Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring

The development and analytical characterization of a novel ion-selective potentiometric cell in a temporary-transfer tattoo platform for monitoring ammonium levels in sweat is presented. The fabrication of this skin-worn sensor, which is based on a screen-printed design, incorporates all-solid-state potentiometric sensor technology for both the working and reference electrodes, in connection to ammonium-selective polymeric membrane based on the nonactin ionophore. The resulting tattooed potentiometric sensor exhibits a working range between 10(-4) M to 0.1 M, well within the physiological levels of ammonium in sweat. Testing under stringent mechanical stress expected on the epidermis shows that the analytical performance is not affected by factors such as stretching or bending. Since the levels of ammonium are related to the breakdown of proteins, the new wearable potentiometric tattoo sensor offers considerable promise for monitoring sport performance or detecting metabolic disorders in healthcare. Such combination of the epidermal integration, screen-printed technology and potentiometric sensing represents an attractive path towards non-invasive monitoring of a variety of electrolytes in human perspiration.

BACKGROUND:Intraoperative hypotension is associated with postoperative mortality. Early detection of hypotension by continuous hemodynamic monitoring might prompt timely therapy, thereby reducing intraoperative hypotension. We tested the hypothesis that continuous noninvasive blood pressure monitoring reduces intraoperative hypotension.METHODS:Patients ≥45 years old with American Society of Anesthesiologists physical status III or IV having moderate-to-high-risk noncardiac surgery with general anesthesia were included. All participating patients had continuous noninvasive hemodynamic monitoring using a finger cuff (ClearSight, Edwards Lifesciences, Irvine, CA) and a standard oscillometric cuff. In half the patients, randomly assigned, clinicians were blinded to the continuous values, whereas the others (unblinded) had access to continuous blood pressure readings. Continuous pressures in both groups were used for analysis. Time-weighted average for mean arterial pressure <65 mm Hg was compared using 2-sample Wilcoxon rank-sum tests and Hodges Lehmann estimation of location shift with corresponding asymptotic 95% CI.RESULTS:Among 320 randomized patients, 316 were included in the intention-to-treat analysis. With 158 patients in each group, those assigned to continuous blood pressure monitoring had significantly lower time-weighted average mean arterial pressure <65 mm Hg, 0.05 [0.00, 0.22] mm Hg, versus intermittent blood pressure monitoring, 0.11 [0.00, 0.54] mm Hg (P = .039, significance criteria P < .048).CONCLUSIONS:Continuous noninvasive hemodynamic monitoring nearly halved the amount of intraoperative hypotension. Hypotension reduction with continuous monitoring, while statistically significant, is currently of uncertain clinical importance.

Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.

BackgroundFailure to recognize acute deterioration in hospitalized patients may contribute to cardiopulmonary arrest, unscheduled intensive care unit admission and increased mortality.PurposeIn this systematic review we aimed to determine whether continuous non-invasive respiratory monitoring improves early diagnosis of patient deterioration and reduces critical incidents on hospital wards.Data SourcesStudies were retrieved from Medline, Embase, CINAHL, and the Cochrane library, searched from 1970 till October 25, 2014.Study SelectionElectronic databases were searched using keywords and corresponding synonyms ‘ward’, ‘continuous’, ‘monitoring’ and ‘respiration’. Pediatric, fetal and animal studies were excluded.Data ExtractionSince no validated tool is currently available for diagnostic or intervention studies with continuous monitoring, methodological quality was assessed with a modified tool based on modified STARD, CONSORT, and TREND statements.Data SynthesisSix intervention and five diagnostic studies were included, evaluating the use of eight different devices for continuous respiratory monitoring. Quantitative data synthesis was not possible because intervention, study design and outcomes differed considerably between studies. Outcomes estimates for the intervention studies ranged from RR 0.14 (0.03, 0.64) for cardiopulmonary resuscitation to RR 1.00 (0.41, 2.35) for unplanned ICU admission after introduction of continuous respiratory monitoring,LimitationsThe methodological quality of most studies was moderate, e.g. ‘before-after’ designs, incomplete reporting of primary outcomes, and incomplete clinical implementation of the monitoring system.ConclusionsBased on the findings of this systematic review, implementation of routine continuous non-invasive respiratory monitoring on general hospital wards cannot yet be advocated as results are inconclusive, and methodological quality of the studies needs improvement. Future research in this area should focus on technology explicitly suitable for low care settings and tailored alarm and treatment algorithms.

