Microfluidic Sensing- Microfluidic Sweat Sensors- Ryan Lodge

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CHEM-ENG 535: Microfluidics and Microscale Analysis in Materials and Biology

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Background

Microfluidic sweat sensors are a niche subsection of microfluidic biosensors. Microfluidic biosensors are wearable microfluidic devices that interface with the skin to collect and analyze a variety of different biomarkers. Microfluidic sweat sensors specifically measure, monitor and analyze a subject's sweat. The sensor generally consists of a flexible but durable “lab on a chip” style device with a layer of adhesive on the bottom. The concept of wearable sensors is a relatively new idea facilitated by recent advances in technology. Despite these recent advances, a broad spectrum of issues surrounding microfluidic sweat sensors remain unanswered. This leads to a lot of variation in the approach of the design, fabrication and functionality of the devices in research. This page will give a high level overview of some of the issues surrounding microfluidic sweat sensors, and give examples of some proposed solutions being researched and developed.

Applications

Sweat contains a variety of biomarkers that can be analyzed to provide accurate, real-time data about a subject's health. Thus, making the potential of wearable microfluidic sweat sensors extremely lucrative to athletic, military, and clinical health fields. These biomarkers can be analyzed to screen for and diagnose disease, give information about an individual's hydration and electrolyte levels, and give performance feedback to athletes and soldiers. The biomarkers that are most relevant to the clinical health field are the biomarkers that can be analyzed and screen for disease. For example, cystic fibrosis can be diagnosed through the chlorine levels of sweat[7]. Additionally, glucose levels in sweat can provide non-intrusive screening for diabetes[7]. Furthermore, valuable insight on kidney disease can be obtained from uric acid and creatine biomarkers in sweat[7]. A condition called metabolic alkalosis is when soft tissues have elevated pH levels and can be characterized by pH level of sweat[3]. Despite the variety of clinical applications of sweat sensors, the larger market for microfluidic sweat sensors is in the athletics industry and the military. Athletes and soldiers can get real time feedback on their hydration level and performance levels. Specifically, the sodium and chloride concentrations in sweat are directly related to hydration levels. Hydration levels can also be determined by analyzing sweat rate. This is especially important in hot environments as athletes in hot environments have shown inadequate rehydration in comparison to sweat loss[5]. Physical fatigue can be analyzed by looking at lactate levels in sweat[3]. Measuring sweat rate, electrolyte levels and temperature all together can be used to give valuable information about the potential onset of heat exhaustion or heat stroke[3].

Operation/Functionality

Since research into microfluidic sweat sensors is so new, there is a substantial amount of variation in the design and functionality of the microfluidic sweat sensors being researched. However, some general trends can be observed. Most current sweat sensors in research are aimed towards athletic or military application, so the primary method of sweat collection is having a subject exercise and generate sweat naturally. This creates a pressure gradient between the sweat being secreted and the microfluidic channel. Pressure increases at the collection site as more sweat is secreted, driving sweat further into the microfluidic channels of the sweat sensor [2]. Chips can be broken into two main subgroups based on how the sensing is done, optical sweat sensors and electrochemical/electrical sweat sensors.

Optical Sensing

Optical sweat sensors generally function by absorbing sweat into specialized pores and/or channels of the microfluidic chip. These pores are filled with reagents designed to produce a colorimetric response, different reagents can be used to detect different components of sweat. Typically, when there is a high concentration of the component being measured, it produced a strong, vibrant colorimetric response. Additionally, these optical sweat sensors can often be scanned with a smartphone to get accurate analysis of the sweat sensor, or can be loosely analyzed by eye [3]. The main benefits to optical sweat sensors are they are usually low cost, lightweight and relatively simple devices. However, a drawback of most optical sweat sensors is that they cannot track changes is sweat composition over time [3].

Figure 1: Image a person wearing a Gatorade sweat sensor and using the Gatorade app for detailed analysis. Photo taken from gatorade.com using Creative Commons Attribution 4.0 License.

