Stress Levels Revealed in Micro-Beads of Sweat

New sensor needs just two microliters of perspiration

4 min read
Enlisense sweat sensor watch on person's wrist
BARDA

Sweat analysis isn't new: the dynamic chemical composition of perspiration has inspired researchers from elite athletic performance specialists to chronic disease experts to try to decipher its signals.

But translating raw perspiration into "sweat equity" in real time in everyday life is not an easy task. Sometimes climatic conditions don't lend themselves to creating enough sweat to analyze. Sometimes the heightened level of activity necessary to get enough sweat produces chemical changes in the fluid that aren't indicative of a subject's true state. And sometimes, a person is physically unable to create sufficient sweat volumes to analyze with existing technologies.

This problem is especially challenging in the study of stress response in "normal" routines or among those rendered inactive with chronic diseases. Cortisol level is one widely accepted principle in gauging the amount of physiological and cognitive stress someone is experiencing at a given time, but it has been hard to translate that principle into practice outside controlled conditions.

A highly accurate yet comfortable sensor, now in proof-of-concept trials on human subjects in real-world conditions, might be a critical component of systems that will successfully address those obstacles.

Reading off a person's glucose and cortisol levels is the goal. Fortunately, sweat sensors may yet be up to the job.

The technology, developed by Dallas-based EnLiSense LLC and the University of Texas at Dallas, is promising enough that the U.S. government's Biomedical Advanced Research and Development Authiority (BARDA), featured it in its July 2021 innovation highlights. The patch, just 120 square millimeters, can detect target biomarkers in sweat volume as low as 1 to 3 microliters.

Same but different as CGM

Continuous glucose monitoring (CGM) devices such as the Abbott Freestyle Libre and Dexcom G6 might be the most familiar examples of real-time microfluidic monitoring. EnLiSense CEO and co-founder Sriram Muthukumar explained EnLiSense's technology and marketing strategy in comparison to them.

CGMs work, he says, by analyzing changes in interstitial fluid surrounding the body's cells. They do not measure blood glucose directly.

"They use a microneedle that penetrates the skin and uses capillary action to harvest interstitial fluid around the vein," Muthukumar says. "So if the value of the blood glucose is x, the value of the interstitial fluid will be y. I don't care about the absolute values as long as I can predict the trend of the change in x to the change in y. The CGMs use the changes in y to say whether you are in a green zone or not, like driving in a lane. Are you steering too far right or left, are you getting into a hypo- or hyperglycemic state?"

The premise behind the EnLiSense sensor, branded the SweatSenser, is the same, he said. However, CGMs measure that gradient as a current through a kind of electrochemical process called amperometry—in which ions in solution are detected electrically. And this amperometry trick works for sensing glucose, Muthukumar says. But for substances that do not carry a charge or have a minimal charge, cortisol among them, Muthukumar says such an approach does not work.

So the EnLiSense sensor uses an application of Faraday's law of induction that harnesses electrical measurements to infer chemical properties of a system, called electrochemical impedance spectroscopy (EIS). EIS can employ two types of sensors—either a faradaic sensor, which uses reduction/oxidation (redox) reagents in its electrolyte solution, or a nonfaradaic sensor, which does not. The EnliSense cortisol sensor uses the nonfaradaic approach, because it allows for the detection of subtle changes in biomarker levels at very small volumes.

The sensor, which can be worn on a watch-like strap or other non-obtrusive device, is also capable of housing detection strips for more than one target at a time, and has no microneedle that can cause discomfort, such as a CGM.

Complementary closed-loop research

University of Houston researcher Rose Faghih is eager to have access to the EnLiSense sensor. Faghih is running experiments on stress reaction and control using skin conductance response (SCR), the measurable result of electrical characteristics derived from the change in sweat gland activity as stressors change. Faghih is investigating closed-loop systems that can infer cognitive stress levels and offer real-time behavioral suggestions. For instance, she says in a smart home setting, a closed-loop system could measure a resident's stress levels and correspondingly change the level of light or music to suit their mood. Having real-time cortisol sensor data to add context to SCR data would be a boon to her research, she says.

