Colin Dalton

Microneedles have emerged as a versatile technology for biosensing across biomedical domains and are increasingly being explored for other applications like agriculture. This review highlights recent advancements in the development of microneedle-based biosensors in novel areas. Biomedical applications include continuous glucose monitoring, multiplexed biomarker detection beyond glucose, and numerous recent works presenting fully integrated systems comprising microneedle arrays alongside miniaturized wearable electronics. Agricultural applications largely focus on the detection of plant growth markers, hormones, and nutrient levels. Despite significant progress, challenges remain in overcoming biofouling and electrode degradation, optimizing electrode longevity for long-term (weeks to months) in situ monitoring, and creating scalable sensor fabrication processes. Additionally, there is a need for standardized mechanical and electrical testing protocols, and guidelines specifying critical performance metrics that should be reported to facilitate accurate literature comparisons. The review concludes by outlining key opportunities for future research to address these persisting challenges.

This work reports a rapid, cleanroom-free route for fabricating three-electrode microneedle electrochemical biosensors by repurposing the high speed wire bonding technique from the semiconductor industry. The 50 µm diameter Au, Pt, and 30 µm Ag wires were bonded to commercial printed circuit boards (PCBs) to produce freestanding microneedles (MNs) that served as working (WE), counter (CE), and reference (RE) electrodes. Ag MNs were galvanostatically chlorinated to form Ag/AgCl reference electrodes with low drift, −3 ± 0.3 mV over 24 h in phosphate-buffered saline. Au MNs were coated with PEDOT:PSS/glucose oxidase for amperometric glucose sensing from 5–25 mM (sensitivity = 0.37 µA mM-1, +0.50 V working voltage), covering the physiologic range for diabetes management. Platform versatility was demonstrated by nanomolar-range detection after the addition of an aptamer self-assembled monolayer on wire bonded Au MNs. This fully automated, additive wire bonding process provides submillimetre electrode spacing, < US$2 materials cost per trielectrode array, and seamless integration with external sensing hardware for wearable applications owing to the PCB-substrate based approach. We demonstrate a scalable pathway toward multiplexed MN patches for continuous interstitial fluid monitoring and other microneedle-based minimally invasive biosensing applications.

Microneedles are a promising technology for pain-free and efficient pharmaceutical delivery. However, their clinical translation is currently limited by the absence of standardized testing methods for critical quality attributes (CQAs), such as mechanical robustness, which are essential for demonstrating safety and efficacy during regulatory review. A key aspect of mechanical robustness is transverse load capacity, which is currently assessed using diverse, non-standardized methods, which have limited capability to measure transverse failure forces at different heights along a microneedle. This is critical for understanding mechanics of potential failure modes during insertion after skin penetration. In this work we utilize a wire bond shear tester, a piece of test equipment widely used in the semiconductor industry, to measure the transverse load capacities of various microneedle designs. This approach is compatible with diverse microneedle types, geometries, and materials, and offers high-throughput and automated testing capabilities with high precision. We measure transverse failure loads with micron-scale control over the test height and have established comprehensive profiles of mechanical robustness along the length of different microneedle designs, which is a capability not previously demonstrated in literature for polymeric and metal microneedles. Transverse failure forces were 10 ± 0.3 gf–128 ± 12 gf for wire bonded gold and silver microneedles, 11 ± 0.7 gf–480 ± 69 gf for conical and pyramidal polymeric microneedles, and 206 ± 80 gf–381 ± 1 gf for 3D printed conical stainless steel microneedles. Additionally, we present standardized definitions for microneedle structural failure modes resulting from transverse loads, which can facilitate root cause failure analysis and defect detection during design and manufacturing, and aid in risk assessment of microneedle products. This work establishes a standardized approach to evaluating a significant CQA of microneedle products, which is a critical step towards expediting their clinical adoption.

Femtosecond laser material processing (FLMP) was used to make an X-ray mask in a 500 µm thick tungsten sheet without the use of any chemical etch methods. The laser produced an 800 nm wavelength at a 1 kHz repetition rate and a pulse width of 100 fs. The laser beam arrival at the tungsten sheet was synchronized to a computer numerically controlled (CNC) stage that allowed for motion in the XYZθ directions. The X-ray mask design was made using CAD/CAM software (Alphacam 2019 R1) and it consisted of linear, circular, and 45° angle features that covered an area of 10 mm × 10 mm. A total of 70 laser beam passes at a moderate laser energy of 605.94 J/cm² were used to make through-cut features into the tungsten sheet. The morphology of the top view (laser incident, LS) images showed cleaner and smoother cut edges relative to the bottom view (laser exit, LE) images. It was found that the size dimensions of the through-cut features on the LE surfaces were better aligned with the CAD dimensions than those of the LS surfaces. The focused laser beam produced inclined cut surfaces as the beam made the through cut from the LS to the LE of the tungsten sheet. The circular features at the LS surface deviated toward being oval-like on the LE surface, which could be compensated for in future CAD designs. The dependence of the CNC processing speed on the thickness of the etch depth was determined to have a third-order exponential decay relationship, thereby producing a theoretical model that will be useful for future investigators to predict the required experimental parameters needed to achieve a known etch depth in tungsten. This is the first study that has demonstrated the capability of using a femtosecond laser to machine through-cut an X-ray mask in a 500 µm thick tungsten sheet with no involvement of a wet etch or any other such supporting process.

