE Life Sciences Grand Challenges Conference, held on October 4-5, 2012, at the National Academy of Sciences, Washington, DC, and the grand challenges identified by the conference participants. Despite tremendous efforts to develop the knowledge and ability that are essential in addressing biomedical and health problems using engineering methodologies, the optimization of this approach toward engineering the life sciences and healthcare remains a grand challenge. The conference was aimed at high-level discussions by participants representing various sectors, including academia, government, and industry. Grand challenges were identified by the conference participants in five areas including engineering the brain and nervous system; engineering the cardiovascular system; engineering of cancer diagnostics, therapeutics, and prevention; translation of discoveries to clinical applications; and education and training. A number of these challenges are identified and summarized in this paper.

To test the hypothesis that term-born Asian infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heart rate rhythm (CHR) at a later age than non-Asian term infants.Repeated overnight heart rate (HR) traces obtained with a battery-operated Polar S810i heart-rate monitor at home in 17 Asian Torajan infants in Indonesia, were compared with those of 52 non-Asian infants monitored as part of the Collaborative Home Infant Monitoring Evaluation (CHIME). HR was determined using a moving window averaging technique. A comparison of median HR during quiet sleep (QS) episodes (identified by minimum HR variability), established the presence of CHR.Seventy three percent of non-Asian CHIME infants ≤7 weeks exhibited CHR compared to 45% of Asian Torajan infants. Between 8 and 12 weeks, 94% of non-Asian CHIME infants exhibited CHR, compared to 33% of Asian Torajan infants (p0.001). Forty seven and 56% of Asian Torajan infants exhibited the CHR at the age intervals of 16-20 weeks and 21-25 weeks respectively. Active wakefulness percentages as a function of the entire recording and median QS HR were not significantly different in the two groups.Despite the fact that Asian Torajan infants were on average a week older than non-Asian CHIME babies, between two and three months of age only one in three exhibited the CHR, compared to virtually all non-Asian CHIME infants. We speculate that the cause of this difference rests in the infants' environment rather than their genetic origin.

Ion-sensitive, planar micro-electrode arrays were fabricated by photolithographic microelectronics technology on a flexible polyimide substrate. The steps of the microelectronics processing are summarized. The electrodes were tested in blood serum, whole blood and in the hamstring muscle of anesthetized rabbits. The performance characteristics of planar pH-sensors are compared with commercial glass electrodes. The close correlation of the data are encouraging for further acute and later chronic applications.

Our understanding of etiology of obesity and overweight is incomplete due to lack of objective and accurate methods for Monitoring of Ingestive Behavior (MIB) in the free living population. Our research has shown that frequency of swallowing may serve as a predictor for detecting food intake, differentiating liquids and solids, and estimating ingested mass. This paper proposes and compares two methods of acoustical swallowing detection from sounds contaminated by motion artifacts, speech and external noise. Methods based on mel-scale Fourier spectrum, wavelet packets, and support vector machines are studied considering the effects of epoch size, level of decomposition and lagging on classification accuracy. The methodology was tested on a large dataset (64.5 hours with a total of 9,966 swallows) collected from 20 human subjects with various degrees of adiposity. Average weighted epoch recognition accuracy for intra-visit individual models was 96.8% which resulted in 84.7% average weighted accuracy in detection of swallowing events. These results suggest high efficiency of the proposed methodology in separation of swallowing sounds from artifacts that originate from respiration, intrinsic speech, head movements, food ingestion, and ambient noise. The recognition accuracy was not related to body mass index, suggesting that the methodology is suitable for obese individuals.

Understanding of eating behaviors associated with obesity requires objective and accurate monitoring of food intake patterns. Accurate methods are available for measuring total energy expenditure and its components in free-living populations, but methods for measuring food intake in free-living people are far less accurate and involve self-reporting or subjective monitoring. We suggest that chews and swallows can be used for objective monitoring of ingestive behavior. This hypothesis was verified in a human study involving 20 subjects. Chews and swallows were captured during periods of quiet resting, talking, and meals of varying size. The counts of chews and swallows along with other derived metrics were used to build prediction models for detection of food intake, differentiation between liquids and solids, and for estimation of the mass of ingested food. The proposed prediction models were able to detect periods of food intake with >95% accuracy and a fine time resolution of 30 s, differentiate solid foods from liquids with >91% accuracy, and predict mass of ingested food with >91% accuracy for solids and >83% accuracy for liquids. In earlier publications, we have shown that chews and swallows can be captured by noninvasive sensors that could be developed into a wearable device. Thus, the proposed methodology could lead to the development of an innovative new way of assessing human eating behavior in free-living conditions.

