Hollow Microneedle Array Research Articles

Leaf-Face Dendrobium Classifier Based on an Integrated Electrochemical Tongue and Machine Learning.

Botanical sourcing seriously impacts the safety and potency of herbal medicines, restricting the development of the traditional Chinese medicinal industry. Rapid and convenient identification of plant resources is important to address this problem. Herein, we innovated a portable, intelligent, and integrated platform, termed the Smart Electronic Tongue (SET), for right recognizing Dendrobium bonsai of different subspecies and origins. The device is miniaturized with a hollow microneedle array for leaf-face extraction, a press-pumping pipeline for on-demand sample sap suction, plus a five-electrode chip for electrochemical readout. Differential pulse voltammograms on three simplexes of self-assembled monolayers as well as their multiplexed configurations are specialized to generate high-dimensional fingerprinting of Dendrobium subtypes. Taking advantage of machine learning algorithms, the platform achieves automatic authentication over eight varieties with a discriminatory accuracy of 95%. Given this, we anticipate that such a bionic sensing setup would offer a versatile solution toward the classification of diverse officinals at the point of need.

Integrated 3D-Printed Hollow Microneedle Array and Lateral Flow Immunoassay for Point-of-Care Wound Healing Monitoring.

Chronic wound management requires continuous monitoring to assess healing and guide treatment. We developed a hollow microneedle array patch integrated with a lateral flow immunoassay strip to address the need for convenient, home-based diagnostics. This device extracts wound exudate directly from the wound matrix, overcoming the limitations of conventional swab sampling, which relies on surface exudate collection. The patch provides a minimally invasive, rapid solution to assess the wound healing phase. The immunoassay delivers a colorimetric signal visible to the naked eye, facilitating straightforward interpretation by clinicians within 10 min. In a clinical study involving 90 patients, matrix metalloproteinase 8 (MMP-8) was identified as a critical biomarker, achieving 80.3% sensitivity in detecting the proliferative phase. A specific lateral flow immunoassay for MMP-8 was developed with a detection limit of 0.7 ng/mL, lower than the threshold level for the proliferative healing phase (164.7 ng/mL). The hollow microneedle array patch was 3D-printed for cost-efficiency (less than €0.10 per patch) with a height of 865 ± 6 μm, allowing for a painless, easy sampling. Mechanical tests confirmed the durability of the patch, while cytotoxicity assays demonstrated its biocompatibility. Prevalidation using an ex vivo skin model showed the patch could extract 61 ± 6 μL of exudate, with a 122% recovery rate for MMP-8 detection, highlighting its efficiency in biomarker extraction. This approach represents a significant advance in decentralized wound care, offering a low-cost, user-friendly tool for at-home monitoring of chronic wounds, potentially improving early intervention and reducing hospital visits.

Development of an osmosis-assisted hollow microneedle array integrated with dual-functional electrochemical sensor for urea and pH monitoring in interstitial fluid

In healthcare, accurate detection of biomarkers is paramount for disease diagnosis, prevention, and personal health surveillance. This study focused on developing and validating a MgCl2 deposited hollow microneedle array integrated with a dual-functional sensor system, which was used for osmosis-assisted boosted interstitial fluid extraction, the simultaneous and continuous monitoring of urea and pH in interstitial fluid. The urea sensor component was fabricated by electro-depositing prussian blue onto a carbon electrode, followed by applying a molecularly imprinted polymer layer, ensuring high specificity and sensitivity. The pH sensor was constructed through electropolymerization of polyaniline, exhibiting a linear response across a wide pH range. When tested in artificial skin matrix, the system demonstrated excellent in vitro electrochemical sensing performance with high linearity and repeatability. At the same time, the practical in vivo sensing performance of the system was verified in Sprague-Dawley (SD) rats. The development of the system underscores its potential as a valuable tool for continuous health monitoring.

3D‐Printed Hollow Microneedles Array with Luer Lock Connection for Facile and Painless Intradermal Injection: A Proof of Concept

AbstractA 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography.