Electrothermal micropumps apply an AC electric field to a conductive fluid within the range of 10 kHz–1 MHz to generate fluid flow. In this frequency range, coulombic forces dominate fluid interactions over opposing dielectric forces, resulting in high flow rates (~50–100 μm/s). To date, the electrothermal effect—using asymmetrical electrodes—has been tested only with single-phase and 2-phase actuation, while dielectrophoretic micropumps have shown improved flow rates with 3- and 4-phase actuation. Simulating muti-phase signals in COMSOL Multiphysics requires additional modules and a more involved implementation to accurately represent the electrothermal effect in a micropump. Here, we report detailed simulations of the electrothermal effect under multi-phase conditions, including single-phase, 2-phase, 3-phase and 4-phase actuation patterns. These computational models indicate that 2-phase actuation leads to the highest flow rate, with 3-phase resulting in a 5% reduced flow rate and 4-phase resulting in an 11% reduced flow rate compared to 2-phase. With these modifications to the simulation, various actuation patterns can later be tested in COMSOL for a range of electrokinetic techniques.

The purpose of this work is to demonstrate the fabrication process for cleanroom-free solid metal microneedles and perform quantification of insertion profiles. Metal microneedles were created using a modified wirebonding process and inserted into porcine tissue to determine design efficacy. Microneedle arrays were analyzed through optical imaging and scanning electron microscopy. Insertion forces were measured using combined uniaxial load cell and resistance measurement data. Microneedle arrays were successfully inserted into porcine tissue with high repeatability and reliability. These arrays demonstrate lower or equivalent insertion forces (less than 3 N) to other forms of microneedles in the literature without the need for complex cleanroom fabrication processes. The microneedle fabrication method presented here rapidly produces mass manufacturable, high-quality microneedle arrays with minimal insertion forces, able to reliably penetrate tissue samples. The manufacturing method presented here achieved array densities as high as 3200 needles cm⁻². These microneedle arrays demonstrate simple fabrication of a reliable, high-density, pain-free drug delivery system, with potential applications in biosensing and electric field modulated drug delivery.

In this editorial note, we briefly review the major findings of the 10 articles published in the Special Issue on microelectrode arrays and application to medical devices

Alternating Current Electrothermal (ACET) micropumps are a well-documented flow induction and mixing method. This phenomenon has significant promise as a reliable microfluidic pumping method for high conductivity biofluids, such as cerebrospinal fluid, urine, or blood. Practical implementations so far have been limited by complex designs focused on maximized flow rates, typically in only one direction at a time. This paper describes a device geometry demonstrating, and quantifying for the first time, fully reversible flow, that is, going from 100% flow in one direction to fully symmetrical 100% flow in the opposite direction. This design incorporates multiple features targeted at practical fabrication and applications. The design enables fine-tuning of flow speeds via adjustable signal strengths in a unique manner compared to traditional ACET devices. A full numerical simulation of this device has been performed within this work. Additionally, this paper reports several methods for increasing usability of ACET devices, including proposing coatings to prevent electrolysis and increase flow rates without the risk of fluid reactions, manufacturing methods for ease of handling, and specific device parameters for implementation in microdevices. The development of an ACET device that can precisely and efficiently pump and extract fluids allows for new applications in integrated biological systems and monitoring devices.

The electrothermal effect has been investigated extensively in microfluidics since the 1990s and has been suggested as a promising technique for fluid manipulations in lab-on-a-chip devices. The purpose of this article is to provide a timely overview of the previous works conducted in the AC electrothermal field to provide a comprehensive reference for researchers new to this field. First, electrokinetic phenomena are briefly introduced to show where the electrothermal effect stands, comparatively, versus other mechanisms. Then, recent advances in the electrothermal field are reviewed from different aspects and categorized to provide a better insight into the current state of the literature. Results and achievements of different studies are compared, and recommendations are made to help researchers weigh their options and decide on proper configuration and parameters.