Cardiovascular disease (CVD) is a prevalent cause of early mortality globally. Blood pressure (BP), a physiological indicator closely associated with CVD, facilitates early prevention and intervention of CVD by continuous monitoring, therefore significantly decreasing mortality rates and treatment expenses linked to CVD. Recently, wearable and non-contact continuous BP monitoring technologies have attracted considerable attention from both the academic community and industry. This review article summarizes the development status of current BP measurement research and highlights these continuous BP monitoring technologies across diverse anatomical sites, with particular emphasis on emerging sensor design methodologies and innovative research concepts. Sensors are generally categorized into photoelectric, pressure, bioimpedance, ultrasonic, accelerometric, and radar sensing technologies based on their sensing principle, with a concise overview of the measurement mechanism and application conditions for each kind provided. In addition, this review delineates the major measurement sites of existing continuous BP monitoring equipment and the application of key sensing technologies at these sites. The measurement locations cover major anatomical sites, including the fingers, wrist, upper arm, chest, face, and neck, as well as minor sites such as the superficial temporal artery, ears, and feet. While wearable devices are mainly positioned on the wrists and fingers, non-contact measurement methods are primarily applied to the head, neck, and chest. By systematically summarizing and analyzing the development of continuous BP monitoring technology across different body sites and considering the research direction of the integration of multi-modal sensing technology, we aim to provide a comprehensive perspective for this research area with the objective of developing practical and reliable continuous BP monitoring systems.

Digital Medicine and the Scripps Translational Science Institute

Currently, non-invasive continuous blood glucose monitoring technology remains insufficient in terms of clinical validation data. Existing approaches predominantly depend on statistical models to predict blood glucose levels, which often suffer from limited data samples. This leads to significant individual differences in non-invasive continuous glucose monitoring, limiting its scope and promotion. We propose a neural network that uses metabolic characteristics as inputs to predict the rate of insulin-facilitated glucose uptake by cells and postprandial glucose gradient changes (glucose gradient: the rate of change of blood glucose concentration within a unit of time (dG/dt), with the unit of mg/(dL × min), reflects the dynamic change trend of blood glucose levels). This neural network utilises non-invasive continuous glucose monitoring method based on the Bergman minimal model (BM-NCGM) while considering the effects of the glucose gradient, insulin action, and the digestion process on glucose changes, achieving non-invasive continuous glucose monitoring. This work involved 161 subjects in a controlled clinical trial, collecting over 15,000 valid data sets. The predictive results of BM-NCGM for glucose showed that the CEG A area accounted for 77.58% and the A + B area for 99.57%. The correlation coefficient (0.85), RMSE (1.48mmol/L), and MARD (11.51%) showed an improvement of over 32% compared to the non-use of BM-NCGM. The dynamic time warping algorithm was used to calculate the distance between the predicted blood glucose spectrum and the reference blood glucose spectrum, with an average distance of 21.80, demonstrating the excellent blood glucose spectrum tracking ability of BM-NCGM. This study is the first to apply the Bergman minimum model to non-invasive continuous blood glucose monitoring research, supported by a large amount of clinical trial data, bringing non-invasive continuous blood glucose monitoring closer to its true application in daily blood glucose monitoring. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR1900028100.

