A Palladium-palladium oxide miniature pH electrode.

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.

Energy scavenging sources for biomedical sensors.

Energy scavenging has increasingly become an interesting option for powering electronic devices because of the almost infinite lifetime and the non-dependence on fuels for energy generation. Moreover, the rise of wireless technologies promises new applications in medical monitoring systems, but these still face limitations due to battery lifetime and size. A trade-off of these two factors has typically governed the size, useful life and capabilities of an autonomous system. Energy generation from sources such as motion, light and temperature gradients has been established as commercially viable alternatives to batteries for human-powered flashlights, solar calculators, radio receivers and thermal-powered wristwatches, among others. Research on energy harvesting from human activities has also addressed the feasibility of powering wearable or implantable systems. Biomedical sensors can take advantage of human-based activities as the energy source for energy scavengers. This review describes the state of the art of energy scavenging technologies for powering sensors and instrumentation of physiological variables. After a short description of the human power and the energy generation limits, the different transduction mechanisms, recent developments and challenges faced are reviewed and discussed.

Fabrication of miniature PO2 and pH sensors using microelectronic techniques.

Miniature PO2 and pH sensors can be used in combination with enzymatic catalysts such as glucose oxidase and glucose dehydrogenase as the basis for the development of a small glucose sensor. The applications of microelectronic techniques such as photolithography techniques and thick- and thin-film metallization are novel approaches in fabricating highly uniform and reproducible sensors that are relatively simple to calibrate and operate.

Improvement of the Botstein-Zacharopolous radiation applicator.

The Botstein-Zacharopolous afterloading radiation source has been modified to facilitate its application to patients receiving intracavitary irradiation therapy. A new clamp assembly, in which each ovoid and the tandum can be separately controlled, has been designed and implemented. A study of 74 patients who alternately received the original or the modified applicator showed the time of the application procedure to be significantly less (p less than 0.001) with the modified device than it was with the original instrument. Fewer X rays were required for evaluating the placement of the modified instrument than the original applicator (p = .055).

Infant polysomnography: reliability. Collaborative Home Infant Monitoring Evaluation (CHIME) Steering Committee.

Infant polysomnography (IPSG) is an increasingly important procedure for studying infants with sleep and breathing disorders. Since analyses of these IPSG data are subjective, an equally important issue is the reliability or strength of agreement among scorers (especially among experienced clinicians) of sleep parameters (SP) and sleep states (SS). One basic issue of this problem was examined by proposing and testing the hypothesis that infant SP and SS ratings can be reliably scored at substantial levels of agreement, that is, kappa (kappa) > or = 0.61. In light of the importance of IPSG reliability in the collaborative home infant monitoring evaluation (CHIME) study, a reliability training and evaluation process was developed and implemented. The bases for training on SP and SS scoring were CHIME criteria that were modifications and supplements to Anders, Emde, and Parmelee (10). The kappa statistic was adopted as the method for evaluating reliability between and among scorers. Scorers were three experienced investigators and four trainees. Inter- and intrarater reliabilities for SP codes and SSs were calculated for 408 randomly selected 30-second epochs of nocturnal IPSG recorded at five CHIME clinical sites from healthy full term (n = 5), preterm (n = 4), apnea of infancy (n = 2), and siblings of the sudden infant death syndrome (SIDS) (n = 4) enrolled subjects. Infant PSG data set 1 was scored by both experienced investigators and trained scorers and was used to assess initial interrater reliability. Infant PSG data set 2 was scored twice by the trained scorers and was used to reassess inter-rater reliability and to assess intrarater reliability. The kappa s for SS ranged from 0.45 to 0.58 for data set 1 and represented a moderate level of agreement. Therefore, rater disagreements were reviewed, and the scoring criteria were modified to clarify ambiguities. The kappa s and confidence intervals (CIs) computed for data set 2 yielded substantial inter-rater and intrarater agreements for the four trained scorers; for SS, the kappa = 0.68 and for SP the kappa s ranged from 0.62 to 0.76. Acceptance of the hypothesis supports the conclusion that the IPSG is a reliable source of clinical and research data when supported by significant kappa s and CIs. Reliability can be maximized with strictly detailed scoring guidelines and training.

Determination of the elastic properties of the cervix.

The elastance of the uterine cervix of nonpregnant women was measured by placing a 3- or 4-cm compliant balloon in the cervical canal and determining its pressure-volume characteristic while filling with up to 5 mL of sterile water at a rate of 12 mL/minute. The mean elastance for 247 patients who had previously suffered either one or more spontaneous midterm pregnancy losses, preterm birth, or three or more early spontaneous abortions was significantly lower than that of 42 controls who did not meet these criteria. Elastances were significantly lower in groups having a clinically observed patulous cervix or laceration, or a clinically diagnosed incompetent cervix, than in the normal cervix group. No significant difference was found between the follicular and luteal phases for 64 regularly cycling women. Values were significantly reduced in women showing a widened cervix on a hysterosalpingogram when compared with those with a normal-appearing cervix. When larger Hegar dilators were passed without resistance, the elastance was generally lower, although there was not always good correlation between the largest dilator passed and elastance.

