Applied body-fluid analysis by wearable devices

Abstract

Wearable sensors are a recent paradigm in healthcare, enabling continuous, decentralized, and non- or minimally invasive monitoring of health and disease. Continuous measurements yield information-rich time series of physiological data that are holistic and clinically meaningful. Although most wearable sensors were initially restricted to biophysical measurements, the next generation of wearable devices is now emerging that enable biochemical monitoring of both small and large molecules in a variety of body fluids, such as sweat, breath, saliva, tears and interstitial fluid. Rapidly evolving data analysis and decision-making technologies through artificial intelligence has accelerated the application of wearables around the world. Although recent pilot trials have demonstrated the clinical applicability of these wearable devices, their widespread adoption will require large-scale validation across various conditions, ethical consideration and sociocultural acceptance. Successful translation of wearable devices from laboratory prototypes into clinical tools will further require a comprehensive transitional environment involving all stakeholders. The wearable device platforms must gain acceptance among different user groups, add clinical value for various medical indications, be eligible for reimbursements and contribute to public health initiatives. In this Perspective, we review state-of-the-art wearable devices for body-fluid analysis and their translation into clinical applications, and provide insight into their clinical purpose.

Fig. 1 ∣. The anatomy of wearable sensing platforms for body-fluid analysis.

a, For sweat sensing, an electronic skin is shown that enables multimodal sensing including biochemical sweat analysis (such as Na⁺, NH₄⁺, K⁺, lactate, glucose and uric acid) combined with biophysical measures (such as temperature, pulse and galvanic skin response (GSR)). Scale bar, 1 cm. CARES, consolidated artificial-intelligence-reinforced electronic skin; PDMS, polydimethylsiloxane. b, For ISF sensing, a microneedle-based device with a disposable sensor and reusable electronics is shown that allows monitoring of glucose, lactate and alcohol. A microneedle sensor patch with a disposable sensor array and reusable electronics visualized from the front (i). Scale bar, 1.5 cm. Sensing results are displayed on the smartphone of the user (ii). The tip of an individual microneedle electrode visualized by scanning electron microscopy (iii). Scale bar, 75 μm. MNeedle array, microneedle array; PCB, printed circuit board. c, For breath sensing, a CRISPR-based lateral flow assay (LFA) platform along with an origami sample preparation unit is shown that is embedded into a facemask, enabling straightforward detection of SARS-CoV-2 genes. RT-RPA, reverse transcription-recombinase polymerase amplification; SHERLOCK, a CRISPR-based molecular diagnostic tool; μPAD, microfluidic paper-based analytical device. Panels reproduced with permission from: a, ref. , Springer Nature Ltd; b, ref. , Springer Nature Ltd; c, ref. , Springer Nature Ltd.

Fig. 2 ∣. Current wearable sensing devices for various body fluids in context of the human life cycle.

Each life cycle comes with differing challenges and needs. It is crucial to understand the relation between age and disease as well as to integrate these with the usability. Thus wearable sensors might be developed as pacifiers for toddlers, rings for adults and hearing aids for people of advanced age. ECG, electrocardiogram.

Fig. 3 ∣. The development of digital endpoints.

The development of digital endpoints begins with understanding the context of use and defining the concept of interest, including the measurements and the digital technology. Only after thorough validation, a digital endpoint is ready to serve in clinical trials. Workflow based on recommendations of the CTTI (ctti-clinicaltrials.org).

Fig. 4 ∣. Applied body-fluid analysis by wearable devices in clinical medicine.

Schematic overviews are provided of how wearable devices can improve the current standard of care in molecular body-fluid analysis by facilitating access to continuous and lab-independent monitoring and adding information from various body fluids collected in different locations. a, One example application is for monitoring antibiotic treatments to manage bacterial infections. So far, assessing bacterial infections to identify the underlining pathogen, assess the state of inflammation and monitor drug concentrations have been mainly feasible in specialized laboratories using time-consuming and costly procedures. The integration of these tests into connectable, smartphone-based analytics enables a seamless and patient-centred health monitoring at the hospital and in the outpatient setting. GP, general practitioner; IL-6, interleukin-6; IL-10, interleukin-10; TNF, tumour necrosis factor. b, Another example application is for facilitating healthcare access to complex diagnostics in resource-scarce areas of the world. Body-fluid analysis by wearable devices can allow to identify and monitor lower respiratory infections, diseases leading to exanthema, eye diseases, and metabolic disorders at sea and on land by choosing the respective biosensor and body fluid by medical indication. SpO₂, peripheral arterial oxygen saturation.