Integration of Hollow Microneedle Arrays with Jellyfish-Shaped Electrochemical Sensor for the Detection of Biomarkers in Interstitial Fluid

This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.

Design and characterization of 3D-printed hollow microneedle arrays for transdermal insulin delivery

The delivery of insulin to diabetic patients remains a challenge due to the limitations of current insulin delivery paradigms, including painful cannula insertion, potential infections, interference with activity, embarrassment, and sometimes cost. To address this problem, we designed and fabricated nine prototypes of stereolithographic 3D-printed microneedle arrays (MNAs) appropriate for the minimally invasive delivery of insulin. We characterized their transdermal penetration performance by delivering fluid at a constant rate to porcine skin through these MNAs. Moreover, we characterized the force required for these MNAs to puncture porcine skin using a mechanical testing apparatus. We developed an improved method of mechanical testing for the MNAs against porcine skin by incorporating an imitation soft tissue layer under the skin and compared the MNA results with those using a single microneedle and a hypodermic needle. In addition, we investigated the mechanical flexural strength of the MNAs by performing a flexural failure load test on them. We confirmed that the prototype MNAs are mechanically robust and do not fracture during skin penetration, setting the stage for future trials in vitro and in vivo. The final, optimized designs are freely available in stereolithography (STL) file format.

Enhanced Interstitial Fluid Extraction and Rapid Analysis via Vacuum Tube-Integrated Microneedle Array Device.

Advancing the development of point-of-care testing (POCT) sensors that utilize interstitial fluid (ISF) presents considerable obstacles in terms of rapid sampling and analysis. Herein, an innovative strategy is introduced that involves the use of a 3D-printed, hollow microneedle array patch (MAP), in tandem with a vacuum tube (VT) connected through a hose, to improve ISF extraction efficiency and facilitate expedited analysis. The employment of negative pressure by the VT allows the MAP device to effectively gather ≈18µL of ISF from the dermis of a live rabbit ear within a concise period of 5min. This methodology enables the immediate and minimally invasive measurement of glucose levels within the body, employing personal healthcare meters for quantification. The fusion of the VT and MAP technologies provides for their effortless integration into a comprehensive and mobile system for ISF analysis, accomplished by preloading the hose with custom sensing papers designed to detect specific analytes. Moreover, the design and functionality of this integrated VT-MAP system are intuitively user-friendly, eliminating the requirement for specialized medical expertise. This feature enhances its potential to make a significant impact on the field of decentralized personal healthcare.

A 3D-printed hollow microneedle-based electrochemical sensing device for in situ plant health monitoring

Plant health monitoring is devised as a new concept to elucidate in situ physiological processes. The need for increased food production to nourish the growing global population is inconsistent with the dramatic impact of climate change, which hinders crop health and exacerbates plant stress. In this context, wearable sensors play a crucial role in assessing plant stress. Herein, we present a low-cost 3D-printed hollow microneedle array (HMA) patch as a sampling device coupled with biosensors based on screen-printing technology, leading to affordable analysis of biomarkers in the plant fluid of a leaf. First, a refinement of the 3D-printing method showed a tip diameter of 25.9 ± 3.7 μm with a side hole diameter on the microneedle of 228.2 ± 18.6 μm using an affordable 3D printer (<500 EUR). Notably, the HMA patch withstanded the forces exerted by thumb pressing (i.e. 20-40 N). Subsequently, the holes of the HMA enabled the fluid extraction tested in vitro and in vivo in plant leaves (i.e. 13.5 ± 1.1 μL). A paper-based sampling strategy adapted to the HMA allowed the collection of plant fluid. Finally, integrating the sampling device onto biosensors facilitated the in situ electrochemical analysis of plant health biomarkers (i.e. H2O2, glucose, and pH) and the electrochemical profiling of plants in five plant species. Overall, this electrochemical platform advances precise and versatile sensors for plant health monitoring. The wearable device can potentially improve precision farming practices, addressing the critical need for sustainable and resilient agriculture in changing environmental conditions.

