Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

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Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

Emerging pollutants in the environment: present and future challenges in biomonitoring, ecological risks and bioremediation

Sweat potentially contains a wealth of physiologically relevant information, but has traditionally been an underutilized resource for non-invasive health monitoring. Recent advances in wearable sweat sensors have overcome many of the historic drawbacks of sweat sensing and such sensors now offer methods of gleaning molecular-level insight into the dynamics of our bodies. Here we review key developments in sweat sensing technology. We highlight the potential value of sweat-based wearable sensors, examine state-of-the-art devices and the requirements of the underlying components, and consider ways to tackle data integrity issues within these systems. We also discuss challenges and opportunities for wearable sweat sensors in the development of personalized healthcare.

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Wearable sweat sensors

The early detection of cancer can significantly reduce cancer mortality and saves lives. Thus, a great deal of effort has been devoted to the exploration of new technologies to detect early signs of the disease. Cancer biomarkers cover a broad range of biochemical entities, such as nucleic acids, proteins, sugars, small metabolites, and cytogenetic and cytokinetic parameters, as well as entire tumour cells found in the body fluid. They can be used for risk assessment, diagnosis, prognosis, and for the prediction of treatment efficacy and toxicity and recurrence. In this review, we provide an overview of recent advances in cancer biomarker detection. Several representative examples using different approaches for each biomarker have been reviewed, and all these cases demonstrate that the multidisciplinary technology-based cancer diagnostics are becoming an increasingly relevant alternative to traditional techniques. In addition, we also discuss the unsolved problems and future challenges in the evaluation of cancer biomarkers. Clearly, solving these hurdles requires great effort and collaboration from different communities of chemists, physicists, biologists, clinicians, material-scientists, and engineering and technical researchers. A successful outcome will result in the realization of point-of-care diagnosis and individualized treatment of cancers by non-invasive and convenient tests in the future.

Cancer biomarker detection: recent achievements and challenges

Titanium Dioxide Nanomaterials for Sensor Applications

Quantification of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. However, converting the biological information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biological environment. Electrochemical biosensors provide an attractive means to analyze the content of a biological sample due to the direct conversion of a biological event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Additional measurement techniques, which have been shown useful in combination with electrochemical detection, are also summarized, such as the electrochemical versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochemical sensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.

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Electrochemical Biosensors - Sensor Principles and Architectures

Large area arrays of metal nanowires

This work explores the alternative use of noble metal nanowire systems in large-scale array configurations to exploit both the nanowires’ conductive nature and localized surface plasmon resonance (LSPR). The first known nanowire-based system has been constructed, with which optical signals are influenced by the simultaneous application of electrochemical potentials. Optical characterization of nanowire arrays was performed by measuring the bulk refractive index sensitivity and the limit of detection. The formation of an electrical double layer was controlled in NaCl solutions to study the effect of local refractive index changes on the spectral response. Resonance peak shifts of over 4 nm, a bulk refractive index sensitivity up to 115 nm/RIU and a limit of detection as low as 4.5 × 10−4 RIU were obtained for gold nanowire arrays. Simulations with the Multiple Multipole Program (MMP) confirm such bulk refractive index sensitivities. Initial experiments demonstrated successful optical biosensing using a novel form of particle-based nanowire arrays. In addition, the formation of an ionic layer (Stern-layer) upon applying an electrochemical potential was also monitored by the shift of the plasmon resonance.

https://www.mdpi.com/1424-8220/10/11/9808/pdf

Optical sensing with simultaneous electrochemical control in metal nanowire arrays.

Simultaneous LSPR and electronic sensing of potential induced ion adsorption onto gold nanowire arrays is presented. The formation of a Stern layer upon applying an electrochemical potential generated a complex optical response. Simulation of a lossy atomic layer on the nanowire array using the Multiple Multipole Program (MMP) corresponded very well to the experimentally observed peak position, intensity, and radius of curvature changes. Additionally, a significant voltage-dependent change in the resistance of the gold nanowire array was observed during the controlled formation of the electrical double layer. The results demonstrated that an applied electrochemical potential induces measurable changes in the optical and electrical properties of the gold nanowire surface. This is the first demonstration of combined plasmonic and nanowire resistance-based sensing of a surface process in the literature.

Simultaneous electrical and plasmonic monitoring of potential induced ion adsorption on metal nanowire arrays.

A nanowire is an extremely thin wire with a diameter on the order of a few nanometers and with lengths orders of magnitude larger than its diameter. The physical properties of nanowires at this scale are expected to deviate significantly from the bulk metal, due to confinement and surface effects. For example, the electrical conductivity of the wires changes considerably, due to the drastic increase in the surface-to-volume ratio, which can be exploited for sensing. Mechanical properties, such as the yield strength, are important parameters that need to be characterized for applications like flexible circuits. In order to study the nanowire properties one needs to arrange them on a surface in a controlled way.

Robert MacKenzie

Papers

Electrochemical Biosensors - Sensor Principles and Architectures

Large area arrays of metal nanowires

Optical sensing with simultaneous electrochemical control in metal nanowire arrays.

Simultaneous electrical and plasmonic monitoring of potential induced ion adsorption on metal nanowire arrays.

Nanowire Development and Characterization for Applications in Biosensing