Sweat as a Reservoir of Non-Invasive Biomarkers for Clinical Diagnosis

Despite its frequent association with stressful or uncomfortable situations, sweat is a body fluid that contains disease-specific markers and drug metabolites, making it a potential source of biomarkers for clinical diagnosis. The field of sweat research has recently experienced a surge of interest, mainly due to its noninvasive, convenient, and easily collected nature, which makes it more attractive than other body fluids such as blood, urine, saliva, and cerebrospinal fluid.

In addition, the advent of wearable sensors, often in the form of wireless smartphone-linked devices, has made sweat analysis more accessible and convenient, leading to its wider application in healthcare.  As a result, traditional analysis of clinical samples will increasingly be complemented and in some cases replaced by sweat analysis.

In 1910, Embden et al. discovered the presence of serine in human sweat (1), thereby confirming for the first time the existence of protein components in sweat, thus stimulating further research into its composition. This research led to identifying other significant biomarkers in the following years, including glucose, ammonia, chloride, fatty acids and prostaglandins (2-5), thereby expanding the range of biomarkers that could be analysed in sweat.

Concurrently, numerous research efforts were undertaken to explore the correlation between sweat composition and disease. In particular, a study performed by Prompt and colleagues in 1978 on patients with renal failure revealed increased magnesium, calcium, and phosphate levels in sweat, indicating disease-specific ion changes (6). These findings provide a compelling basis for considering sweat as a potential source of biomarkers useful for diagnostic purposes.

Sweat is a Complex Fluid with Clues to Health and Disease

Sweat is typically a clear biological fluid that is mainly composed of water (about 99%)(7) and slightly acidic (with an average pH of 6.3). It contains small amounts of metallic and non-metallic ions (potassium, sodium and chloride)(8), metabolites (glucose, lactate and urea), proteins (immunoglobulins, enzymes and hormones) and cytokines (interleukins and tumour necrosis factor). These molecules can be used as biomarkers for various diseases or conditions (3, 5, 9).

Some solutes in sweat, such as potassium, have concentrations comparable to those found in blood, while others become relatively diluted due to reabsorption in the duct (e.g., sodium, chloride, and bicarbonate). However, sweat composition is complex and variable. Indeed, various factors have been shown to influence sweat composition, including ethnicity, gender, age, environmental factors, and physical activity (10, 11).

Fresci’s Analytical Insights

A recent analysis of the scientific literature by Laura Avogaro on behalf of FRESCI, has revealed that sweat is the predominant fluid evaluated in wearable devices, with a steady increase in research focus. The analysis comprehensively reviewed over 206 peer-reviewed articles (from 2015 to 2024), focusing particularly on wearable devices. Notably, 195 of these articles examined non-invasive solutions.

A wearable is defined as worn on the body or clothing. It consists of a target receiver and a sensor: the receiver identifies the target analyte and produces detectable responses, while the sensor converts the receiver’s response into a readable signal [12, 13]. Based on their detection principle, sweat sensors can be categorized into three main types: fluorescent, colorimetric, and electrochemical. In FRESCI’s scientific literature analysis, approximately 82% of the devices were based on electrochemical detection.

Wearables offer convenient and rapid detection methods, presenting enormous potential for non-invasive sweat biomarker detection. The development of wearable sweat sensors is pivotal in determining the future popularity and application of sweat detection, as well as the broader development of wearable health electronic devices. In 2013, Jia and colleagues pioneered the integration of flexible materials into sweat sensors in the form of a tattoo, a development that enhanced the comfort of sweat detection and expanded its application in diverse life scenarios. (14).

Subsequent studies consistently identified flexible materials as the dominant wearable sweat sensor substrate. Sweat patches, which are adhesive patches that adhere to the skin to collect sweat, have been widely used to collect sweat secreted by the human body under both basal and stimulated conditions [15-18]. However, the need for prolonged adhesion for adequate sweat collection has been identified as a significant challenge. To address these challenges, researchers have developed Janus electronic textiles or Janus e-textiles (smart textiles that exhibit dual functionality, in reference to the dual-faced Roman god, Janus) using natural silk materials to improve the comfort of long-term sensor wear [19, 20].

iSudorology: The Interdisciplinary Future of Personalised Sweat Analysis and Wearable Health Tech

The introduction of wearable biosensors has been identified as a key development in the field of sweat analysis. The integration of these biosensors with communication modules such as Bluetooth, near-field communication (NFC), Wi-Fi and wireless body area network (WBAN) has enabled wearable healthcare devices to visualise and share data in real-time [21]. These biosensors have been developed to continuously monitor biomarkers by collecting and analysing small amounts of sweat, thereby facilitating early disease detection and personalised treatment [22, 23]. However, given the multidisciplinary nature of sweat analysis, collaboration between different disciplines is needed to advance the field.

In this regard, Brasier and collaborators have proposed the term “iSudorology” to describe this concept [24], which involves diverse expertise in biology and medicine, as well as professionals from engineering, chemistry, materials science and other related disciplines. The development of AI has also improved the efficiency of sweat analysis data, creating opportunities for the development of new algorithms to overcome current limitations and further develop this technology [25]. As the field continues to evolve, iSudorology has the potential to transform non-invasive diagnostics and open new frontiers for personalised and predictive healthcare.

Together, we are witnessing the rapid integration of technology, edging closer to the realm of Augmented Reality. Imagine a seamless network of sensors and signals working in sync, creating an interactive overlay of health insights—whether through smart glasses, smartphone interfaces… or even other innovations yet to come!

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