A methodology of studying of ingestive behavior by non-invasive monitoring of swallowing (deglutition) and chewing (mastication) has been developed. The target application for the developed methodology is to study the behavioral patterns of food consumption and producing volumetric and weight estimates of energy intake. Monitoring is non-invasive based on detecting swallowing by a sound sensor located over laryngopharynx or by a bone conduction microphone and detecting chewing through a below-the-ear strain sensor. Proposed sensors may be implemented in a wearable monitoring device, thus enabling monitoring of ingestive behavior in free living individuals. In this paper, the goals in the development of this methodology are two-fold. First, a system comprised of sensors, related hardware and software for multimodal data capture is designed for data collection in a controlled environment. Second, a protocol is developed for manual scoring of chewing and swallowing for use as a gold standard. The multi-modal data capture was tested by measuring chewing and swallowing in twenty one volunteers during periods of food intake and quiet sitting (no food intake). Video footage and sensor signals were manually scored by trained raters. Inter-rater reliability study for three raters conducted on the sample set of 5 subjects resulted in high average intra-class correlation coefficients of 0.996 for bites, 0.988 for chews, and 0.98 for swallows. The collected sensor signals and the resulting manual scores will be used in future research as a gold standard for further assessment of sensor design, development of automatic pattern recognition routines, and study of the relationship between swallowing/chewing and ingestive behavior.

Reliability of classification performance is important for many biomedical applications. A classification model which considers reliability in the development of the model such that unreliable segments are rejected would be useful, particularly, in large biomedical data sets. This approach is demonstrated in the development of a technique to reliably determine sleep and wake using only the electrocardiogram (ECG) of infants. Typically, sleep state scoring is a time consuming task in which sleep states are manually derived from many physiological signals. The method was tested with simultaneous 8-h ECG and polysomnogram (PSG) determined sleep scores from 190 infants enrolled in the collaborative home infant monitoring evaluation (CHIME) study. Learning vector quantization (LVQ) neural network, multilayer perceptron (MLP) neural network, and support vector machines (SVMs) are tested as the classifiers. After systematic rejection of difficult to classify segments, the models can achieve 85%-87% correct classification while rejecting only 30% of the data. This corresponds to a Kappa statistic of 0.65-0.68. With rejection, accuracy improves by about 8% over a model without rejection. Additionally, the impact of the PSG scored indeterminate state epochs is analyzed. The advantages of a reliable sleep/wake classifier based only on ECG include high accuracy, simplicity of use, and low intrusiveness. Reliability of the classification can be built directly in the model, such that unreliable segments are rejected.

We investigated the effects of prenatal cocaine exposure (PCE) on heart rate (HR) and heart rate variability (HRV) in the presence of orthostatic stress among near- and full-term neonates. PCE infants (n = 21) and controls (n = 23) were enrolled within 120 h of birth. ECG was recorded for an hour during quiet sleep, 30 min in supine position and then 30 min in an inclined position. Linear mixed models were used to analyze HR and HRV in the time domain and wavelet and power spectrum analyses in the frequency domain. PCE infants had tachycardia both before (p = 0.091) and after tilting (p = 0.015), but with a clear interaction between PCE and orthostatic stress (p = 0.049). Compared with controls, PCE infants had a delayed and prolonged reaction to orthostatic stress. There was also a pronounced interaction with regard to log-transformed SDDRR, a measure of HRV (p = 0.049). Controls experienced an instantaneous increase in log (SDDRR) followed by a prompt return to normal levels, while PCE infants had a gradual increase that did not dissipate quickly. Frequency-domain analyses also distinguished between the cocaine-exposed infants and the controls. Results suggest that the effects of PCE on the development of sympathetic and parasympathetic systems could lead to altered cardiovascular function.

ContextHome monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven.ObjectiveTo test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants.DesignLongitudinal cohort study conducted from May 1994 through February 1998.SettingFive metropolitan medical centers in the United States.ParticipantsA total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing.Main Outcome MeasuresOccurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors.ResultsDuring 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age.ConclusionsIn this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.

