The sensor could help patients stay above the

image: A tiny touch sensor uses sweat to detect the level of lithium in the body.
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Credit: Jialun Zhu and Shuyu Lin

CHICAGO, Aug. 21, 2022 — Lithium can ease symptoms of bipolar disorder and depression — if taken in the right amount. Too little won’t work, while too much can lead to dangerous side effects. To accurately monitor the amount of this drug in the body, patients must undergo invasive blood tests. But today, scientists are reporting the invention of a tiny sensor that detects lithium levels in sweat on the surface of a finger in as little as 30 seconds, without a trip to the clinic.

The researchers will present their results today at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid meeting held virtually and in-person August 21-25, with on-demand access available August 26-September 26. 9. The meeting includes almost 11,000 presentations on a wide range of scientific topics.

Not only does lithium have to be taken in a certain dose, but patients often have trouble taking it as prescribed and may miss pills. So when the medication seems not to be working, health care providers need to know how much of the medication the patient is actually swallowing. But current monitoring options have significant drawbacks. For example, blood tests produce accurate results, but they are invasive and time-consuming. Pill counters, on the other hand, do not directly measure medication intake. To address these limitations, the team turned to another bodily fluid.

“Although it is not visible, the human body constantly produces sweat, often only in very small amounts,” says Shuyu Lin, Ph.D., a postgraduate research student who co-presents the work with the graduate student Jialun Zhu at Encounter. “Small molecules derived from drugs, including lithium, appear in this sweat. We recognized this as an opportunity to develop a new type of sensor that would detect these molecules. »

“With just a touch, our new device can get clinically useful information at the molecular level about what’s circulating in the body,” says Sam Emaminejad, Ph.D., the project’s principal investigator, who works at the University of California. in Los Angeles. (UCLA). “We already interact with many touch-based electronic devices, such as smart phones and keyboards, so this sensor could integrate seamlessly into everyday life.”

Designing a sensor to detect lithium, however, presented some technical challenges. Sweat is usually only present in minute amounts, but the electrochemical sensing needed to detect charged lithium particles required a watery or watery environment. To provide this, the team designed a water-based gel containing glycerol. This additional ingredient prevented the gel from drying out and created a controlled environment for the electronics of the sensor.

To trap the lithium ions after passing through the gel, the team used an ion-selective electrode. The accumulating ions generate an electrical potential difference relative to a reference electrode. The researchers used this difference to infer the concentration of lithium present in sweat. Together, these components include a tiny rectangular sensor smaller than the head of a thumbtack and capable of detecting lithium in about 30 seconds. The sensor is still in preliminary testing, but eventually researchers plan to integrate it into a larger, yet to be designed, system that provides visual feedback to the provider or patient.

After characterizing the sensor using an artificial fingertip, the team recruited real people to test it, including a person on lithium therapy. The researchers recorded this person’s lithium levels before and after taking the drug. They found that these measurements approximated those derived from saliva, which previous research has shown accurately measure lithium levels. In the future, the researchers plan to study the effects of lotion and other skin products on sensor readings.

This technology also has applications beyond lithium. Emaminejad is developing similar touch sensors to monitor alcohol and acetaminophen, a painkiller also known as Tylenol®, while exploring the possibility of detecting other substances. Comprehensive detection systems could include additional features, such as secure fingerprint encryption or, for substances subject to abuse, a robotic dispensing system that releases medication only if the patient has a low level in his blood circulation.

The researchers acknowledge support and funding from the National Science Foundation, Brain and Behavior Foundation, Precise Advanced Technologies and Health Systems for Underserved Populations, and UCLA Henry Samueli School of Engineering and Applied Sciences.

ACS Fall 2022 will be a vaccination-mandated and mask-wearing event recommended for all ACS attendees, exhibitors, vendors, and staff planning to attend in person in Chicago. For detailed information on the requirement and all ACS security measures, please visit the ACS website.

The American Chemical Society (ACS) is a nonprofit organization accredited by the United States Congress. ACS’s mission is to advance the broader chemical enterprise and its practitioners for the benefit of the Earth and all its inhabitants. The Society is a global leader in promoting excellence in science education and access to chemistry-related information and research through its multiple search solutions, peer-reviewed journals, its scientific conferences, e-books and weekly periodicals. Chemistry and Engineering News. ACS journals are among the most cited, trusted and widely read in the scientific literature; however, the ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing global scientific knowledge. ACS’s principal offices are located in Washington, DC, and Columbus, Ohio.

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Note to Editors: Please note that this research was presented at a meeting of the American Chemical Society.

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Title
Noninvasive tactile lithium monitoring using an organohydrogel-based sensing interface

Summary
Lithium salt is one of the most widely used psychiatric drugs for people with bipolar disorder. Due to its narrow therapeutic window (~0.6 – 1.2 mM) and high non-adherence rate (~40%), it should be closely monitored to maximize treatment efficacy. Standard lithium monitoring practices for accurate dosing are confined to centralized hospitals and involve invasive blood sampling and expensive laboratory analysis with a long turnaround time. Additionally, there is currently no direct monitoring of lithium adherence available, and indirect monitoring solutions (e.g. pill counters) are unable to verify the actual (inherently non-specific) ingestion event. .

Overcoming these limitations, here we have developed a touch-based noninvasive lithium monitoring solution for the decentralized management of lithium drug therapy. This solution is based on a hydrogel-coated sensing interface that collects and analyzes (in situ) the flow of circulating lithium molecules that distribute to fingertips. This interface was constructed using a thin organohydrogel-coated lithium ion-selective electrode (TOH-ISE), where the TOH coating was specially designed to stabilize the sensing conditions. In particular, by adopting a water-glycerol bi-solvent matrix, the gel was endowed with an anti-dehydration property (negligible weight loss for >2 weeks storage in an ambient environment), solving the interface dehydration challenge. previously reported hydrogel-based. . Additionally, in the designed interface configuration, the TOH coating serves as a controlled microenvironment to condition the ISE in situ; thus, it minimizes ISE signal drift (a major challenge prohibiting translation of ISEs in real-world applications).

To illustrate the clinical utility of our solution, the developed tactile sensing interface was tested on a patient prescribed with a lithium-based drug, where the rise in circulating drug levels after taking the drug was captured. with success. Together, our preliminary results demonstrate the relevance of our tactile solution for monitoring lithium adherence, and more broadly for managing lithium drug therapy.


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