GEOMETRIC DETERMINANTS OF CELL VIABILITY FOR 3D-PRINTED HOLLOW MICRONEEDLE ARRAY-MEDIATED DELIVERY.

A wide range of emerging biomedical applications and clinical interventions rely on the ability to deliver living cells via hollow, high-aspect-ratio microneedles. Recently, microneedle arrays (MNA) have gained increasing interest due to inherent benefits for drug delivery; however, studies exploring the potential to harness such advantages for cell delivery have been impeded due to the difficulties in manufacturing high-aspect-ratio MNAs suitable for delivering mammalian cells. To bypass these challenges, here we leverage and extend our previously reported hybrid additive manufacturing (or "three-dimensional (3D) printing) strategy-i.e., the combined the "Vat Photopolymerization (VPP)" technique, "Liquid Crystal Display (LCD)" 3D printing with "Two-Photon Direct Laser Writing (DLW)"-to 3D print hollow MNAs that are suitable for cell delivery investigations. Specifically, we 3D printed four sets of 650 μm-tall MNAs corresponding to needle-specific inner diameters (IDs) of 25 μm, 50 μm, 75 μm, and 100 μm, and then examined the effects of these MNAs on the post-delivery viability of both dendritic cells (DCs) and HEK293 cells. Experimental results revealed that the 25 μm-ID case led to a statistically significant reduction in post-MNA-delivery cell viability for both cell types; however, MNAs with needle-specific IDs ≥ 50 μm were statistically indistinguishable from one another as well as conventional 32G single needles, thereby providing an important benchmark for MNA-mediated cell delivery.

Bioinspired labrum-shaped stereolithography (SLA) assisted 3D printed hollow microneedles (HMNs) for effectual delivery of ceftriaxone sodium

Microneedles (MNs), a microsystem having needle height in micrometers, have gained significant attention due to their minimum invasiveness, painless, and easy-to-administer nature. Here, we introduce a hollow microneedle (HMNs) array with bio-inspired labrum tip for low insertion force and desired mechanical strength, fabricated using vat-photopolymerization mediated stereolithography (SLA) assisted 3D printing technology utilizing biocompatible photo-crosslinkable and curable resin as feedstock. Fabricated HMNs was used for the effective transdermal delivery of a broad-spectrum antibiotics i.e., ceftriaxone sodium (CEF) with a high molecular weight of 554.58 g mol−1, possessing gastro-intestinal (GI) instability and low oral bioavailability (BA). The bio-inspired labrum tip structure of the fabricated HMNs was evaluated by digital microscopy and scanning electron microscopy (SEM) to ensure the printed prototype's superiority in terms of dimensions and array uniformity. The HMN microchannels were then characterized by X-ray microcomputer tomography (µCT) to ascertain the quality of internal channels and ensure even distribution of drug solution. Further, HMNs was also characterized for mechanical and penetration analysis. Suggesting a low force of 1.54 N was required for its effective penetration with a sufficient fracture force of around 171.82 N. The ex vivo skin permeation profile of CEF from the HMNs revealed 100 ± 0.80 % CEF permeation through porcine skin within 18 hr. Finally, a pre-clinical efficacy assessment of CEF-reservoir HMNs was performed in an experimental animal model, revealing efficient penetrability and desired BA of CEF. Overall results demonstrated the active transdermal drug delivery potential of these fabricated bio-inspired HMNs as a unique device for customized and personalized treatment.

Wearable Microneedle-Based Array Patches for Continuous Electrochemical Monitoring and Drug Delivery: Toward a Closed-Loop System for Methotrexate Treatment.

