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Yang, M.; Sun, N.; Lai, X.; Zhao, X.; Zhou, W. Sampling of Non-Electrochemical Sweat Sensors. Encyclopedia. Available online: (accessed on 17 June 2024).
Yang M, Sun N, Lai X, Zhao X, Zhou W. Sampling of Non-Electrochemical Sweat Sensors. Encyclopedia. Available at: Accessed June 17, 2024.
Yang, Mingpeng, Nan Sun, Xiaochen Lai, Xingqiang Zhao, Wangping Zhou. "Sampling of Non-Electrochemical Sweat Sensors" Encyclopedia, (accessed June 17, 2024).
Yang, M., Sun, N., Lai, X., Zhao, X., & Zhou, W. (2024, January 03). Sampling of Non-Electrochemical Sweat Sensors. In Encyclopedia.
Yang, Mingpeng, et al. "Sampling of Non-Electrochemical Sweat Sensors." Encyclopedia. Web. 03 January, 2024.
Sampling of Non-Electrochemical Sweat Sensors

Sweat, commonly referred to as the ultrafiltrate of blood plasma, is an essential physiological fluid in the human body. It contains a wide range of metabolites, electrolytes, and other biologically significant markers that are closely linked to human health. Compared to other bodily fluids, such as blood, sweat offers distinct advantages in terms of ease of collection and non-invasive detection. 

human sweat non-electrochemical sensing microfluidic samplin

1. Introduction

Sweat contains a variety of biomarkers, including metabolites [1], electrolytes [2], trace elements [3], and small amounts of macromolecules [4], and there is a strong correlation between human sweat and blood [5][6][7]. Analyzing sweat offers a non-invasive means for health assessments and disease diagnoses. For instance, cystic fibrosis can be diagnosed based on sweat chloride concentration [8], and indirect assessment of blood glucose concentration can be made based on sweat glucose concentration [9], while the hydration status of the human body can be determined based on the concentration of potassium and sodium ions in sweat [10]. As such, detecting sweat biomarkers has garnered significant attention in recent years, yielding impressive research outcomes.

2. Paper-Based Sampling of Non-Electrochemical Sweat Sensors

Paper-based materials are rich in hydrophilic groups, such as carboxyl and hydroxyl groups, and are endowed with numerous capillaries, enabling them to spontaneously transport liquids and achieve fluid flow in a specific direction without requiring external pumping [11][12][13]. Additionally, paper-based materials are cost-effective and biodegradable, thus serving as a commonly employed material for microfluidic devices.
Due to their soft and pliable nature, paper-based materials are easy to cut and fold [14]. Utilizing paper-cutting techniques to create geometric patterns, fluids can flow along these patterns. Geometric-patterned paper-based channels, such as S-shaped and mesh patterns, can also conform to skin deformation [15][16]. For instance, Mogera et al. [15] created an S-shaped fluid channel by cutting filter paper. Liquid is conveyed to each detection area via the capillaries present in the paper. The S-shaped design enables the paper material to possess extensibility, which adapts to the curvature of the skin surface without breaking. Similarly, Gao et al. [16] cut filter paper into a fish-shaped pattern, resulting in patterned filter paper with high stretchability that forms multiple branching channels. Sweat is collected at the fish tail and transferred through the fish-scale mesh structure on the fish belly, eventually converging at the monitoring area, i.e., the fisheye.
Paper-based materials contain numerous tiny capillaries, which allow for spontaneous liquid transport. The liquid transport capabilities of paper-based materials with different pore sizes vary, with smaller pore sizes resulting in weaker fluid transport and slower liquid flow rates. Vaquer et al. [17] cut filter paper into a rectangular paper strip with a circular detection area at the end. Depending on the spontaneous transport of sweat, enzymes are transported to the detection area with the color reagent. Filter paper with larger pore sizes has a higher liquid flow rate, ensuring that the enzyme level reaches the detection area adequately, resulting in a higher sensitivity of the colorimetric device. The separation of enzymes from the color reagent avoids spontaneous color response between enzymes and chromogens, thereby reducing the background signal of glucose detection.
The wax printing technique is a useful method for constructing microchannels on paper-based materials by creating hydrophobic barriers [18][19]. The surface of the paper-based material can be modified by using hydrophobic substances such as wax, polydimethylsiloxane (PDMS), or graphite, which penetrate into the micro-pores of the paper during high-temperature baking to block fluid channels and form hydrophobic barriers [20][21][22]. As a result, sweat will flow along the unprinted hydrophilic areas. Zhang et al. [23] printed carbon powder on filter paper to create a microfluidic pattern. Upon heating, the carbon powder penetrates the micro-pores of the paper-based material, forming hydrophobic barriers on the hydrophilic material. Colorimetric reagents are then applied to the designated area of the filter paper. When sweat glands secrete sweat, the capillary force generated by the cellulose in the filter paper absorbs and transports the sweat along the microfluidic channel to the detection area, where a colorimetric method measures the glucose, pH, and lactate of sweat. Similarly, Lopez-Ruiz et al. [24] coated ink on the surface of the filter paper to construct a microfluidic channel. Weng et al. [25] used the screen-printing process to print PDMS on the surface of the filter paper and prepared a 3D microfluidic paper folding device by simple cutting and folding. The device has four layers: the bottom layer collects sweat, the transmission layer delivers sweat, the reaction layer provides a reaction zone for the target substance, and the covering layer evaporates sweat and blocks contaminants. The device is used for fluorescence analysis of the target substance by taking pictures of the reaction layer with a smartphone.
Paper-based materials are characterized by numerous capillaries with different pore sizes, resulting in varying liquid flow rates. The paper can be easily modified by cutting or using the wax printing technique to create hydrophobic channels, which guide sweat to flow along the desired path. Due to their lightweight, thin, and soft properties, paper-based materials can be in close contact with the human body and resist damage caused by bending. In addition, the low cost and simple processing of paper-based materials make them widely used in the production of wearable devices.

