Wearable Sweat Sensor: Detecting the Molecular Hallmark of Inflammation

Recently, researchers from CalTech published their findings on a newly developed wearable graphene sensor capable of detecting inflammation at its early stages. Inflammation can be classified into two types: acute and chronic. Acute inflammation is a short-term response that typically resolves in two weeks or less. It is usually beneficial and helps the body fight off infections and heal wounds. Chronic inflammation, on the other hand, lasts for months or even years. It occurs when the immune system's response does not completely eliminate the cause of inflammation, leading to prolonged tissue damage. Chronic inflammation is associated with various diseases, including heart disease, diabetes, and cancer.

What challenges does inflammation present, what did the researchers demonstrate, and how could it be important in future health monitoring applications? 

What challenges does inflammation present?

As much as we may hate it, inflammation is crucial for the healing process, which is why the body does it. Simply put, when foreign pathogens and/or infection is detected, the immune system will flood that area with white blood cells, blood, and all other manner of destructive compounds with the sole aim of clearing the infection and removing necrotic tissue. 

To make sure that this concoction of death does its job effectively against infection, the body also triggers the swelling of blood vessels, which also increases the heat of the area. But, for all the benefits that inflation provides, they can also be problematic for sufferers and, in some cases, extremely dangerous.

As inflammation causes swelling, it can be very painful to the touch, causing massive amounts of discomfort. While swelling can be partly managed with medication (such as ibuprofen), serious swelling can be difficult to control, and if it becomes too severe, it can lead to health complications. For example, inflammation can introduce the risk of additional infection, effectively rendering the initial response to an infection mute. Inflammation can also damage tissue to the point where it scars, and this can lead to reduced organ functionality (this is particularly an issue for lungs).

Over long periods of time, chronic inflammation can lead to other complications, including heart disease, rheumatoid arthritis, and even cancer. As such, it is always important to identify inflammation as early as possible, especially in organs and deep tissue where it may be less obvious.

To further understand the medical implications of inflammation, it's important to note that inflammation is a natural response of the body to injury or infection. However, when inflammation becomes chronic, it can lead to serious health issues such as heart disease, rheumatoid arthritis, and even cancer. This is why early detection of inflammation is crucial. 

CalTech researchers develop wearable sensors capable of detecting inflammation

Recognising the challenges faced with inflammation, researchers from CalTech recently published their findings on a newly developed wearable sensor capable of identifying early stages of inflammation in the body. The sensor, installed on a flexible substrate powered by a small battery, is capable of being stuck onto the body while having little effect on the user and uses non-invasive technologies to detect inflammation, reducing the health risks posed by frequent blood tests.

In order to detect inflammation, the researchers recognised that they needed to be able to detect a specific protein called C-Reactive Protein (CRP). This molecule is secreted by the liver during times of inflammation and will find its way into sweat. However, while the presence of CRP indicates inflammation, it is not easy to detect due to the large size of the molecule. This large size not only sees concentrations in the blood significantly reduced but also makes it harder for the protein to get into sweat. As such, any sensor looking for this protein has to be able to detect trace amounts.

To get around this issue, the researchers created a sensor based on graphene using laser-etching to form a specialised shape and texture. This graphene sensor was further impregnated with many tiny pores that increased the surface area of the sensor, thereby increasing its sensitivity.

Graphene, a single layer of carbon atoms arranged in a two-dimensional honeycomb lattice, is an ideal material for this type of sensor due to its exceptional electrical conductivity, flexibility, and biocompatibility. The sensor's ability to detect CRP in sweat is a significant achievement because sweat is a complex fluid that contains a variety of substances, including salts, hormones, and metabolites. The sensor's ability to selectively detect CRP in this complex mixture demonstrates its high specificity and sensitivity.

As stated in the Nature article, 'A wearable electrochemical patch for the real-time monitoring of the biomarker C-reactive protein in sweat detects elevated concentrations of the protein in patients with acute or chronic inflammation.' This highlights the importance and potential of the wearable sensor developed by the CalTech researchers. 

To make the sensor selectively detect CRP, the pores were embedded with antibodies that bind to CRP and the redox molecules resulting from that reaction. This generates a small electric current which can be detected by the graphene sensor. The sensor also integrated gold nanoparticles that include a secondary set of CRP antibodies, and these are used as a signal amplifier such that when a single molecule comes in contact with the graphene sensor, it binds to both the nanogold particles and the CRP antibodies, causing increased electrical activity.

Finally, to account for different body types, the sensor also incorporates pH sensors, ion sensors, and a temperature sensor which are used to adjust the results. The resulting sensor was shown to be effective at detecting CRP and showed a clear correlation with readings taken from blood samples.

For those interested in delving deeper into the research, the findings were published in a Nature article and a CalTech news release. 

How could such sensors help with future health monitoring?

The sensor developed by CalTech is especially important for the field of medical wearables for two reasons. The first is that it was demonstrated to be able to reliably record levels of CRP, meaning that patients can be monitored for signs of infection without needing invasive tests. This also means that patients can be actively monitored, giving medical staff a good understanding of changes in a patient's body.

The second reason is that the sensor developed includes advanced electronics, all on a tiny flexible board that is practical to wear. By using a small coin cell, the researchers demonstrated a practical device that could very well be used in a real-world medical environment, unlike the many sensors and devices that are typically demonstrated by researchers. 

Of course, the sensor will need more research and development to improve its capabilities, increase the battery life, and correlate skin conditions with recorded data. But considering what the researchers have already demonstrated, this sensor could very well be developed into a usable product in the near future, providing medical staff with active monitoring of patients and catching complications before they arise.

 As Wei Gao, the assistant professor of medical engineering who led the development of the sensor, explains, 'This is a general platform that lets us monitor extremely low-level molecules in our body fluids. We hope to expand this platform to monitor other clinically relevant protein and hormone molecules. We also want to see if this can be used for chronic disease management. Inflammation means a risk for many patients. If they could be monitored at home, their risk can be identified, and they can be given timely treatment.' source 

The potential applications of the graphene sensor extend beyond the medical field. For instance, athletes could use the sensor to monitor their inflammation levels during training and recovery. In the military, soldiers could use the sensor to detect early signs of infection or injury. In elderly care, the sensor could provide a non-invasive way for caregivers to monitor the health of their patients.