Evaluation of fetal monitoring by telemetry.

A radiotelemetry system for the direct monitoring of fetal heart rate and intrauterine pressure during labor has been evaluated at 5 different institutions. A conventional fetal scalp electrode and a special intrauterine pressure sensor are connected to a radio transmitter placed on the patient's thigh. The receiver can be located up to 50 feet away from the transmitter and is either a self-contained monitor or a unit that converts a conventional fetal monitor to a telemetric one. The telemetry recordings are of similar quality to those obtained from conventional monitors. Telemetry allows for greater patient comfort and mobility as well as greater convenience to the clinical staff. Continuous data can be obtained from patients while they are ambulatory or sitting in a chair as well as while they are in bed.

Screen-printed amperometric microcell for proline iminopeptidase enzyme activity assay.

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.

The neonatal oxycardiorespirogram.

The neonatal oxycardiorespirogram is the simultaneous recording of respiration rate, respiration waveform, instantaneous heart rate, transcutaneous oxygen tension, and relative skin perfusion or "blood flow" from newborn infants. It is important in monitoring the high risk infant to assess the cardiovascular and respiratory function of the patient. The techniques for obtaining the various signals of the oxycardiorespirogram are reviewed and the usual method for making this recording is presented. Several examples of typical oxycardiorespirograms are given.

Effect of infant position on breath amplitude measured by transthoracic impedance and strain gauges.

Continuous monitoring of respiration by transthoracic electrical impedance gives a signal that has certain not well understood irregularities. Among them is a change in the amplitude of the signal when there is no apparent change in the infant's tidal respiration. One factor that could hypothetically account for alterations of the impedance signal is a change in current path through the thorax secondary to a change in body position. To test this hypothesis we have studied the relationships between breath amplitude measured by transthoracic impedance, one strain gauge on the chest and one on the abdomen, and tidal volume by integrated flow in four body positions. Median breath amplitude was found to vary significantly with body position according to the measuring device. The median impedance breath amplitude increased by 27% in the supine position compared with the prone position, with no associated change in tidal volume. Differences in the strain gauge signal amplitude for these positions were not statistically significant. Correlation between breath amplitude measured by impedance changes and tidal volume was minimal (r = 0.114). These results indicate that infant position affects impedance breath amplitude independently of changes in tidal volume.

Optimal electrode location for monitoring the ECG and breathing in neonates.

Continuous monitoring of breathing in infants is commonly performed using transthoracic impedance. This method employs skin surface electrodes measuring changes in electrical impedance and relates these changes to respiratory events. Typically, two electrodes on the infant's chest monitor both the ECG and breathing. We have attempted to identify separate electrode locations that give the best signal for breathing and ECG, and a single location that optimizes both of these signals. Thirty-seven infants were studied by placing 12 electrodes on the infant's chest and abdomen, and serially sampling pairwise combinations of electrodes. The optimal signal for breathing was obtained when electrodes spanned the diaphragm. Optimal ECG signal was seen with one electrode at the right mid-clavicle and one at the xyphoid. Clinicians should be aware of these locations in order to provide the best signal available.

Measuring the progression of foreign-body reaction to silicone implants using in vivo MR microscopy.

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 x 32 microns in vivo and 16 x 16 microns 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.

Planar micro sensors for in vivo myocardial pH measurements.

Potentiometric responses of microelectronically fabricated planar pH sensors based on both TDDA or ETH 5294 proton neutral carriers, in aminated PVC matrix, were evaluated with respect to main analytical parameters (linear ranges, slopes, reproducibility of potential measurements, potential drift and membrane resistance). In order to increase the electrode life time, increased amounts of membrane material were applied on the Ag/AgCl-poly-HEMA active spots of the polyimide substrate. The electrodes were implanted into an in situ porcine beating heart preparation at a midmyocardial depth in order to monitor H(+) concentration changes during the course of coronary artery occlusion.

Aliphatic polyurethane as a matrix for pH sensors: effects of native sites and added proton carrier on electrical and potentiometric properties.