An example of an optical sweat sensor is the Gatorade sweat patch that recently hit the market. This is a lightweight, single use sweat sensor that measures fluid loss, sweat rate and sodium levels to give feedback to athletes. An app is available on all major platforms that can be used to scan the optical sweat sensor and get in depth analysis in seconds. The sensor is about 2.5 x 1.5 inches in size and weighs about 1.25 oz. It is currently sold in two packs for $25. The Gatorade sweat patch is convenient, comfortable and relatively affordable. However, it is only functional between 47-95°F and 20-120 min of exercise[9].

Electrical/Electrochemical Sensing

Electrical/Electrochemical sweat sensors are typically much more complex than optical sweat sensors. They require a power source and an electrical component that present a lot of difficulties when designing something that interfaces with the skin and has to be soft and flexible but also durable. However, electrical sweat sensors allow for long term, continuous measurement of sweat rate and sweat composition. It also allows for real time changes in sweat rate and sweat composition to be measured and recorded.

Figure 2: Diagram of the construction of an electrical sweat sensor studied in research by Nyien et al., under Creative Commons Attribution 4.0 License.

Figure 2 shows an example of an electrical sweat sensor. This sensor is made up of two components, a microfluidic electrochemical component and an electrical component [1]. The electrical component is in the form of a printed circuit board, or a PCB. The microfluidic component is made up of four layers. The top layer as shown in Figure 2 is the microfluidic channel made out of PDMS. The second layer from the top is two gold spirals lay directly below the channels of the microfluidic chip. The purpose of these spirals is to measure the sweat rate via the difference in impedance between the two spirals, magnitude of impedance drops as sweat volume increases. The third layer from the top is an insulation layer made from perylene C. The bottom layer is Na sensing electrodes placed in the center of the sweat collection reservoir such that Na sensing happens simultaneously with sweat accumulation [1].

Fabrication Techniques and Materials

Just as there is variety in the approach to design the chip, there is also variety in the approach of fabricating the microfluidic sweat sensors. The most common fabrication techniques are soft lithography techniques. Specifically, replica molding[5], embossing[6], and photolithography[1] have been used in research. The general process of replica molding used in the fabrication of sweat sensors in research is shown in Figure 3. The process consists of using casting a mold with the desired polymer and solvent and then evaporating the solvent leaving only the polymer behind. Finally, a bottom layer is attached to the top and sealed and then a layer of adhesive is applied to the bottom[5]. Hot embossing is another form of soft lithography that is similar to replica molding. Embossing is when a template is pressed into a polymer to create a desired design. Another form of fabrication seen in literature is photolithography. The general process of photolithography involves placing a mask on top of a light sensitive substrate, and then exposing the masked substrate to light. Depending on the nature of the photoresist the exposed areas of the substrate will either crosslink or dissolve while the masked areas will do the opposite.

Figure 3: Diagram depicting the fabrication process of a microfluidic sweat sensor used in research by Reeder et al., under Creative Commons Attribution 4.0 License.

The most common material used to make microfluidic devices is polydimethylsiloxane (PDMS). PDMS is a favorable material because of its visual transparency, its ability to be formed into a microfluidic chip easily, it is biocompatible, soft and very elastic[6]. However, PDMS is water permeable, making it unfavorable for aquatic use. Therefore, poly(styrene isoprene styrene) (SIS) has been proposed as an alternative. SIS has shown to have very low permeability to water along with the ability to make a watertight adhesion to the skin. SIS is also visually transparent and has low elastic modulus and high elasticity, further making it a viable substitute for PDMS[5]. However, SIS is less easily patterned into microfluidic devices than PDMS.

