Fabrication of Multiple-Channel Electrochemical Microneedle Electrode Array via Separated Functionalization and Assembly Method.

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.

Integrated electronic/fluidic microneedle system for glucose sensing and insulin delivery.

Background: Precise and dynamic blood glucose regulation is paramount for both diagnosing and managing diabetes. Continuous glucose monitoring (CGM) coupled with insulin pumps forms an artificial pancreas, enabling closed-loop control of blood glucose levels. Indeed, this integration necessitates advanced micro-nano fabrication techniques to miniaturize and combine sensing and delivery modules on a single electrode. While microneedle technology can mitigate discomfort, concerns remain regarding infection risk and potential sensitivity limitations due to their short needle length. Methods: This study presents the development of an integrated electronic/fluidic microneedle patch (IEFMN) designed for both glucose sensing and insulin delivery. The use of minimally invasive microneedles mitigates nerve contact and reduces infection risks. The incorporation of wired enzymes addresses the issue of "oxygen deprivation" during glucose detection by decreasing the reliance on oxygen. The glucose-sensing electrodes employ wired enzyme functionalization to achieve lower operating voltages and enhanced resilience to sensor interference. The hollow microneedles' inner channel facilitates precise drug delivery for blood glucose regulation. Results: Our IEFMN-based system demonstrated high sensitivity, selectivity, and a wide response range in glucose detection at relatively low voltages. This effectively reduced interference from both external and internal active substances. The microneedle array ensured painless and minimally invasive skin penetration, while wired enzyme functionalization not only lowered sensing potential but also improved glucose detection accuracy. In vivo, experiments conducted in rats showed that the device could track subcutaneous glucose fluctuations in real-time and deliver insulin to regulate blood glucose levels. Conclusions: Our work suggests that the IEFMN-based system, developed for glucose sensing and insulin delivery, exhibits good performance during in vivo glucose detection and drug delivery. It holds the potential to contribute to real-time, intelligent, and controllable diabetes management.

Personalized Machine Learning-Coupled Nanopillar Triboelectric Pulse Sensor for Cuffless Blood Pressure Continuous Monitoring.

A wearable system that can continuously track the fluctuation of blood pressure (BP) based on pulse signals is highly desirable for the treatments of cardiovascular diseases, yet the sensitivity, reliability, and accuracy remain challenging. Since the correlations of pulse waveforms to BP are highly individualized due to the diversity of the patients' physiological characteristics, wearable sensors based on universal designs and algorithms often fail to derive BP accurately when applied on individual patients. Herein, a wearable triboelectric pulse sensor based on a biomimetic nanopillar layer was developed and coupled with Personalized Machine Learning (ML) to provide accurate and continuous monitoring of BP. Flexible conductive nanopillars as the triboelectric layer were fabricated through soft lithography replication of a cicada wing, which could effectively enhance the sensor's output performance to detect weak signal characteristics of pulse waveform for BP derivation. The sensors were coupled with a personalized Partial Least-Squares Regression (PLSR) ML to derive unknown BP based on individual pulse characteristics with reasonable accuracy, avoiding the issue of individual variability that was encountered by General PLSR ML or formula algorithms. The cuffless and intelligent design endow this ML-sensor as a highly promising platform for the care and treatments of hypertensive patients.

3D-assembled microneedle ion sensor-based wearable system for the transdermal monitoring of physiological ion fluctuations.

Monitoring human health is of considerable significance in biomedicine. In particular, the ion concentrations in blood are important reference indicators related to many diseases. Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature. In this study, we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays. The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining; the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided. The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca2+, K+, and Na+ concentrations, and it exhibited good detection performance. The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca2+, K+, and Na+ in the interstitial fluids of rats in real time. By using an integrated circuit design, we constructed the proposed microneedle sensor into a wearable integrated monitoring system. The integrated system could potentially provide information feedback for diseases related to physiological ion changes.

Determination of Transdermal Rate of Metallic Microneedle Array through an Impedance Measurements-Based Numerical Check Screening Algorithm.

Microneedle systems have been widely used in health monitoring, painless drug delivery, and medical cosmetology. Although many studies on microneedle materials, structures, and applications have been conducted, the applications of microneedles often suffered from issues of inconsistent penetration rates due to the complication of skin-microneedle interface. In this study, we demonstrated a methodology of determination of transdermal rate of metallic microneedle array through impedance measurements-based numerical check screening algorithm. Metallic sheet microneedle array sensors with different sizes were fabricated to evaluate different transdermal rates. In vitro sensing of hydrogen peroxide confirmed the effect of transdermal rate on the sensing outcomes. An FEM simulation model of a microneedle array revealed the monotonous relation between the transdermal state and test current. Accordingly, two methods were primely derived to calculate the transdermal rate from the test current. First, an exact logic method provided the number of unpenetrated tips per sheet, but it required more rigorous testing results. Second, a fuzzy logic method provided an approximate transdermal rate on adjacent areas, being more applicable and robust to errors. Real-time transdermal rate estimation may be essential for improving the performance of microneedle systems, and this study provides various fundaments toward that goal.