Self-powered freestanding multifunctional microneedle-based extended gate device for personalized health monitoring.

Online monitoring of prognostic biomarkers is critically important when diagnosing disorders and assessing individuals' health, especially for chronic and infectious diseases. Despite this, current diagnosis techniques are time-consuming, labor-intensive, and performed offline. In this context, developing wearable devices for continuous measurements of multiple biomarkers from body fluids has considerable advantages including availability, rapidity, convenience, and minimal invasiveness over the conventional painful and time-consuming tools. However, there is still a significant challenge in powering these devices over an extended period, especially for applications that require continuous and long-term health monitoring. Herein, a new freestanding, wearable, multifunctional microneedle-based extended gate field effect transistor biosensor is fabricated for online detection of multiple biomarkers from the interstitial fluid including sodium, calcium, potassium, and pH along with excellent electrical response, reversibility, and precision. In addition, a hybrid powering system of triboelectric nanogenerator and solar cell was developed for creating a freestanding, closed-loop platform for continuous charging of the device's battery and integrated with an Internet of Things technology to broadcast the measurements online, suggesting a stand-alone, stable multifunctional tool which paves the way for advanced practical personalized health monitoring and diagnosis.

The diagnostic breathprint of cancer; the past and the future.

The main milestones in the exploration and validation of cancer breathprint for the advancement of personalised diagnosis and medicine are summarised here, with a special attention to the appraisal and translation of the accumulating knowledge from the laboratory to the Point-of-Care phase. An outlook into the opportunities of the use of breathprints and their wider availability for healthcare is offered.

Wearable Clinic: From Microneedle-Based Sensors to Next-Generation Healthcare Platforms.

The rapid development of wearable biosensing calls for next-generation devices that allow continuous, real-time, and painless monitoring of health status along with responsive medical treatment. Microneedles have exhibited great potential for the direct access of dermal interstitial fluid (ISF) in a minimally invasive manner. Recent studies of microneedle-based devices have evolved from conventional off-line detection to multiplexed, wireless, and integrated sensing. In this review, the classification and fabrication techniques of microneedles are first introduced, and then the representative examples of microneedles for transdermal monitoring with different sensing modalities are summarized. State-of-the-art advances in therapeutic and closed-loop systems are presented to formulate guidelines for the development of next-generation microneedle-based healthcare platforms. The potential challenges and prospects are discussed to pave a new avenue toward pragmatic applications in the real world.

Skin bioelectronics towards long-term, continuous health monitoring.

Skin bioelectronics are considered as an ideal platform for personalised healthcare because of their unique characteristics, such as thinness, light weight, good biocompatibility, excellent mechanical robustness, and great skin conformability. Recent advances in skin-interfaced bioelectronics have promoted various applications in healthcare and precision medicine. Particularly, skin bioelectronics for long-term, continuous health monitoring offer powerful analysis of a broad spectrum of health statuses, providing a route to early disease diagnosis and treatment. In this review, we discuss (1) representative healthcare sensing devices, (2) material and structure selection, device properties, and wireless technologies of skin bioelectronics towards long-term, continuous health monitoring, (3) healthcare applications: acquisition and analysis of electrophysiological, biophysical, and biochemical signals, and comprehensive monitoring, and (4) rational guidelines for the design of future skin bioelectronics for long-term, continuous health monitoring. Long-term, continuous health monitoring of advanced skin bioelectronics will open unprecedented opportunities for timely disease prevention, screening, diagnosis, and treatment, demonstrating great promise to revolutionise traditional medical practices.

Gate-Controlled Chiral Recognition and Spin Assessment with All-Electric Hybrid Quantum Wire-Based Transistors.

The search for inexpensive and all-electric tunable methods for portable and fast recognition and discrimination between various chiral enantiomers, mainly those found in the gas phase, has been one of the most challenging tasks in the field of analytical chemistry. The current article reports on a chiral sensitive electric architecture (CSEA) of a helical polyaniline (PANI)@carbon nanotube (CNT) hybrid quantum-wire based field effect transistor (FET) platform. The CSEA architecture exhibits gate-controlled-channel-chirality modulation for the selective distinction of Limonene (S(+)/R(-)) at ≈12 V intervals. Typical gate-modulated selectivity of S(+)-Limonene and R(-)-Limonene using two opposite helically turned hybrids, namely as, S-PANI@CNT and R-PANI@CNT are 6.5 and 2.8, respectively. Theoretical analysis and modelling relates the gas-phase chiral quantum probe with spin-channel modulation in CNT by Rashba spin-orbit interaction. This is achieved by applied gate voltage, CNT's unique curved surface, adsorbed chiral adatom induced scattering center on the curved graphitic lattice and helicoid field from a synthetically prepared helical PANI@CNT hybrid interface.