References

1 Nyein, H. Y. Y.; Bariya, M.; Kivimäki, L.; Uusitalo, S.; Liaw, T. S.; Jansson, E.; Ahn, C. H.; Hangasky, J. A.; Zhao, J.; Lin, Y.; Happonen, T.; Chao, M.; Liedert, C.; Zhao, Y.; Tai, L.-C.; Hiltunen, J.; Javey, A. Regional and Correlative Sweat Analysis Using High-Throughput Microfluidic Sensing Patches toward Decoding Sweat. Sci. Adv. 2019, 5 (8), eaaw9906. https://doi.org/10.1126/sciadv.aaw9906

2 Nyein, H. Y. Y.; Tai, L.-C.; Ngo, Q. P.; Chao, M.; Zhang, G. B.; Gao, W.; Bariya, M.; Bullock, J.; Kim, H.; Fahad, H. M.; Javey, A. A Wearable Microfluidic Sensing Patch for Dynamic Sweat Secretion Analysis. ACS Sens. 2018, 3 (5), 944–952. https://doi.org/10.1021/acssensors.7b00961

3 Choi, J.; Bandodkar, A. J.; Reeder, J. T.; Ray, T. R.; Turnquist, A.; Kim, S. B.; Nyberg, N.; Hourlier-Fargette, A.; Model, J. B.; Aranyosi, A. J.; Xu, S.; Ghaffari, R.; Rogers, J. A. Soft, Skin-Integrated Multifunctional Microfluidic Systems for Accurate Colorimetric Analysis of Sweat Biomarkers and Temperature. ACS Sens. 2019, 4 (2), 379–388. https://doi.org/10.1021/acssensors.8b01218

4 Heikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; Kim, J. Wearable Sensors: Modalities, Challenges, and Prospects. Lab Chip 2018, 18 (2), 217–248. https://doi.org/10.1039/C7LC00914C

5 Reeder, J. T.; Choi, J.; Xue, Y.; Gutruf, P.; Hanson, J.; Liu, M.; Ray, T.; Bandodkar, A. J.; Avila, R.; Xia, W.; Krishnan, S.; Xu, S.; Barnes, K.; Pahnke, M.; Ghaffari, R.; Huang, Y.; Rogers, J. A. Waterproof, Electronics-Enabled, Epidermal Microfluidic Devices for Sweat Collection, Biomarker Analysis, and Thermography in Aquatic Settings. Sci. Adv. 2019, 5 (1), eaau6356. https://doi.org/10.1126/sciadv.aau6356

6 Koh, A.; Kang, D.; Xue, Y.; Lee, S.; Pielak, R. M.; Kim, J.; Hwang, T.; Min, S.; Banks, A.; Bastien, P.; Manco, M. C.; Wang, L.; Ammann, K. R.; Jang, K.-I.; Won, P.; Han, S.; Ghaffari, R.; Paik, U.; Slepian, M. J.; Balooch, G.; Huang, Y.; Rogers, J. A. A Soft, Wearable Microfluidic Device for the Capture, Storage, and Colorimetric Sensing of Sweat. Sci. Transl. Med. 2016, 8 (366). https://doi.org/10.1126/scitranslmed.aaf2593

7 Choi, J.; Ghaffari, R.; Baker, L. B.; Rogers, J. A. Skin-Interfaced Systems for Sweat Collection and Analytics. Sci. Adv. 2018, 4 (2), eaar3921. https://doi.org/10.1126/sciadv.aar3921

8 Li, S.; Ma, Z.; Cao, Z.; Pan, L.; Shi, Y. Advanced Wearable Microfluidic Sensors for Healthcare Monitoring. Small 2020, 16 (9), 1903822. https://doi.org/10.1002/smll.201903822

9 Gatorade sweat patch from gatorade.com https://www.gatorade.com/gear/tech/gx-sweat-patch/2-pack?utm_source=bing&utm_medium=paidsearch&utm_campaign=gatorade_brand_sweatpatch_phrase&utm_content=gatorade_patch_phrase&utm_term=gatorade+sweat+patch&gclid=77cc412ef053197cde16235a989ed9a4&gclsrc=3p.ds&msclkid=77cc412ef053197cde16235a989ed9a4