How Sweat Sensors Work

Sweat Sensors

With many advantages compared to other bodily fluids, including urine and blood, sweat is being increasingly utilized for detecting analytes. Compared to other bodily fluids, collection of sweat is notably non-invasive and readily available which allows for increased detection accuracy with continuous measurement and preservation of analytes. The patent discussed in this post covers a fluid sensing device with the ability to collect a fluid sample and further concentrate the sample with respect to a target analyte. The device can then measure specific concentrations and detect changes in molarity to accurately correlate this data to physiological conditions. [1]

The main claim of this patent regards the concentrating component of the device. Other claims within this patent include a collector reservoir as well as a transport channel connecting the reservoir to the concentrating component. Several mechanisms are proposed to concentrate the fluid, including a pump to draw the fluid through a selective membrane as well as a density gradient with pores (Figure 1,2).This device also has the ability to induce sweat generation with an iontophoresis electrode. Within the device, an osmolarity sensor measures molarity of the collected fluid while a flow rate sensor measures sweat rate. The concentration of specific analytes are measured by sensors specific for those analytes. [1]

Who Uses It?

Sweat sensors were originally used to aid in detection and diagnosis of diseases, including cystic fibrosis and hyperparathyroidism, and became useful for drug monitoring and treatment. [2] These sensors are extremely useful in athletics to measure water loss and can indicate performance by analyte concentration. Sodium and chloride ion analytes can determine hydration status and monitor fluid loss during and after exercise. Hypohydration, in which the sweat rate is greater than water intake, induces antidiuretic hormone release to retain water, often resulting in decreased cardiac output, increased body temperature with reduced sweating, and decreased aerobic performance with increased glycogen breakdown to increase water availability. [3] Other electrolytes such a potassium ions can be measured to indicate muscle cramping or cardiovascular irregularities. Metabolites can also be measured, including lactate and glucose, to measure energy reserves and assess performance or fatigue.

Understanding How It Works

This invention proposes several mechanisms to concentrate a particular analyte in a biofluid such as sweat. The main mechanism uses a selective membrane in which the analyte sensor is surrounded by an immiscible material (Figure 1). For example, if the material is hydrophobic, only hydrophobic solutes in sweat could passively diffuse into the material, thus increasing the concentration of these selective solutes. This patent also includes the incorporation of a gradient in density or pore size corresponding to the direction of flow (Figure 2). In this case, the pore size corresponds to the size of the target analyte. As the pore sizes decrease, the analyte will become concentrated.

Figure 1. Sweat sensor with a selective membrane (655) within the microfluidic channel (680). The analyte sensor (620) contacts the concentrated target analyte. [1]

Figure 2. Illustration of increasing density in the direction of fluid flow (1401) to concentrate the fluid with respect to target analytes. [1] 

The distribution coefficient of the target analyte can be experimentally measured. As the target analyte molarity is equivalent to this coefficient, the concentration of the target analyte can be determined. [1] To determine the rate at which this analyte is leaving the body through sweat, including accounting for evaporation. The following equation can determine the diffusion coefficient [4]:

D=2PL/K, where

 D= diffusion coefficient
P = solute permeability of membrane
L= thickness of membrane
K= distribution or partition coefficient

Knowing the diffusion coefficient is helpful to then determine the rate at which the target analyte is leaving the body through diffusion, accounting for factors like evaporation, by using Fick’s First Law [5]:

To determine the molarity of specific analytes, reference analytes can be used to ensure the sensors are able to accurately detect the target analyte (Figure 3).  The concentration of analytes unaffected by sweat rate, like K+, can be measured to indicate when a sufficient concentration of the target analyte can be measured.

Figure 3. Analyte measurements. Analytes with consistent concentration can be used as a reference to indicate changes in the concentration of another analyte. This ensures the concentration of the target analyte is sufficient enough for the sensor to accurately detect. In window 1, changes in potassium ion concentration are used as a reference for changes in BNP. Window 2 illustrates using changes in albumin, since it’s concentration is consistent, to indicate changes in BNP. [1]

Unique Features

While other inventions have focused on sweat collection methods, including removable absorbent pads to collect sweat (patent US4190060A), this device is the first to utilize concentration techniques to increase accuracy of detection. Other sweat sensors use similar osmolarity techniques to direct sweat from the skin into the sensor (patent US4756314A), but don’t utilize this method within the sensor for analysis.

This device attempts to improve limitations of previous sweat sensors by increasing accuracy of detection for analytes, even when they are diluted. For example, blood glucose is approximately 100 times more dilute in sweat than in blood, so concentrating this analyte can increase ability for detection. [6] With future developments in transport kinetics and understanding lag times of analyte diffusion in sweat, sweat sensors may continue to pioneer the way for detection of analytes in biofluids. [7]

Specific Patent Information

  1. Patent Title: Devices Capable of Fluid Sample Concentration for Extended Sensing of Analytes
  2. Patent Number: US 10,506,968 B2
  3. Patent Filing Date: April 30, 2018
  4. Patent Issue Date: December 17, 2019
  5. Time to Issue: 1 year 7 months 17 days
  6. Inventor(s): Jason Heikenfeld, Jacob Bertrand, Michael Brothers, Andrew Jajack
  7. Assignee: Eccrine Systems, Inc; University of Cincinatti
  8. U.S. Classification: A61B5/4266; A61B10/0012; A61B10/0064; A61B5/0004; A61B5/14517; A61B5/14521; A61B5/14532; A61B5/14546; A61B5/1468; A61B5/6833; A61F13/0246; G01N33/50; G01N33/5308; G01N33/5438; G01N33/66; A61B2010/0016; A61B5/0002
  9. Number of Claims: 10 claims

References

  1. Heikenfeld et al. (2019). Devices Capable of Fluid Sample Concentration for Extended Sensing Analytes. U.S. Patent No. 10,506,968 B2. U.S. Patent and Trademark Office.
  2. Choi D-H, Thaxton A, Cheol Jeong I, et al. Sweat test for cystic fibrosis: Wearable sweat standard sensor vs. standard laboratory test. J Cyst Fibros. 2018:35-38. doi:10.1016/j.jcf.2018.03.005
  3. Huang X, Liu Y, Chen K, et al. Stretchable, Wireless Sensors and Functional Substrates for Epidermal Characterization of Sweat. Small. 2014;10(15):3083-3090. doi:10.1002/smll.201400483
  4. Sonner Z, Wilder E, Heikenfeld J, et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. doi:10.1063/1.4921039
  5. Wang Y, Gallagher E, Jorgensen C, et al. An experimentally validated approach to calculate the blood-brain barrier permeability of small molecules. doi:10.1038/s41598-019-42272-0
  6. Chung M, Fortunato G, Radacsi N. Wearable flexible sweat sensors for healthcare monitoring: A review. J R Soc Interface. 2019;16(159). doi:10.1098/rsif.2019.0217
  7. Seshadri DR, Li RT, Voos JE, et al. Wearable sensors for monitoring the physiological and biochemical profile of the athlete. doi:10.1038/s41746-019-0150-9
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One thought on “How Sweat Sensors Work

  1. This device attempts to improve limitations of previous sweat sensors by increasing accuracy of detection for analytes, even when they are diluted.

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