3. Thread-Based Sampling of Non-Electrochemical Sweat Sensors

The thread is formed by wrapping multiple strands of fine wire, and the gaps between the wrapped threads can serve as capillary channels for fluid transport [26]. Compared with paper-based materials, threads have stronger toughness and can be easily obtained from natural or artificial materials. Threads have advantages, such as being lightweight, breathable, durable, and low cost, and are widely used in the field of microfluidic sensors.
The surface and fiber walls of natural cotton fibers contain wax, which cannot be wetted by liquids. Alkaline solutions can be used to remove the natural wax on the surface of the thread and enhance its hydrophilicity. Ardalan et al. [27] used a pure alkaline solution to remove the wax from the surface of the thread, which served as the channel for collecting and transferring sweat in microfluidic devices. The thread was connected to the human body with medical double-sided tape, with the front end of the thread in contact with the human skin. When sweat glands secrete sweat, the thread quickly absorbs the sweat and transports it to the detection area at the end. By using embroidery techniques to connect hydrophilic threads with hydrophobic fabrics, the hydrophilic threads transport liquid, while the hydrophobic fabrics prevent the liquid in the threads from flowing outside. Zhao et al. [28] used embroidery techniques to sew hydrophilic threads into hydrophobic fabrics, and fixed the colorimetric paper to the hydrophobic fabric. The hydrophilic thread collected and transported sweat to the detection area, and the hydrophobic fabric prevented the liquid in the hydrophilic thread from leaking. Since alkaline solutions may damage the fibers in the thread, Xiao et al. [29] used specially made hydrophilic threads as fluid channels. Two hydrophilic threads were twisted into a Y shape, with one end connected to the sweat storage cotton pad and the other end connected to the colorimetric filter paper. The remaining end of the twisted thread was passed through the tape, connecting the sweat storage pad with other components, such as the colorimetric filter paper. Sweat was collected by the sweat storage cotton pad and transported to the colorimetric area through the twisted hydrophilic thread.
By utilizing capillary channels between tightly-wound filaments, liquids can be transported, but the pumping ability of capillary force alone is limited. Researchers use external pumps to achieve continuous flow of liquids on fabric or use surface tension at microfluidic interfaces to drive droplet movement. Curto et al. [30] use a water-absorbing pad to provide external power to thread-based microfluidic devices, accelerating the flow rate of liquid inside the thread-based microfluidic device. Hydrophilic threads collect sweat and sequentially transport it to the detection pad and the water-absorbing pad. The water-absorbing pad has high water absorption and, when the liquid in the thread contacts the water-absorbing pad, it quickly absorbs the liquid from the thread and evaporates it to the outside, forming a continuous flow of liquid, which continuously updates the liquid in the detection area. Surface tension at microfluidic interfaces can drive droplets. Xing et al. [31] use the surface tension of droplets to drive them. Hydrophilic threads are sewn onto hydrophobic fabric to create the inlet, fluid channel, and outlet. The inlet is double-stitched onto the fabric, while the fluid channel and outlet are single-stitched onto the fabric. The liquid is collected at the inlet and transported to the outlet. Due to the difference in surface tension between the hydrophilic and hydrophobic interface, the droplet with higher internal pressure will move towards the lower internal pressure side, i.e., the droplet moves from the inlet to the outlet, accelerating the flow of the liquid. Thread contains numerous capillaries, allowing for the transport of liquids. By sewing hydrophilic threads onto hydrophobic fabric, the thread can simultaneously fix various components of the fabric while transferring the liquid. While the capillary force of thread has limited ability to transfer liquid, it has the advantages of low cost and easy stretch, making it widely used in the field of microfluidics.