Wearable sensors with a non-invasive platform have garnered significant interest over the recent years in the area of personalised healthcare monitoring. Extensive research is being carried out in this field as it utilizes recent technology for the fabrication of smart sensors which aims in addressing the demands of epidermal sensing where durability, lightweight, and intimated skin conformance are core requirements. Yet, further progress in this area has been hindered due to the lack of efficient chemical sensors and biosensors, able to monitor the chemical constituents residing on the epidermis of the wearer’s body. In this context, electrochemical sensors offer promise as wearable chemical sensors due to their high performance, inherent miniaturization and low cost. A wide range of electrochemical sensors and biosensors have been developed for real-time non-invasive monitoring of electrolytes and metabolites in sweat, tears, saliva as indicator of wearer’s health status. Substantial progress in this field of electrochemical sensors has led to the development of commercial hand analysers such as ACCU-CHECK (Roche Diagnostics, Inc.), iSTAT (Abbot, Inc.), or Lactate Scout (Sports Resource Group, Inc.), for detecting metabolites and electrolytes. The present work demonstrates the fabrication and characterization of a wearable sensor which can help in real-time, non-invasive monitoring of metal ion levels (K + , Zn 2+ ) in perspiration directly from human epidermis. Potassium, one of the major constituents in sweat after sodium is important for the normal functioning of the human body in regulating blood pressure, normal water balance, muscle contractions and maintain pH balance of the body. It is also an important electrolyte present in the human body. Deficiency in potassium can lead to high blood pressure, muscle paralysis, breathing problems, irregular heart rhythms and constipation. Zinc, another metal present in trace levels in human perspiration; is a primary biomarker for muscular stress and fatigue. It is an important trace metal ion as it is involved in functioning of biochemical processes relevant to enzymes, hormones, and transcription related factors. Perspiration represents an efficient pathway for the release of potassium and zinc which leads to its deficiency in the body. Thus, monitoring of these metal ions in the body from perspiration becomes essential for athletes and for persons engaged in strenuous physical activity for the detection of wide ranging physiological states. Changes of potassium concentration in perspiration beyond optimal concentration (0.2 g/l) and zinc (1.56 µg/ml) can be used as indicators for physiological state of human body, such as low blood pressure and muscular stress and fatigue. While identifying the loss of these metal ions during physical activity is very important, currently very few tools exist for real-time detection of metal ion levels in perspiration. Electrochemical techniques such as stripping voltammetry have also been employed extensively for qualitative and quantitative detection of metal ions from the body. In-situ measurements have been demonstrated using micro-fabricated three-electrode assemblies utilizing expensive and laborious lithographic techniques. Although miniaturized and portable, such systems are not reusable and therefore are expensive and not scalable. Besides, their integration for real-time monitoring has been a challenge. Thus, the need of the hour is a detection system that combines ease of handling, real-time, in-situ analysis and specific detection of these metal ions in perspiration without compromising on the sensitivity reusability and cost-effectiveness. In order to achieve this, we have utilized novel molecular nanomaterials as transducers onto which the ion-selective receptors were immobilized. Specifically, the detection assembly consisted of cellulose fibres that were conformally coated with single wall carbon nanotubes (SWNTs). This resulted in a synergistic relation with the cellulose matrix providing the porosity and SWNTs providing the high specific surface area and electrical conduction pathway for signal transduction resulting in the fabrication of CNT-thread. Achieving ultrahigh sensitivity over a wide concentration range of analyte has been a persistent, mutually exclusive challenge for real-time analytical detection and diagnostics. To this end, we demonstrate a miniaturized, coaxial, cable-type electrochemical sensor comprised of a carbon nanotube immobilized cellulose yarn (CNT-thread) to achieve ultrahigh sensitivity (&lt;1 ppm) across a wide dynamic range (0.1−500 ppm) for the rapid (∼60 s) detection of K + and Zn 2+ . The sensor comprises of two cables of CNT-thread, one coated with a polymeric, ion-receptor (tetrakis(p-aminophenyl) porphyrin for Zn 2+ ) and Valinomycin for K + acting as the working electrode and the other being a reference electrode of pristine CNT-thread. The sensor is extremely tolerant to interference (selectivity coefficient 10 −3 −10 −5 ) from a wide range of cations (Na + , Mg 2+ , Cd 2+ , Ca 2+ , Fe 2+ , and Cu 2+ ) and anions (Cl − , NO 3 − , PO 4 3− , and CH 3 COO − ) enabling real-time detection of K + and Zn 2+ . Importantly, excellent signal consistency (&lt;5% deviation) across multiple electrochemical techniques such as cyclic voltammetry, differential pulse voltammetry, and chronoamperometry is demonstrated. Minimal deviation (&lt;6%) between the analyte concentrations estimated from the sensor and those estimated from atomic-absorption techniques is observed. Finally, the lifetime and mechanical sturdiness of the sensing platform is illustrated through elaborate experiments involving bending and seamless interfacing with human skin for noninvasive point-of-care analysis. Thus, this portable electrochemical platform enables the real-time analysis of metal ions in human perspiration without compromising on its sensitivity, reusability and cost-effectiveness.

