Spying on the Human Body pt.2

No sweat, no gain.

Leon Wang
StartupReview
5 min readJul 22, 2018

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In the previous article, I gave an overview of the different types of biosensors in development. Today, I will be digging deeper into sweat-based sensors and the cutting edge technologies behind them. As discussed, there are many advantages in using sweat for data collection. Firstly, it is less much less invasive to take sweat samples compared to blood. Additionally, since sweat collection can be a continuous process, biosensors are able to obtain real time information on personal health. In the words of Jason Heikenfeld- director of UC’s Novel Devices Laboratory, “If you do a blood draw, you get one data point.” “In many cases, doctors would love to know if concentrations are increasing or decreasing over time.” However, there are also many major hurdles in the development of sweat-based biosensors:

Image from Google.

We don’t sweat 24/7 (At least you shouldn’t)

Sweating is the body’s natural cooling system. If the body doesn't need to cool down, it doesn't sweat. No sweat, no data. This raises a problem for biosensors that are dependent on collecting continuous data points. As Heikenfeld puts it “People for a long time ignored sweat because, although it can be a higher-quality fluid for biomarkers, you can’t rely on having access to it.”

Inducing Perspiration

One solution is to simply get the patient to sweat when measurements need to be taken. However, while it might be easy to force (or bribe) a graduate student to do a ten minute run on a treadmill, your 70-year old recovering cancer patient might not view very kindly to this request.

Another approach is to induce sweating only at the location of the biosensor (kinda like local vs general anesthesia). Eccrine Systems, an Ohio based startup, does this by sending a tiny electrical charge through the upper layer of skin. This form of electrical stimulation, or iontophoresis, activates sweat glands in that area to produce sweat but causes no discomfort. As of recently, Eccrine Systems has raised more than $3 million in seed funding for this iontophoresis sweat-biosensor. The Air Force Research Lab has also awarded Eccrine $800,000 and is interested in using this technology to monitor hydration and combat-readiness of fighter pilots.

Eccrine System’s technology for stimulating and collecting sweat. Original imaging from Sciencemag.org

Sizing Down

A different approach is to reduce the amount of sweat required to make a measurement. Biosensors could then utilize the tiny amounts of sweat consistently present on skin surfaces. Xsensio is a Switzerland based company that has developed a miniscule “pump” to collect sweat into a super tiny 20 nanometer thick chips, where it is then analyzed. This micro-pump involves two fluidic layers on user’s skin to utilize capillary action in directing sweat up into the chip. This process is continuous and does not require an external power source, allowing for reductions in biosensor size. In order to get useful information out of such small volumes of sweat, Xsensio uses a multilayer modular platform with each layer detecting for a different molecule or biomarker. “By depositing different biochemical layers on each of the miniature sensors, we can measure a host of variables ranging from electrolytes and metabolites to tiny molecules and proteins.” says Esmeralda Megally, CEO of Xsensio. Using this capillary pump technology and ultrathin modular layers, Xsensio claims that the volume of sweat required could be reduced 10,000 fold. So far, Xsensio has over $500,000 in seed funding from investors.

Nanoscale chip developed by Xsensio to measure sweat biomarker levels. Image from EPFL.

Person to Person Variance

Different people sweat differently in different situations. The exact composition of your sweat is essentially a “fingerprint” that belongs to you alone. The contents of your sweat can also fluctuate depending on factors such as your emotions and the time of day. This is a major issue for researchers trying to distill valuable information from sweat samples. “Sweat can provide much of the same useful information about patients as blood. “The problem has always been getting the same consistent sample as is possible with a standard blood draw”- Heikenfeld.

Improved Separation/Isolation Methods

One method to overcome this variance is to develop better isolation methods. Essentially, you physically separate the biomarker stuff you care about from the variable sweat stuff that you don’t really care about. One research group at Stanford university led by materials scientist Alberto Salleo created a patch that can isolate and detect cortisol levels, a major indicator of stress. A molecularly selective membrane in the patch allows for passage of charged ions, like sodium and potassium. Cortisol, however, is blocked and in turn inhibits the flow of other charged ions. The resulting difference in electrical current can then be correlated to determine cortisol concentration.

Onur Parlak, the leading researcher on this project, tested the prototype on several runners and found that patch results matched those from an ELISA assay (enzyme-linked immunosorbent assay) that takes several hours. The full paper describing this new technology can be found here.

Cortisol measuring skin patches from Salleo’s research group. Image from Google.

Machine Learning

Recent advancements in machine learning and artificial intelligence can also be applied to remove normal variances from important signals in sweat. Very surprisingly however, I could not find any startup or research group that is focusing in on this area. While many groups have been using AI/machine learning to isolate important factors in blood samples, the same technology does not seem to be as mature for sweat data. Perhaps, the large and organized data sets that exist for blood data do not exist for sweat (for now). However, I would be very surprised if we don’t see a big player in the sweat biomarker field utilizing AI technology in the coming years.

The Bottom Line:

Sweat has always been the less invasive alternative to blood in terms of biosensor data collection. However, up until recently, there has been limited methods to reliably collect and isolate meaningful data. Innovative technologies such as Eccrine’s iontophoresis sweat induction and Xsensio’s micro-sweat pumps could potentially invigorate a new age of biosensors. With the addition of better filtration devices and AI technology, sweat could replace blood as a new standard in the biological gold rush.

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Leon Wang
StartupReview

Leon is a PhD candidate at Princeton University researching cancer diagnostics and therapy