Detecting Coronary Artery Disease Using Exhaled Breath Analysis.

INTRODUCTION: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide, and there is an unmet need for a simple, inexpensive, noninvasive tool aimed at CAD detection. The aim of this pilot study was to evaluate the possible use of breath analysis in detecting the presence of CAD. MATERIALS AND METHODS: In a prospective study, breath from patients with no history of CAD who presented with acute chest pain to the emergency room was sampled using a designated portable electronic nose (eNose) system. First, breath samples from 60 patients were analyzed and categorized as obstructive, nonobstructive, and no-CAD according to the actual presence and extent of CAD as was demonstrated on cardiac imaging (either computerized tomography angiography or coronary angiography). Classification models were built according to the results, and their diagnostic performance was then examined in a blinded manner on a new set of 25 patients. The data were compared with the actual results of coronary arteries evaluation. Sensitivity, specificity, and accuracy were calculated for each model. RESULTS: Obstructive CAD was correctly distinguished from nonobstructive and no-CAD with 89% sensitivity, 31% specificity, 83% negative predictive value (NPV), 42% positive predictive value (PPV), and 52% accuracy. In another model, any extent of CAD was successfully distinguished from no-CAD with 69% sensitivity, 67% specificity, 54% NPV, 79% PPV, and 68% accuracy. CONCLUSION: This proof-of-concept study shows that breath analysis has the potential to be used as a novel rapid, noninvasive diagnostic tool to help identify presence of CAD in patients with acute chest pain.

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines.

In vitro studies can help reveal the biochemical pathways underlying the origin of volatile indicators of numerous diseases. The key objective of this study is to identify the potential biomarkers of gastric cancer. For this purpose, the volatilomic signatures of two human gastric cancer cell lines, AGS (human gastric adenocarcinoma) and SNU-1 (human gastric carcinoma), and one normal gastric mucosa cell line (GES-1) were investigated. More specifically, gas chromatography mass spectrometry has been applied to pinpoint changes in cell metabolism triggered by cancer. In total, ten volatiles were found to be metabolized, and thirty-five were produced by cells under study. The volatiles consumed were mainly six aldehydes and two heterocyclics, whereas the volatiles released embraced twelve ketones, eight alcohols, six hydrocarbons, three esters, three ethers, and three aromatic compounds. The SNU-1 cell line was found to have significantly altered metabolism in comparison to normal GES-1 cells. This was manifested by the decreased production of alcohols and ketones and the upregulated emission of esters. The AGS cells exhibited the increased production of methyl ketones containing an odd number of carbons, namely 2-tridecanone, 2-pentadecanone, and 2-heptadecanone. This study provides evidence that the cancer state modifies the volatilome of human cells.

Sensing gastric cancer via point-of-care sensor breath analyzer.

BACKGROUND: Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT-connected point-of-care device (so-called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening. METHODS: A validation study of patients with gastric cancer, patients with high-risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant analysis (LDA) was used as a classifying model of the sensing signals obatined from the examined groups. For the testing step, an additional device was added. The study group included 274 patients: 94 with gastric cancer, 67 who were in the high-risk group, and 113 controls. RESULTS: The results of the test set showed a clear discrimination between patients with gastric cancer and controls using the 2-device LDA model (area under the curve, 93.8%; sensitivity, 100%; specificity, 87.5%; overall accuracy, 91.1%), and acceptable results were also achieved for patients with high-risk lesions (the corresponding values for dysplasia were 84.9%, 45.2%, 87.5%, and 65.9%, respectively). The test-phase analysis showed lower accuracies, though still clinically useful. CONCLUSION: Our results demonstrate that a portable breath sensor device could be useful in point-of-care settings. It shows a promise for detection of gastric cancer as well as for other types of disease. LAY SUMMARY: A portable sensor-based breath analyzer for detection of gastric cancer can be used in point-of-care settings. The results are transferrable between devices via advanced IoT technology. Both the hardware and software of the reported breath analyzer could be easily modified to enable detection and monitirng of other disease states.