We used in vivo magnetic resonance (MR) microscopy to follow the growth of fibrous capsule as a foreign body reaction to silicone implants in rats. Anesthetized rats were imaged 1, 7, 14, and 28 days after silicone-coated MR imaging coils were sutured to their neck muscles. On the twenty eighth day, rats were sacrificed and coils and adjacent tissues were removed en bloc and fixed in formalin, reimaged with MR, and sectioned for conventional histology. Three-dimensional (3-D) spin-echo [3DFT] acquisition gave in-plane resolution of 32/spl times/32 /spl mu/m in vivo and 16/spl times/16 /spl mu/m ex vivo. All MR images showed a diffuse band of elevated signal intensity between the silicone of the coil and adjacent tissue. The border of the hyperintense band was thin and not well defined at seven days post-implantation. From 7-28 days, the band showed relatively homogeneous signal intensity and its thickness increased 44% on the rectus muscle side and 78% on the subcutaneous side. The capsule thickness determined either by MR in vivo and ex vivo microscopy or conventional histology was not significantly different, and there was a significant correlation between thickness measurements among those methods. MR in vivo microscopy provides sufficient resolution and spatial information to serially evaluate the growth of the foreign body fibrous capsule over time, thus achieving greater accuracy and consistency in measurements.

Background As part of the Collaborative Home Infant Monitoring Evaluation, a home monitor was developed to record breathing, heart rate, other physiologic variables, and the time the monitor was used. Objective To determine the frequency of monitor use, factors that influence use, and validity of a model developed to predict use. Design We developed a model to predict monitor use using multiple linear regression analysis; we then tested the validity of this model to predict adherence for the first week of monitoring and for the subsequent 4-week period (weeks 2-5). Setting Clinical research centers in Chicago, Ill; Cleveland, Ohio; Honolulu, Hawaii; Los Angeles, Calif; and Toledo, Ohio. Patients Preterm infants, infants younger than 1 month with a history of autopsy-confirmed sudden infant death syndrome in a sibling, and infants with an idiopathic apparent life-threatening event were divided into 2 cohorts based on enrollment date. Main Outcome Measure Mean hours of monitor use per week. Results In cohort 1, the variables available before monitoring were only weakly associated with total hours of monitor use in weeks 2 to 5 (total model r 2 = 0.08). However, when hours of monitor use in week 1 were included as a variable to predict monitor use in weeks 2 to 5, the r 2 increased to 0.64 for hours of monitor use per week. Conclusions Our data show that monitor use in the first week was the most important variable for predicting subsequent monitor use. The study suggests that a major focus of home monitoring should be adherence in the first week, although it remains to be tested whether this adherence can be altered.

Five methods have been developed to process output signals from sensor arrays to improve sensor characteristics. A multielement capacitive force sensor array with nonlinear characteristics and inter-element cross-talk was used to demonstrate and compare the performance of these methods: (1) Variable Threshold, which calculated a threshold value from a histogram of the data to determine whether the output of each element was due to an input or cross-talk; (2) Algebraic Cross-Talk Reduction, which reduced the cross-talk between array elements by solving for the input matrix from the input-output relation of the sensor; (3) 2 x 2 Edge and Shape Detection, which was adapted from image processing techniques and enhanced the resolution of the sensor output; (4) Deconvolution using FFT; and (5) Artificial Neural Network, which was trained to learn the inverse relation of the sensor transfer function. The ability of these methods to reduce the cross-talk seen between sensor elements and more closely estimate the sensor input was studied. Preprocessing of the sensor output, which consisted of calibration of each element using non-linear curve fitting, was used to compensate for the non-linear, non-uniform sensitivity characteristics of the sensor array elements. Postprocessing compensated for the dependency on the number of excited elements. A comparative study of eight force sensor arrays using a 200 element test set showed that the simpler signal processing methods, Variable Threshold and 2 x 2 Edge and Shape Detection, performed well only for a limited number of input conditions especially when forces were applied through small objects. In general, neither reduced the error in determining total force by more than 30 percent. The Artificial Neural Network method, the most complicated and computationally intensive method during initial training but simple to implement thereafter, produced superior results for the majority of the input patterns applied to the sensor array, reducing the overall error by 6 to 83 percent. All five signal processing techniques reduced the overall errors of the sensor outputs, some more consistently than others. However, when the overall error magnitude was less than 10 percent, only the Artificial Neural Network reduced the error consistently, making it the method of choice. The results of this study showed that sensors having outputs with high error values can be converted into sensors with much lower output error using appropriate signal processing methods. Incorporation of such signal processing methods into sensor arrays allows the use of sensors with less than ideal characteristics.

