Microneedle Sensors: The Tiny Revolution in Wearable Diagnostics

Microneedle sensors represent a significant leap forward in the field of wearable diagnostics. These devices, characterized by their minuscule size, typically less than 1 mm in height, are designed to penetrate only the outermost layers of the skin, providing painless access to interstitial fluid (ISF). This fluid, which bathes the cells, contains a wealth of biomarkers that can offer valuable insights into an individual's health status.

Fig.1 Schematic illustration of a smart probe-modified epidermal microneedle sensor patch. (Ben H. H., et al., 2025)

Design and Structure of Microneedle Sensors

Types of Microneedles

Dissolvable Microneedles

Composed of materials that break down upon contact with body fluids, dissolvable microneedles can release sensors or drugs. This type is particularly useful in applications where a slow and controlled release of substances is required. Some formulations of dissolvable microneedles have been used to deliver vaccines, with the microneedles dissolving after administration and releasing the vaccine components into the body.

Solid Microneedles

These are often coated with sensors on their surface. The coating is designed to interact with specific biomarkers present in the ISF. For example, solid microneedles coated with an enzyme sensitive to lactate can detect changes in lactate levels, which can be indicative of physical exertion or certain medical conditions.

Hollow Microneedles

Functioning much like tiny straws, hollow microneedles are capable of extracting interstitial fluid. Their design allows for the collection of a small but sufficient volume of fluid for analysis. For instance, in a study focused on glucose monitoring, hollow microneedles were able to accurately draw ISF, enabling the measurement of glucose levels within the fluid.

Hydrogel-based Microneedles

Made from porous hydrogel materials, these microneedles absorb interstitial fluid. The hydrogel's porous structure allows for efficient fluid uptake, and the absorbed fluid can then be analyzed for various biomarkers.

Sensor Integration

Microneedle sensors integrate advanced detection technologies with the microneedle structure. Electrochemical sensors are commonly used. In an electrochemical glucose sensor, the microneedle is modified to act as a working electrode. When glucose in the ISF comes into contact with the enzyme (such as glucose oxidase) coated on the microneedle, a chemical reaction occurs, producing an electrical current. The magnitude of this current is proportional to the glucose concentration in the fluid.

Other sensor types include fluorescent microneedles, which use light-emitting molecules that change their fluorescence properties when they bind to specific biomarkers; colorimetric microneedles, which change color in the presence of target substances, allowing for visual detection; and potentiometric sensors, which measure voltage changes to detect ions like sodium or potassium.

Applications of Microneedle Sensors in Wearable Diagnostics

Diabetes Management

Continuous glucose monitoring (CGM) is one of the most prominent applications of microneedle sensors. Devices like the Dexcom G6 and Abbott Freestyle Libre 2 have transformed the lives of individuals with diabetes. These CGM systems use microneedle-based sensors to continuously measure glucose levels in the ISF, providing real-time data that can be used to adjust insulin doses and manage blood sugar levels more effectively.

Recent research has also focused on developing multi-parameter sensors for diabetes. For example, a microneedle array has been created that can simultaneously measure glucose and lactate. This is important because lactate levels can provide additional information about the body's metabolic state, helping to better understand how the body is responding to insulin therapy.

Electrolyte Monitoring

Electrolytes such as sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺), and chloride (Cl^-) play crucial roles in maintaining proper bodily functions, including nerve and muscle function, and fluid balance. A microneedle system designed for transdermal electrolyte tracking consists of seven stainless-steel microneedles, each specifically tailored to detect a particular ion. In pre-clinical studies on rat skin, this system accurately measured pH and six different ions, demonstrating its potential for use in monitoring patients with electrolyte imbalances, such as those in intensive care units or athletes during strenuous exercise.

Disease Detection and Biomarker Monitoring

Microneedle sensors are also being explored for the detection of various diseases. In the case of cancer, a microneedle patch has been developed to sense tyrosinase, an enzyme that is overproduced in melanoma. The patch uses a "smart probe" that reacts with tyrosinase, generating an electrical signal that can alert users to the potential presence of the cancer.

For infectious diseases, the integration of CRISPR technology into microneedle sensors has shown great promise. CRISPR-based microneedle sensors can detect specific nucleic acid sequences of viruses, allowing for rapid and accurate diagnosis of viral infections at the point-of-care.

Drug Monitoring

In the area of pharmacology, microneedle sensors can be used to monitor drug levels in the body. For drugs like methotrexate, which is used in the treatment of cancer and rheumatoid arthritis, careful dosing is essential to avoid toxicity. A microneedle sensor has been developed that can measure methotrexate levels through the skin, enabling doctors to adjust drug doses in real-time based on the patient's individual pharmacokinetics.

Advantages of Microneedle Sensors in Wearable Diagnostics

Painless and Non-Invasive

Since microneedles only penetrate the outermost layers of the skin, they avoid reaching nerve endings and blood vessels, making the process virtually painless. This is a significant advantage over traditional blood-drawing methods, which can be uncomfortable and may deter some patients from regular monitoring.

Real-Time and Continuous Monitoring

Microneedle sensors enable real-time and continuous monitoring of biomarkers. This provides a more comprehensive picture of an individual's health status over time, as opposed to intermittent measurements obtained through traditional diagnostic methods. For example, in CGM, continuous data allows patients and healthcare providers to identify trends and patterns in blood sugar levels, facilitating more proactive diabetes management.

High Sensitivity and Specificity

Advanced sensor technologies integrated with microneedles offer high sensitivity and specificity. For instance, CRISPR-based microneedle sensors can detect ultra-trace amounts of nucleic acids, with a sensitivity as low as 0.3 femtomolar. This high sensitivity allows for the early detection of diseases, when biomarker levels may still be very low.

Challenges and Future Outlook

Challenges

Biocompatibility: Some individuals may experience allergic reactions or skin irritations to the materials used in microneedle sensors. Ensuring the use of biocompatible materials, such as natural polymers like chitosan or silk, is crucial to minimize these adverse reactions.
Biofouling: Over time, proteins and other substances in the ISF can accumulate on the sensor surface, a phenomenon known as biofouling. This can interfere with the sensor's ability to accurately detect biomarkers. Developing anti-fouling coatings, such as special polymers that repel proteins, is an area of active research.
Multiplexing: While the ability to detect multiple biomarkers simultaneously (multiplexing) is highly desirable, it presents significant technical challenges. Each biomarker may require a different sensor design, and integrating multiple sensors into a single microneedle array without cross-interference is a complex task.

Future Outlook

The future of microneedle sensors in wearable diagnostics is promising. Research is focused on developing longer-lasting sensors, improving multiplexing capabilities, and reducing costs through mass production techniques such as 3D printing. As these technologies continue to evolve, microneedle sensors are likely to become more widely available, enabling personalized and proactive healthcare for a broader population. In addition, the application of microneedle sensors may expand beyond human health, into areas such as veterinary medicine and agriculture, further enhancing their impact on global well-being.

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Reference

Ben Halima, Hamdi, Boris Lakard, and Nicole Jaffrezic-Renault. "Microneedle-Based Sensors for Wearable Diagnostics." Chemosensors 13.2 (2025): 68.

This article is for research use only. Do not use in any diagnostic or therapeutic application.