Personalized non-invasive continuous glucose monitoring via multiparameter-informed machine learning.

Continuous blood pressure monitoring is essential in the management of patients in critical conditions, as well as those under anesthesia. However, continuous blood pressure monitoring requires insertion of a catheter into the radial artery. Thus, continuous noninvasive arterial blood pressure monitoring would be ideal. We designed and built a continuous noninvasive arterial blood pressure monitoring device with a pressure sensor diaphragm using microelectromechanical system technology, a square with 4 mm sides that were 0.4 mm thick. Comparisons between a continuous noninvasive arterial blood pressure monitoring device and a sphygmomanometer were carried out on 92 volunteers, and comparisons between noninvasive and invasive blood pressure monitoring were performed on three patients perioperatively at Fukushima Medical University Hospital. In the comparisons of arterial blood pressure measurements between a sphygmomanometer and our device, the differences became gradually greater over time after starting continuous monitoring in conscious participants. In the comparisons of arterial blood pressure measurements between the invasive and noninvasive methods in unconscious subjects under general anesthesia, the results of noninvasive monitoring were consistent with those of invasive arterial blood pressure monitoring. Continuous noninvasive arterial monitoring with a pressure sensor diaphragm using microelectromechanical system technology is a possible alternative to conventional invasive arterial pressure monitoring by an arterial catheter.

This study assessed the ability of a continuous non-invasive blood pressure (BP) monitoring system to reduce intra-anesthetic hemodynamic fluctuation compared with intermittent BP cuff measurement. Forty patients undergoing total knee arthroplasty under general anesthesia were enrolled and randomly divided into two groups (Control and CS group). BP management was performed using the same protocol with BP measured by intermittent BP cuff in the Control and that by continuous non-invasive BP monitoring in the CS group. We assessed the accuracy and precision of the continuous non-invasive BP monitoring compared with BP cuff measurement using Bland-Altman, four-quadrant plot, and polar-plot analyses. Additionally, the occurrence of hypotension and hypertention during general anesthesia was compared between the two groups. The continuous non-invasive BP monitoring showed excellent accuracy of - 1.1 ± 8.1mmHg during surgery and an acceptable trending ability with a concordance rate of 95.1% according to the four-quadrant plot analysis and an angular concordance rate of 86.7% by polar-plot analysis. Hypotension was less common in the CS group during induction of anesthesia (p = 0.002) and surgery (p = 0.008). Hypertension occurred more frequently in the Control group during emergence from anesthesia (p = 0.037). The duration of hemodynamic stability (systolic BP 80-110% of baseline) intraoperatively was longer in the CS group than in the Control group (87.7 vs. 61.9%; p < 0.001). Accuracy and trending ability of the continuous non-invasive BP monitoring was clinically acceptable, and lead to hemodynamic stability and reduction of intra-anesthetic hypotension and hypertension intraoperatively.

Continuous noninvasive arterial pressure monitoring devices are available for bedside use, but the accuracy and precision of these devices have not been evaluated in a systematic review and meta-analysis. The authors performed a systematic review and meta-analysis of studies comparing continuous noninvasive arterial pressure monitoring with invasive arterial pressure monitoring. Random-effects pooled bias and SD of bias for systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure were calculated. Continuous noninvasive arterial pressure monitoring was considered acceptable if pooled estimates of bias and SD were not greater than 5 and 8 mmHg, respectively, as recommended by the Association for the Advancement of Medical Instrumentation. Twenty-eight studies (919 patients) were included. The overall random-effect pooled bias and SD were -1.6 ± 12.2 mmHg (95% limits of agreement -25.5 to 22.2 mmHg) for systolic arterial pressure, 5.3 ± 8.3 mmHg (-11.0 to 21.6 mmHg) for diastolic arterial pressure, and 3.2 ± 8.4 mmHg (-13.4 to 19.7 mmHg) for mean arterial pressure. In 14 studies focusing on currently commercially available devices, bias and SD were -1.8 ± 12.4 mmHg (-26.2 to 22.5 mmHg) for systolic arterial pressure, 6.0 ± 8.6 mmHg (-10.9 to 22.9 mmHg) for diastolic arterial pressure, and 3.9 ± 8.7 mmHg (-13.1 to 21.0 mmHg) for mean arterial pressure. The results from this meta-analysis found that inaccuracy and imprecision of continuous noninvasive arterial pressure monitoring devices are larger than what was defined as acceptable. This may have implications for clinical situations where continuous noninvasive arterial pressure is being used for patient care decisions.