Respiratory center drive is most accurately reflected from the steepest rise of the diaphragmatic EMG (Edi) at inspiratory onset. This parameter equates to peak acceleration of diaphragmatic activation (PaEdi) and reflects diaphragmatic recruitment whereas further rise of Edi amplitude (EdiA) signifies continued neuronal discharge. Calibrated respiratory inductive plethysmography (RIP) provides rib cage (RC), abdominal (AB) and their sum(Vt) waveforms noninvasively. We therefore tested the hypothesis that RIP derived acceleration signals (PaRC, PaAB or PaVt) could be used as measures of respiratory drive by validation with PaEdi during unimpeded breathing and obstructed efforts. Five newborn piglets were lightly anesthetized and allowed to breathe spontaneously through cuffed endotracheal tubes. A wire electrode was inserted into the diaphragm using a percutaneous, subcostal approach and RIP transducers applied to the RC and AB compartments. Peak acceleration from RIP waveforms was measured as the highest value in a window range of±300 msec around the mechanical onset of inspiration. The same window was used for PaEdi. Data were displayed and stored on a Respitrace PT16 recorder (Nims, Miami Beach, FL) for subsequent analysis with RespiEvents software. Interventions included 7% CO2 rebreathing and end expiratory obstruction of the endotracheal tube over 2-4 efforts. For CO2 rebreathing, a correlation matrix was calculated for each animal and the means(SD) are listed below; *indicates r with p

Although there are numerous reports of cardiorespiratory patterns in infants on home monitors, there are no data to determine if experts actually agree on the description of these patterns. To assess agreement among observers in describing cardiorespiratory variables, four senior investigators and five trained technicians each independently assessed physiologic tracings recorded in the homes of 18 infants enrolled in a multicenter study. The monitor utilized respiratory inductance plethysmography and recorded a tracing(75 s. preceding the onset and 30 s. following resolution of events) whenever it detected apnea ≥16 s. or a heart rate 0.90 for technicians). Agreement in measurement of apnea duration was initially relatively low (intra-class correlation (ICC) 0.33), but following additional training ICC increased to 0.83. Agreement in measurement of bradycardia duration was consistently excellent (ICC 0.86-0.99). Agreement in measurement of the lowest heart rate during a bradycardia was better for technicians than investigators (ICC 0.77 vs. 0.65). With additional training there was total agreement among technicians (ICC 1.0). When classifying apnea as including ≥1, ≥2 or≥3 out-of-phase breaths, agreement was low for investigators (kappas 0.33, 0.22 and 0.11), while the technicians following training were able to achieve better agreement especially in categorization of apneas with ≥3 out-of-phase breaths (kappa 0.67). While researchers and clinicians commonly describe events based on cardiorespiratory recordings, agreement amongst experienced individuals may be poor. This lack of agreement between experts may seriously impair comparison of studies and mandates careful definition of variables, intensive training and demonstrated reliability in the conduct of studies. (NICHD HD 29067 29071 28971 29073 29060 29056 34625)

Apnea duration: Respiratory Inductance Plethysmography (RIP) and Transthoracic Impedance (TTI) Pneumography vs. Polysomnography (PSG) † 1791

Longitudinal Assessment of Oxygen Saturation and Sleep Position in Healthy Term Infants During the First 6 Months of Life † 1180

Low-power miniature switching circuits for controlling the power supply to an implanted electronic circuit are described. These circuits can be used as power supply switches for conserving battery power on implanted systems. Monostable and bistable switches that can be triggered either by radio-frequency energy or light are presented. Circuits, having standby currents as low as 25 nA and operated at voltages of 1.35 V, are described. A hybrid microelectronics realization of a radio-frequency triggered bistable switch is described. Radio-frequency triggering by induction can be carried out over distances ranging from 2 to 10 cm, depending on the circuit used. Light triggering using either electronic photoflash lamps or low-power incandescent lights can be achieved over distances as great as 250 cm.

MORE than 200 years ago, our forefathers made note of man's inalienable rights to life, liberty, and the pursuit of happiness. To the engineering community (applied science in the service of man), these may be coincident with applications to medicine and biology (biomedical engineering), defense, and entertainment. Biomedical engineering research has the distinction, among these three missions, of not only contributing to the quality of human life through the industrial economy but also to life itself - the most fundamental concern of all people. It is through biomedical engineering research that we have been able to learn much concerning the functioning of living systems, and it is through such knowledge that we have been able to develop improved clinical diagnosis, monitoring, and treatment, including life-sustaining devices and aids to the handicapped. Each step represents an improvement in the quality of life, and each step forms the foundation upon which to gain new knowledge to improve upon earlier developments.