4. Sampling of Non-Electrochemical Sweat Sensors Based on Microfluidic Valves

Paper-based and thread-based sensors have advantages, such as low cost and flexibility, but they are prone to the mixture of old and new sweat, which greatly reduces the accuracy of the sensor [32][33]. With the development of microfluidics, using microvalves with different functions in microfluidic devices can control the direction of liquid flow, accurately control the sampling volume, avoid liquid mixing, and achieve timed sampling [34][35][36]. Typical microfluidic valves include capillary bursting valves (CBVs), superabsorbent polymer (SAP), and hydrophobic valves.
CBVs are based on the surface tension of water molecules. When the microchannel of liquid flow suddenly expands, the existence of capillary resistance traps the half-moon of the liquid on the valve, and as the pressure continues to increase, when the pressure is greater than the capillary resistance, the liquid continues to flow forward, and at this time, the valve ruptures. Different valve heights, widths, and outlet angles have different burst pressures (BP), as shown in the following formula [37]:
BP = 2 σ ( cos θ I * w + cos θ A h )
where σ is the surface tension of the liquid, 𝜃I is the minimum value between 𝜃A+𝛽 and 180°, where β is the outlet angle and 𝜃A is the contact angle of the liquid on the channel, and w and h are the width and height of the channel, respectively. When the fluid pressure exceeds the BP, the CBV ruptures. Choi et al. [37] designed a colorimetric sweat sensor with multiple reaction zones based on CBVs. Sweat enters the reaction zone through the inlet and successively passes through CBVs #1 and CBVs #2, filling chambers 1 and 2 with sweat, then CBVs #3 passes through, and sweat flows to the next reaction zone. When all the reaction zones are completely filled, CBVs #4 passes through, and waste is discharged from the microfluidic device. The combination of multiple CBVs enables the simultaneous, independent, and real-time evaluation of multiple biomarkers by a single device. Similarly, Zhang et al. [38] used CBVs with two different BPs to achieve sequential sweat sampling. The BP of CBVs #1 is smaller than that of CBVs #2. Sweat enters the device through the inlet, filling three circular detection chambers successively. As sweat is continuously pumped in, the pressure gradually exceeds the BP of CBVs #2, and CBVs #2 passes through, discharging waste.
A non-electrochemical sweat sensor based on microfluidic valves utilizes SAP with high expansion coefficients. When a suitable amount of polymer is placed in a microfluidic chamber, it forms a polymer valve. When liquid enters the chamber, the polymer expands upon contact with water, filling the microfluidic chamber and blocking the fluid flow path. Kim et al. [39] proposed a microfluidic device for measuring the concentration of ammonia and ethanol in sweat based on SAP. When sweat enters the SAP chamber, the polymer absorbs water and expands, pushing the solution above into the detection zone while blocking the microfluidic channel to prevent backflow of the sample and contamination. Similarly, Kim et al. [40] proposed a microfluidic device that combines SAP and hydrophobic valves to measure sweat rate and chloride. Hydrophilic channels with positive capillary force draw sweat into channel 1, but the presence of a hydrophobic valve directs the sweat to channel 2, where the detection zone is located. After filling the detection zone, sweat continues to flow to the SAP, where the polymer expands to block the fluid path, and the sweat flows into channel 3.
Microchannels in microfluidic devices are on the micrometer scale. Hydrophilic channels have a positive capillary force that draws sweat into the microchannels, while hydrophobic channels have a negative capillary force that suppresses liquid entry [41][42][43]. Partial hydrophobic modification in the hydrophilic channel forms a hydrophobic valve that can control the liquid flow direction. Zhang et al. [44] proposed a microfluidic device for timed sampling of sweat using hydrophobic valves. The device is made of PDMS and has three collection chambers (T1, T2, and T3). PDMS has natural hydrophobicity and is partially modified with hydrophilic treatment in some microchannels and collection chambers. The unmodified part of the microchannel remains hydrophobic, forming a hydrophobic valve. When sweat glands secrete sweat, the positive capillary force draws sweat into the microchannel. The hydrophobic valve causes the sweat to flow along the chamber wall and fill the collection chamber. As sweat continues to be secreted, the hydrophobic valve opens, and the sweat flows to the next chamber.
Capillary valves are based on the tension of water, which can change the width, height, and exit angle of channels to create valves with different BPs. SAP valves rely on the swelling properties of the polymer to block microfluidic channels, forcing a change in the direction of the fluid flow. Hydrophobic valves use capillary force to promote liquid flow in hydrophilic walls and prevent flow in hydrophobic walls, causing liquid to flow along the hydrophilic wall. The use of valve structures can guide sweat into the microchannels for timed sampling, avoid liquid mixing, and achieve accurate and timed analysis of sweat.


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