The potentiometric and impedance characteristics of polymeric membranes, based on aliphatic polyurethane (Tecoflex) as a matrix, are described and interpreted by theory and experiments for H(+) and alkali metal ion-sensitive sensors. Both dummy plasticized membranes and proton carrier-loaded membranes can show pH response. The pH response of dummy membranes is due to protonated natural negative sites in the polyurethane matrix. The electrodes with added proton carrier show improved rejection of Li(+), Na(+), and K(+) responses and give useful analytical responses. Optimal performance requires control of negative site concentration by addition of lipophilic salt (e.g. tetraphenylborate derivatives). Impedance analyses show surface-rate semicircles and, depending on the bathing electrolyte solution, appearance of a diffusional Warburg impedance. In addition to these time-dependence surface region effects, changes in the bulk membrane resistance with soaking time can be well correlated with equilibrium water content of plasticized membranes.

Amperometric measuring cell for the determination of putrescine oxidase activity.

A microfabricated, flat form, amperometric microcell (microchip) is used in a simple, two-electrode arrangement for putrescine oxidase enzyme activity determinations. The cell contains a platinum microdisk working electrode and an Ag/AgCl reference electrode covered by a porous, hydrophilic membrane. An electrochemically-prepared size-exclusion layer is applied on the working electrode surface, to avoid the effect of electroactive interferences in the sample. The hydrophilic membrane, resting on the bottom of the cell, is soaked with a small volume of buffered substrate solution and a few mul enzyme containing sample solution is dispensed over the electrodes. During the enzyme activity measurement a catalytic reaction takes place in the membrane-supported liquid film over the working electrode surface. The hydrogen peroxide produced in the reaction is detected amperometrically. The amperometric current-time curves are used for evaluation. In our work putrescine was used as a substrate to determine the unknown putrescine oxidase enzyme activity of the sample. Elevated diamine oxidase enzyme activity in the vaginal milieu can indicate premature rupture of the amniotic membrane. Results with membrane discs, containing all the necessary chemicals in solid or lyophilized form, are very encouraging with respect of a single use, 'reagentless' biosensor for home care.

Development of a diamine biosensor.

An amperometric diamine sensor is developed for clinical applications in diagnosis of bacterial vaginosis (BV). The sensor is based on crosslinked putrescine oxidase (PUO) which catalyzes the conversion of diamines (mainly putrescine and cadaverine) to products including hydrogen peroxide. The hydrogen peroxide is detected anodically at platinum electrode polarized at 0.5 V versus Ag/AgCl. Platinum-plated gold electrodes used as a substrate for the sensor construction, are batch-fabricated on a flexible polyimide foil (Kapton(R), DuPont). A three-electrode cell configuration is used in all amperometric measurements. The sensor construction is based on three layers: an inner layer to reject the interference effect of oxidizable molecules, an outer diffusion controlling layer, and in addition, an enzyme middle layer. The enzyme layer was immobilized by crosslinking PUO with bovine serum albumin (BSA) using glutaraldehyde (GA). An optimization study of the enzyme solution composition was carried out. With the optimized enzyme layer, the biosensor showed a very high sensitivity and fast response time of ca. 20 s. The sensor has a linear dynamic range from (0.5-300 muM) for putrescine that covers the expected biological levels of the analyte. Details on sensor fabrication and characterization are given in the present work.

Thirty years of fetal and neonatal physiologic measurements. Have they made a difference?

In looking at fetal and neonatal measurement technology as covered in this issue and as reported in areas not covered in this issue, we need to ask the question: Has this technology made a difference? Unfortunately, the answer is not clear. There are cases where the answer is a solid "yes" and other cases where "maybe" is the best we can say at the present time. There are also a few examples where even though noble attempts have been made, the answer must be "no." What does this mean in terms of what needs to be done? We certainly need to continue the development of new measurement technology and to carry out this development based on sound physiologic and engineering principles. We need to understand better the physical and biologic basis of the measurements that we make and to perform carefully controlled clinical trials of technology before bringing it to the marketplace. Data presentation and archiving is an important issue that, although it is being addressed today, still has future implications as the amount of data increase. Finally, we must not forget the importance of our ultimate goal of helping families to have healthy, happy offspring.

Pulse oximetry: physical principles, technical realization and present limitations.

Oximetry for continuous patient monitoring has evolved to a mature technology that is clinically useful. Technologic limitations, however, still exist and there is need to develop more reliable, less expensive systems that will allow new applications such as fetal and home infant and adult monitoring. Although it is not possible to fully monitor patient blood gas status with a single variable, pulse oximetry provides an important view of the blood oxygen content that can be combined with other monitoring methods to more fully characterize patient status.

Estimation of the determinants of transcutaneous oxygen tension using a dynamic computer model.

A dynamic model for oxygen transport within the outer layers of the skin and a tcPO2 sensor has been developed. By comparing model simulations with clinical measurements from adults, it is possible to analyze some of the physiologic and physical determinants of the tcPO2 measurement. The results indicate that the permeability of the epidermis is a significant parameter when using a microcathode sensor. Using this model, the values obtained for normalized stratum papillare blood flow and metabolic oxygen consumption of the dermis are higher than those seen for other models.