There are even indications this technology could unlock new kinds of treatments for obesity.

"I focused on analyzing cortisol data during my Ph.D. and have a lot of experience with it," she says. "All the cortisol data I have worked with is basically blood samples taken every 10 minutes. I very much hope these will become commercially available, or available through collaborations so I can work with these researchers and use cortisol to infer more information about the brain state."

The EnliSense has already been successfully tested in simultaneous detection of cortisol and glucose in a typical workday scenario on 10 subjects in EnLiSense co-founder Shalini Prasad's UTD labs. The interaction of the two substances might unlock treatments for obesity; Faghih has done similar work on the interactions of cortisol and leptin.

Don't Sweat It! Passive Sweat Detection for Continuous Metabolitewww.youtube.com


Real-world diagnoses will mandate these multi-marker capabilities, Muthukumar says, but might also provide a vital reference point versus the already widely used CGM technology as the company ramps up its market strategy.

"The FDA panel will look for a predicate," he says. "The platform can do more than glucose, but that glucose measurement assures us we can do a reference correlation to Abbott's platform. When I looked at the documentation on which they got FDA approval, that data is so noisy. I'm very confident that I can ask the FDA, 'If you approved them, what is stopping you from approving me?'"

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The Inner Beauty of Basic Electronics

Open Circuits showcases the surprising complexity of passive components

5 min read
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A photo of a high-stability film resistor with the letters "MIS" in yellow.
All photos by Eric Schlaepfer & Windell H. Oskay
Blue

Eric Schlaepfer was trying to fix a broken piece of test equipment when he came across the cause of the problem—a troubled tantalum capacitor. The component had somehow shorted out, and he wanted to know why. So he polished it down for a look inside. He never found the source of the short, but he and his collaborator, Windell H. Oskay, discovered something even better: a breathtaking hidden world inside electronics. What followed were hours and hours of polishing, cleaning, and photography that resulted in Open Circuits: The Inner Beauty of Electronic Components (No Starch Press, 2022), an excerpt of which follows. As the authors write, everything about these components is deliberately designed to meet specific technical needs, but that design leads to “accidental beauty: the emergent aesthetics of things you were never expected to see.”

From a book that spans the wide world of electronics, what we at IEEE Spectrum found surprisingly compelling were the insides of things we don’t spend much time thinking about, passive components. Transistors, LEDs, and other semiconductors may be where the action is, but the simple physics of resistors, capacitors, and inductors have their own sort of splendor.

High-Stability Film Resistor

A photo of a high-stability film resistor with the letters "MIS" in yellow.

All photos by Eric Schlaepfer & Windell H. Oskay

This high-stability film resistor, about 4 millimeters in diameter, is made in much the same way as its inexpensive carbon-film cousin, but with exacting precision. A ceramic rod is coated with a fine layer of resistive film (thin metal, metal oxide, or carbon) and then a perfectly uniform helical groove is machined into the film.

Instead of coating the resistor with an epoxy, it’s hermetically sealed in a lustrous little glass envelope. This makes the resistor more robust, ideal for specialized cases such as precision reference instrumentation, where long-term stability of the resistor is critical. The glass envelope provides better isolation against moisture and other environmental changes than standard coatings like epoxy.

15-Turn Trimmer Potentiometer

A photo of a blue chip
A photo of a blue chip on a circuit board.

It takes 15 rotations of an adjustment screw to move a 15-turn trimmer potentiometer from one end of its resistive range to the other. Circuits that need to be adjusted with fine resolution control use this type of trimmer pot instead of the single-turn variety.

The resistive element in this trimmer is a strip of cermet—a composite of ceramic and metal—silk-screened on a white ceramic substrate. Screen-printed metal links each end of the strip to the connecting wires. It’s a flattened, linear version of the horseshoe-shaped resistive element in single-turn trimmers.