Disease Detection with Molecular Biomarkers: From Chemistry of Body Fluids to Nature-Inspired Chemical Sensors.

This article aims to review nature-inspired chemical sensors for enabling fast, relatively inexpensive, and minimally (or non-) invasive diagnostics and follow-up of the health conditions. It can be achieved via monitoring of biomarkers and volatile biomarkers, that are excreted from one or combination of body fluids (breath, sweat, saliva, urine, seminal fluid, nipple aspirate fluid, tears, stool, blood, interstitial fluid, and cerebrospinal fluid). The first part of the review gives an updated compilation of the biomarkers linked with specific sickness and/or sampling origin. The other part of the review provides a didactic examination of the concepts and approaches related to the emerging chemistries, sensing materials, and transduction techniques used for biomarker-based medical evaluations. The strengths and pitfalls of each approach are discussed and criticized. Future perspective with relation to the information and communication era is presented and discussed.

A Highly Aligned Nanowire-Based Strain Sensor for Ultrasensitive Monitoring of Subtle Human Motion.

Achieving highly accurate responses to external stimuli during human motion is a considerable challenge for wearable devices. The present study leverages the intrinsically high surface-to-volume ratio as well as the mechanical robustness of nanostructures for obtaining highly-sensitive detection of motion. To do so, highly-aligned nanowires covering a large area were prepared by capillarity-based mechanism. The nanowires exhibit a strain sensor with excellent gauge factor (≈35.8), capable of high responses to various subtle external stimuli (≤200 µm deformation). The wearable strain sensor exhibits also a rapid response rate (≈230 ms), mechanical stability (1000 cycles) and reproducibility, low hysteresis (<8.1%), and low power consumption (<35 µW). Moreover, it achieves a gauge factor almost five times that of microwire-based sensors. The nanowire-based strain sensor can be used to monitor and discriminate subtle movements of fingers, wrist, and throat swallowing accurately, enabling such movements to be integrated further into a miniaturized analyzer to create a wearable motion monitoring system for mobile healthcare.

A Freestanding Stretchable and Multifunctional Transistor with Intrinsic Self-Healing Properties of all Device Components.

A flexible and stretchable field-effect transistor (FET) is an essential element in a number of modern electronics. To realize the potential of this device in harsh real-world conditions and to extend its application spectrum, new functionalities are needed to be introduced into the device. Here, solution-processable elements based on carbon nanotubes that empower flexible and stretchable FET with high hole-mobility (µh ≈ 10 cm2 V-1 s-1 ) and relatively low operating voltages (<8 V) and that retain self-healing properties of all FET components are reported. The device has repeatable intrinsic and autonomic self-healing ability, namely without use of any external trigger, enabling the restoration of its electrical and mechanical properties, both after microscale damage or complete cut of the device-for example by a scissor. The device can be repeatedly stretched for >200 cycles of up to 50% strain without a significant loss in its electrical properties. The device is applicable in the form of a ≈3 µm thick freestanding skin tattoo and has multifunctional sensing properties, such as detection of temperature and humidity. With this unprecedented biomimetic transistor, highly sustainable and reliable soft electronic applications can be introduced.

Synergy between nanomaterials and volatile organic compounds for non-invasive medical evaluation.

This article is an overview of the present and ongoing developments in the field of nanomaterial-based sensors for enabling fast, relatively inexpensive and minimally (or non-) invasive diagnostics of health conditions with follow-up by detecting volatile organic compounds (VOCs) excreted from one or combination of human body fluids and tissues (e.g., blood, urine, breath, skin). Part of the review provides a didactic examination of the concepts and approaches related to emerging sensing materials and transduction techniques linked with the VOC-based non-invasive medical evaluations. We also present and discuss diverse characteristics of these innovative sensors, such as their mode of operation, sensitivity, selectivity and response time, as well as the major approaches proposed for enhancing their ability as hybrid sensors to afford multidimensional sensing and information-based sensing. The other parts of the review give an updated compilation of the past and currently available VOC-based sensors for disease diagnostics. This compilation summarizes all VOCs identified in relation to sickness and sampling origin that links these data with advanced nanomaterial-based sensing technologies. Both strength and pitfalls are discussed and criticized, particularly from the perspective of the information and communication era. Further ideas regarding improvement of sensors, sensor arrays, sensing devices and the proposed workflow are also included.