Thin-film microelectronic technology was used to fabricate a miniature, flexible sensor that can be placed directly onto the surface of the airway to measure the electrical conductance of the fluids present. Gold was deposited on glass, oxidized silicon, and polyimide substrates. The parallel gold electrodes were etched into an interdigitated configuration that increased the effective sensing area without increasing the sensor size. A temperature-sensitive resistor was added to make calculations possible to account for the effect of temperature on fluid conductivity. Fluid conductivity was measured and from this information osmolarity was calculated. Physiologic evaluation of the device and corroboration of the calculations was obtained by placing the sensor in the airway of mongrel dogs and simultaneously collecting surface fluids for atomic absorption spectroscopy and freezing-point-depression analysis. Osmolarity calculations made from the sensor data were consistently about 25% lower than clinical laboratory osmolarity analysis. In vitro tests of the sensor included calibration in multiple dilute salt solutions, temperature sensitivity assessment, and evaluation of the effects of solution concentration on electrical conductance. >

Palladium-palladium oxide film formed by the RF reactive sputtering technique was used for pH measurement. The potentiometric mode of operation was employed and an Ag/AgCl electrode was used as the reference electrode. The Pd-PdO film was formed on both alumina and polycrystalline silicon, and sputtering conditions to produce Pd-PdO film with good pH response characteristics were empirically defined. The Pd-PdO showed good pH response, ~54 mV/[pH] at 25 °C over the pH range of 3-9. The temperature dependency and dissolved oxygen effect on the film when used as a pH sensor were investigated and discussed.

Miniature antimony–antimony oxide sensors have been used to record intraesophageal pH during diagnostic esophageal manometry. The electrodes have a rapid response time and sufficient accuracy and reproducibility to give good assessment of gastroesophageal reflux. The electrodes are durable and have a very low impedance (

Three relatively simple devices for improving safety in neonatal intensive care are described. When umbilical artery catheters are used, an inexpensive pressure switch is utilized to detect abnormally low pressures associated with catheter withdrawal or excessive fluid leakage from the catheter system. A capacitive, intravenous-line air bubble detector, consisting of a section of the intravenous line as the dielectric of a capacitor, is used to alert the clinical staff when air bubbles pass between the capacitor plates. An electronic temperature controller maintains the temperature of neonatal breathing gases to avoid temperature variations which occur with presently used techniques. These are relatively simple and inexpensive devices which can be fabricated by most hospital clinical engineering services.

Medical devices and medical electronics are areas that had little to offer 100 years ago. However, there were three important existing technologies that led to many further developments over the following 100 years. These are the stethoscope, electrocardiography, and X-ray medical imaging. Although these technologies had been described and were available to some extent when the Proceedings of the IEEE pages first appeared, they had yet to achieve the widespread use that they have today. The stethoscope is the oldest of these, and it helped physicians to hear sounds of the body and relate them to functioning and malfunctioning organs. The early use of the stethoscope by physicians was more of an art than a science, but as the Proceedings matured, so did this technology. Engineers were able to make this a more quantitative process by graphically displaying the sounds and ultimately using techniques such as voiceprint analysis to assist the physician in diagnosis and monitoring of treatment. The electrocardiograph had been invented a few years prior to the appearance of the Proceedings, but the apparatus was awkward to use, especially for sick people, and was considered more of an oddity than a viable medical technology 100 years ago. Today, it and devices derived from it such as cardiac patient monitors are important parts of our healthcare system. Similarly, X-rays represented a new technology 100 years ago, but unlike electrocardiography physicians immediately saw the value of this technology and quickly adopted it. Many improvements have been made to the basic technology over the last 100 years culminating in computer tomography and complex image processing. Other devices to create high-quality and 3-D medical images have also been developed in recent years to make medical imaging a very important aspect of clinical care today. Looking to the future is always a difficult task, but it is clear that the electronic health record will play an important role in consolidating the information from various medical devices as well as providing readily available data on patients wherever it might be needed. Future medical devices will need to not only address the problems of diagnostic and therapeutic medicine but also be capable of addressing important societal problems such as worldwide disparities in the availability of medical care, continually rising healthcare costs, and healthcare for travel beyond Earth. The next 100 years promises to be even more exciting than the last from the perspective of medical devices and medical electronics.

A wire-form miniature palladium-palladium oxide electrode has been fabricated for pH measurement. The electrode exhibits a super-Nernstian behavior and gives a mean pH response of 71.4 millivolts per [pH] (standard deviation, 5.2 millivolts). Uncorrected zero current potential values can be used to determine the pH value of the medium to within 0.012 pH. The electrode should find applications in biological, medical, and clinical studies.