There is a growing trend across health care to perform increasingly complex procedures in less acute settings. This shift has been fueled, in part, by enhanced recovery protocols, which have shortened hospital stays after major surgeries. We set out to determine the timing of microvascular complications after deep inferior epigastric artery perforator (DIEP) free flap breast reconstruction in a high-volume practice using continuous flap monitoring technologies. The medical charts of all patients who underwent breast reconstruction with DIEP flaps over 24 consecutive months were reviewed. Postoperatively, all flaps were monitored according to a protocol that included continuous tissue oximetry with near-infrared spectroscopy. The primary end points evaluated included any unplanned return to the operating room, time to takeback, and flap loss rate. A total of 196 patients underwent breast reconstruction with a total of 301 DIEP flaps. Five of the flaps (1.7%) were taken back to the operating room for microvascular issues, and nine (3.0%) were taken back for nonvascular issues. Of patients who were brought back for microvascular issues, all five (100.0%) were initially identified by continuous noninvasive monitoring and taken back to the operating room within the first 14 hours (range: 1.2-13.6 hours). In the series, the flap failure rate was 0.66% (n = 2). All of the microvascular issues were detected in the initial 23 hours after surgery, leading to prompt flap salvage. The results of this study bring into question the need for lengthy flap monitoring protocols and suggest that shorter inpatient, or even observation admissions, may be reasonable, particularly when flap monitoring protocols incorporating continuous noninvasive flap monitoring are used.

IntroductionHaemorrhagic transformation (HT) seriously worsens functional outcome after endovascular therapy (EVT). Blood pressure (BP) variability may influence HT risk, but optimal monitoring strategies remain unclear. We aimed to determine whether continuous BP monitoring better identifies patients at risk of HT than standard intermittent measurements during the first 24 h post-EVT.Patients and methodsWe conducted a single-centre prospective cohort study including adults with acute ischaemic stroke due to large-vessel occlusion treated with EVT. Non-invasive finger-cuff continuous BP and arm-cuff intermittent BP were recorded simultaneously for 24 h post-EVT. Haemorrhagic transformation on follow-up brain imaging at 24–36 h was the primary outcome. Blood pressure recordings were partitioned into three 8-h windows. Variability metrics (mean, maximum, range, SD, coefficient of variation and wavelet-based coefficient energies) were processed into logistic regression models adjusted for clinical covariates. Predictive performance was assessed using AUC-ROC.ResultsAmong 455 enrolled patients, 199 contributed data to the first 8-h window, in which HT occurred in 58 (29%). Continuous BP variability features, particularly maximum, range and wavelet energies capturing < 32-min fluctuations, were significantly associated with HT, whereas no parameter from intermittent monitoring showed such an association. A multivariable model using continuous data yielded an AUC-ROC of 0.62 (95% CI, 0.54–0.71) vs 0.48 (95% CI, 0.37–0.58) for intermittent data. Associations were not observed in later windows.Discussion and conclusionShort-timescale BP variability captured by continuous monitoring in the first 8 h post-EVT is associated with increased HT risk, whereas intermittent monitoring fails to detect this signal and may miss opportunities for early risk stratification.

Early detection of hypertension generally requires continuous monitoring of blood pressure levels which is not facilitated by traditional methods such as the cuff, which cannot be used in the normal environment for continuous monitoring due to the regular pressurization of certain body parts. Thus there is a need for non-invasive continuous pressure monitoring mechanism. In this paper we present a relationship between Pulse Transit Time (PTT) and Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for continuous pressure monitoring and its experimental validation.