Approximately 3.5 million of the world's population was diagnosed with advanced staged cancer in 2017. This is just one example indicative of the limitations in today's healthcare systems. The rather reactive medical approaches fail in preventing individuals from obtaining diagnosis and treatment in a timely manner, especially in remote areas and low and middle-income countries, where access to healthcare services has been a challenge due to the lack of resources and medical personnel. Therefore, it is critical to provide solutions to not hinder health assistance due to the shortcomings in either the technology or the resources.
To tackle this challenge, Hnin Yin Yin Nyein, a Ph.D. in the Department of Radiology at Stanford University, developed wearable biosensors which utilize resting sweat as a constant biofluid source for assessing health information at a molecular level. They can be mass-produced in a cost-effective way and allow individuals to continuously and routinely keep track of their health condition.
Sweat is composed of various biomolecules which can be indicative of underlying physiological conditions. Despite sweat composition and secretion behavior have been used as standard clinical biomarkers in pulmonology and neurology, accessing sweat remains an outstanding challenge as low secretion rates and rapid evaporation under an ambient environment limit the amount of fluid that can be reliably collected. Current research on wearable sweat sensing uses physical, thermal, or chemical stimulation to collect a large volume of sweat for analysis. Yet they fail to enable continuous analysis at a frequent and extended period due to the physical fatigue or sweat glands deterioration caused by external triggers. Convenient, wearable devices for continuous sweat monitoring, without active sweat induction, remain a gap in the field.
Hnin's invention of ultralow volume passive sweat biosensors makes sweat a viable mode of health monitoring at a molecular level across activities, whether active or sedentary, and across user groups, whether young or old, healthy or ill. With these sensors, she showed that continuous sweat analysis can be done to study how the body's endogenous sweating response relates to stress, metabolic conditions, and potentially neurological afflictions.
From a technological aspect, her sensors represent the first demonstration of ultralow volume resting sweat at near real-time in-situ analysis. Due to the large hydrophobic collection well in conventional microfluidics for sweat sensing, its functionality is limited to high secretion rates and there is a significant delay between sweat collection and measurement. Hnin's sensors allow rapid uptake at low secretion rates via the incorporation of a rigid hydrophilic filler topped with a thin hydrogel in the collection well. Due to minimal measurement delay after secretion, the sensors push sweat monitoring closer to near real-time while minimizing the time sweat remains on the skin. The sensors also allow digital sweat rate and composition measurement inside the microfluidic channel. The electrochemical sensors allow accurate molecular quantification at a low level with a volume as small as 40 nL and operational stability up to 24 hours. They only require a one-point calibration prior to usage and can be discarded after one-time usage. The patch has a small footprint that allows versatile body placement even at small-area regions like the fingertips and can be mass-produced.
These sensors have been used for longitudinal sweat monitoring over 24-h periods to observe the onset of and recovery from stress. Moreover, the sensors are demonstrated to enable tracking sweat dynamics due to metabolic conditions such as hypoglycemia-induced sweating in diabetic patients and medications-influenced sweat composition changes over an extended period. By monitoring the baseline and deviation due to stress events or physiological changes, it creates opportunities for quantitative continuous monitoring of physical to psychological strain even for impacted populations.
Currently, Hnin has expanded her scope of study to bioassay-based reagentless sensors to enable point-of-care testing and wearable devices to a broader class of drugs, cytokines, and proteins detection. She envisions that, by collecting longitudinal molecular information across individuals with these devices, we can survey and identify what may be relevant to physiological changes. Through integration with mobile technology, users can share first-hand information with healthcare providers for promptly monitoring individuals' well-being. Therefore, her invention represents a crucial advancement for non-invasive probing of our body at molecular levels for continuous or routine health assessment for diverse applications toward more personalized, predictive, and proactive healthcare.
