Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.

Wearable biosensors for healthcare monitoring.

Recent developments in paper-based microfluidic devices.

Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate.

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat

Rapid progress in identifying biomarkers that are hallmarks of disease has increased demand for high-performance detection technologies. Implementation of electrochemical methods in clinical analysis may provide an effective answer to the growing need for rapid, specific, inexpensive, and fully automated means of biomarker analysis. This Review summarizes advances from the past 5 years in the development of electrochemical sensors for clinically relevant biomolecules, including small molecules, nucleic acids, and proteins. Various sensing strategies are assessed according to their potential for reaching relevant limits of sensitivity, specificity, and degrees of multiplexing. Furthermore, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms into point-of-care solutions.

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Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules

Recent advances in soft materials and system integration technologies have provided a unique opportunity to design various types of wearable flexible hybrid electronics (WFHE) for advanced human healthcare and human-machine interfaces. The hybrid integration of soft and biocompatible materials with miniaturized wireless wearable systems is undoubtedly an attractive prospect in the sense that the successful device performance requires high degrees of mechanical flexibility, sensing capability, and user-friendly simplicity. Here, the most up-to-date materials, sensors, and system-packaging technologies to develop advanced WFHE are provided. Details of mechanical, electrical, physicochemical, and biocompatible properties are discussed with integrated sensor applications in healthcare, energy, and environment. In addition, limitations of the current materials are discussed, as well as key challenges and the future direction of WFHE. Collectively, an all-inclusive review of the newly developed WFHE along with a summary of imperative requirements of material properties, sensor capabilities, electronics performance, and skin integrations is provided.

Advanced Soft Materials, Sensor Integrations, and Applications of Wearable Flexible Hybrid Electronics in Healthcare, Energy, and Environment.

The mobile health market is rapidly expanding and portable diagnostics tools offer an opportunity to decrease costs and increase the availability of healthcare. Here we present a smartphone based accessory and method for the rapid colorimetric detection of pH in sweat and saliva. Sweat pH can be correlated to sodium concentration and sweat rate in order to indicate to users the proper time to hydrate during physical exercise and avoid the risk of muscle cramps. Salivary pH below a critical threshold is correlated with enamel decalcification, an acidic breakdown of calcium in the teeth. We conduct a number of human trials with the device on a treadmill to demonstrate the ability to monitor changes in sweat pH due to exercise and electrolyte intake and predict optimal hydration. Additionally, we perform trials to measure salivary pH over time to monitor the effects of diet on oral health risks.

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Smartphone based health accessory for colorimetric detection of biomarkers in sweat and saliva

Home self-diagnostic tools for blood cholesterol monitoring have been around for over a decade but their widespread adoption has been limited by the relatively high cost of acquiring a quantitative test-strip reader, complicated procedure for operating the device, and inability to easily store and process results. To address this we have developed a smartphone accessory and software application that allows for the quantification of cholesterol levels in blood. Through a series of human trials we demonstrate that the system can accurately quantify total cholesterol levels in blood within 60 s by imaging standard test strips. In addition, we demonstrate how our accessory is optimized to improve measurement sensitivity and reproducibility across different individual smartphones. With the widespread adoption of smartphones and increasingly sophisticated image processing technology, accessories such as the one presented here will allow cholesterol monitoring to become more accurate and widespread, greatly improving preventive care for cardiovascular disease.

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Cholesterol testing on a smartphone

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260 M active smartphones in the US and millions of health accessories and software “apps” running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings.

/pdf/smartphone-technology-can-be-transformative-to-the-1pnitu8c71.pdf

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics

Vitamin D deficiency has been linked to a number of diseases and adverse outcomes including: osteoporosis, infections, diabetes, cardiovascular diseases, and even cancer. At present the vast majority of vitamin D testing is performed in large-scale laboratories at the request of a physician as part of an annual panel of blood tests. Here we present a system for rapid quantification of vitamin D levels on a smartphone. The system consists of a smartphone accessory, an app, and a test strip that allows the colorimetric detection of 25-hydroxyvitamin D using a novel gold nanoparticle-based immunoassay. We show that the system can be used to accurately measure physiological levels of 25-hydroxyvitamin D with accuracy better than 15 nM and a precision of 10 nM. We compare our system with well-established ELISA test kits for serum samples of unknown concentration and demonstrate equivalency of the results. We envision this as the first step towards the development of the NutriPhone, a comprehensive system for the analysis of multiple vitamins and micronutrients on a smartphone.

https://nano.mae.cornell.edu/pubs/Lee_LOAC_2014.pdf

A smartphone platform for the quantification of vitamin D levels.

A method for obtaining a point-of-collection, selected quantitative indicia of an analyte on a test strip using a smartphone involves imaging a test strip on which a colorimetric reaction of a target sample has occurred due to test strip illumination by the smartphone. The smartphone includes a smartphone app and a smartphone accessory that provides an external environment-independent/internal light-free, imaging environment independent of the smartphone platform being used. The result can then be presented quantitatively or turned into a more consumer-friendly measurement (positive, negative, above average, etc.), displayed to the user, stored for later use, and communicated to a location where practitioners can provide additional review. Additionally, social media integration can allow for device results to be broadcast to specific audiences, to compare healthy living with others, to compete in health based games, create mappings, and other applications.

Vlad Oncescu

Papers

Smartphone based health accessory for colorimetric detection of biomarkers in sweat and saliva

Cholesterol testing on a smartphone

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics

A smartphone platform for the quantification of vitamin D levels.

Smartphone-based apparatus and method for obtaining repeatable, quantitative colorimetric measurement