Turning the adjustment screw moves a plastic slider along a track. The wiper is a spring finger, a spring-loaded metal contact, attached to the slider. It makes contact between a metal strip and the selected point on the strip of resistive film.

Ceramic Disc Capacitor

A cutaway of a Ceramic Disc Capacitor
A photo of a Ceramic Disc Capacitor

Capacitors are fundamental electronic components that store energy in the form of static electricity. They’re used in countless ways, including for bulk energy storage, to smooth out electronic signals, and as computer memory cells. The simplest capacitor consists of two parallel metal plates with a gap between them, but capacitors can take many forms so long as there are two conductive surfaces, called electrodes, separated by an insulator.

A ceramic disc capacitor is a low-cost capacitor that is frequently found in appliances and toys. Its insulator is a ceramic disc, and its two parallel plates are extremely thin metal coatings that are evaporated or sputtered onto the disc’s outer surfaces. Connecting wires are attached using solder, and the whole assembly is dipped into a porous coating material that dries hard and protects the capacitor from damage.

Film Capacitor

An image of a cut away of a capacitor
A photo of a green capacitor.

Film capacitors are frequently found in high-quality audio equipment, such as headphone amplifiers, record players, graphic equalizers, and radio tuners. Their key feature is that the dielectric material is a plastic film, such as polyester or polypropylene.

The metal electrodes of this film capacitor are vacuum-deposited on the surfaces of long strips of plastic film. After the leads are attached, the films are rolled up and dipped into an epoxy that binds the assembly together. Then the completed assembly is dipped in a tough outer coating and marked with its value.

Other types of film capacitors are made by stacking flat layers of metallized plastic film, rather than rolling up layers of film.

Dipped Tantalum Capacitor

A photo of a cutaway of a Dipped Tantalum Capacitor

At the core of this capacitor is a porous pellet of tantalum metal. The pellet is made from tantalum powder and sintered, or compressed at a high temperature, into a dense, spongelike solid.

Just like a kitchen sponge, the resulting pellet has a high surface area per unit volume. The pellet is then anodized, creating an insulating oxide layer with an equally high surface area. This process packs a lot of capacitance into a compact device, using spongelike geometry rather than the stacked or rolled layers that most other capacitors use.

The device’s positive terminal, or anode, is connected directly to the tantalum metal. The negative terminal, or cathode, is formed by a thin layer of conductive manganese dioxide coating the pellet.

Axial Inductor

An image of a cutaway of a Axial Inductor
A photo of a collection of cut wires

Inductors are fundamental electronic components that store energy in the form of a magnetic field. They’re used, for example, in some types of power supplies to convert between voltages by alternately storing and releasing energy. This energy-efficient design helps maximize the battery life of cellphones and other portable electronics.

Inductors typically consist of a coil of insulated wire wrapped around a core of magnetic material like iron or ferrite, a ceramic filled with iron oxide. Current flowing around the core produces a magnetic field that acts as a sort of flywheel for current, smoothing out changes in the current as it flows through the inductor.

This axial inductor has a number of turns of varnished copper wire wrapped around a ferrite form and soldered to copper leads on its two ends. It has several layers of protection: a clear varnish over the windings, a light-green coating around the solder joints, and a striking green outer coating to protect the whole component and provide a surface for the colorful stripes that indicate its inductance value.

Power Supply Transformer

A photo of a collection of cut wires
A photo of a yellow element on a circuit board.

This transformer has multiple sets of windings and is used in a power supply to create multiple output AC voltages from a single AC input such as a wall outlet.

The small wires nearer the center are “high impedance” turns of magnet wire. These windings carry a higher voltage but a lower current. They’re protected by several layers of tape, a copper-foil electrostatic shield, and more tape.

The outer “low impedance” windings are made with thicker insulated wire and fewer turns. They handle a lower voltage but a higher current.

All of the windings are wrapped around a black plastic bobbin. Two pieces of ferrite ceramic are bonded together to form the magnetic core at the heart of the transformer.

This article appears in the February 2023 print issue.

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