Volatolomics of breath as an emerging frontier in pulmonary arterial hypertension.

There is accumulating evidence in support of the significant improvement in survival rates and clinical outcomes when pulmonary arterial hypertension (PAH) is diagnosed at early stages. Nevertheless, it remains a major clinical challenge and the outcomes are dependent on invasive right heart catheterisation.Resulting from pathophysiological processes and detectable in exhaled breath, volatile organic compounds (VOCs) have been proposed as noninvasive biomarkers for PAH. Studies have confirmed significant alterations of the exhaled VOCs among PAH patients when compared to controls and/or patients with other respiratory diseases. This suggests exhaled breath analysis as a potential noninvasive medical application in the field of PAH.In this article, we review and discuss the progress made so far in the field of exhaled volatolomics (the omics of VOCs) as a potential noninvasive diagnostics of PAH. In addition, we propose a model including possible biochemical pathways on the level of the remodelled artery, in which specific VOCs could be detectable in exhaled breath during the early phases of PAH. We debate the different analytical approaches used and recommend a diagram including a "bottom-top" strategy, from basic to translational studies, required for promoting the field.

Self-Healable Sensors Based Nanoparticles for Detecting Physiological Markers via Skin and Breath: Toward Disease Prevention via Wearable Devices.

Flexible and wearable electronic sensors are useful for the early diagnosis and monitoring of an individual's health state. Sampling of volatile organic compounds (VOCs) derived from human breath/skin or monitoring abrupt changes in heart-beat/breath rate should allow noninvasive monitoring of disease states at an early stage. Nevertheless, for many reported wearable sensing devices, interaction with the human body leads incidentally to unavoidable scratches and/or mechanical cuts and bring about malfunction of these devices. We now offer proof-of-concept of nanoparticle-based flexible sensor arrays with fascinating self-healing abilities. By integrating a self-healable polymer substrate with 5 kinds of functionalized gold nanoparticle films, a sensor array gives a fast self-healing (<3 h) and attractive healing efficiency in both the substrate and sensing films. The proposed platform was used in sensing pressure variation and 11 kinds of VOCs. The sensor array had satisfactory sensitivity, a low detection limit, and promising discrimination features in monitoring both of VOCs and pressure variation, even after full healing. These results presage a new type of smart sensing device, with a desirable performance in the possible detection and/or clinical application for a number of different purposes.

Detection of precancerous gastric lesions and gastric cancer through exhaled breath.

OBJECTIVES: Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence. DESIGN: 968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value<0.017); the second by cross-reactive nanoarrays combined with pattern recognition. For the latter, 70% of the samples were randomly selected and used in the training set while the remaining 30% constituted the validation set. The operative link on gastric intestinal metaplasia (OLGIM) assessment staging system was used to stratify the presence/absence and risk level of precancerous lesions. Patients with OLGIM stages III-IV were considered to be at high risk. RESULTS: According to the GCMS results, patients with cancer as well as those at high risk had distinctive breath-print compositions. Eight significant volatile organic compounds (p value<0.017) were detected in exhaled breath in the different comparisons. The nanoarray analysis made it possible to discriminate between the patients with GC and the control group (OLGIM 0-IV) with 73% sensitivity, 98% specificity and 92% accuracy. The classification sensitivity, specificity, and accuracy between the subgroups was as follows: GC versus OLGIM 0-II-97%, 84% and 87%; GC versus OLGIM III-IV-93%, 80% and 90%; but OLGIM I-II versus OLGIM III-IV and dysplasia combined-83%, 60% and 61%, respectively. CONCLUSIONS: Nanoarray analysis could provide the missing non-invasive screening tool for GC and related precancerous lesions as well as for surveillance of the latter. TRIAL REGISTRATION NUMBER: Clinical Trials.gov number, NCT01420588 (3/11/2013).

Breath testing as potential colorectal cancer screening tool.

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC-MS) for identification and quantification of volatile organic compounds (VOCs). The T-test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave-one-out cross validation was conducted for validation. The GC-MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4-methyl octane (lower in CRC). The sensor-analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non-advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.

Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath.

Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases.

Ultrasensitive silicon nanowire for real-world gas sensing: noninvasive diagnosis of cancer from breath volatolome.

We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.

Assessment of ovarian cancer conditions from exhaled breath.

We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor-free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.