Wearable devices based on microneedle (MN) technology have recently emerged as tools for in situ transdermal sensing or delivery in interstitial fluid (ISF). Particularly, MN-based electrochemical sensors allow the continuous monitoring of analytes in a minimally invasive manner through ISF. Exogenous small molecules found in ISF such as therapeutic drugs are ideal candidates for MN sensors due to their correlation with blood levels and their relevance for the optimal management of personalized therapies. Herein, a hollow MN array patch is modified with conductive pastes and functionalized with cross-linked chitosan to develop an MN-based voltammetric sensor for continuous monitoring of methotrexate (MTX). Interestingly, the chitosan coating avoids biofouling while enabling the adsorption of MTX at the electrode's surface for sensitive analysis. The MN sensor exhibits excellent analytical performance in vitro with protein-enriched artificial ISF and ex vivo under a Franz diffusion cell configuration. The MN sensor shows a linear range from 25 to 400 μM, which fits within the therapeutic range of high-dose MTX treatment for cancer patients and an excellent continuous operation for more than two days. Moreover, an iontophoretic hollow MN array patch is developed with the integration of both the anode and cathode in the single MN array patch. The ex vivo characterization demonstrates the transdermal on-demand drug delivery of MTX. Overall, the combination of both MN patches represents impactful progress in closed-loop systems for therapeutic drug management in disorders such as cancer, rheumatoid arthritis, or psoriasis.

Microfluidic-based plasmonic microneedle biosensor for uric acid ultrasensitive monitoring

Uric acid (UA) is considered a potential risk factor in the causation or progression of kidney disease. Capabilities in personalized health monitoring enabled by capture and quantitative analysis of uric acid in the interstitial fluid could make up for the limitations of approach assessment of blood samples. Herein, we report a microfluidic−based wearable plasmonic microneedle sensor for interstitial fluid (ISF) sampling and minimally invasive uric acid monitoring. Under the force of the negative pressure generated by finger push. The hollow microneedle array could extract and deliver subcutaneous fluids to the sensing chamber by a microfluidic channel for SERS detection. The SERS sensing chip based on three-dimensional (3D) gold nanoarrays was found to have excellent reproducibility with 5.96% RSD. This high−density microarray showed ultrasensitive and label-free detection of uric acid molecules with a detection limit of 0.51 µM and enable fast identification of target molecules by integration with a handheld Raman spectrometer. The sensing platform may help bring unlimited possibilities for efficient medical healthcare and early disease prevention in daily life.

Microneedle array-based electrochemical sensor functionalized with SWCNTs for the highly sensitive monitoring of MDMA in interstitial fluid

Illicit drug consumption constitutes a great concern worldwide due to its increased spread and abuse, and the negative consequences exerted on society. For instance, 3,4-methylenedioxymethamphetamine (MDMA), a synthetic amphetamine-type substance, was abused by 20 million people worldwide in 2020. This psychoactive substance exerts a myriad of effects on the human body being dangerous for the consumer’s health. Besides, MDMA has been used in the treatment of some psychiatric conditions. Therefore, the development of wearable devices for MDMA sensing in biological fluids is of great importance for forensic toxicology (e.g., monitoring of patients with suspected or known MDMA consumption) as well as for therapeutic management of patients. Herein, we report the development of a wearable electrochemical platform based on a hollow microneedle (MN) array sensor for the monitoring of MDMA in the interstitial fluid by square-wave voltammetry. First, the holes of the MN array were modified with conductive pastes to devise a MN patch with a three-electrode system. Subsequently, the functionalization of the working electrode with nanomaterials enhanced MDMA detection. Thereafter, analytical parameters were evaluated exhibiting a slope of 0.05 µA µM−1 within a linear range from 1 to 50 µM and a limit of detection of 0.75 µM in artificial interstitial fluid. Importantly, critical parameters such as selectivity, piercing capability, temperature, reversibility and stability were assessed. Overall, the obtained MN sensor exhibited excellent analytical performance, making it a promising tool for MDMA tracking in interstitial fluid for individuals on probation or under therapeutic treatment.

Soft microfiber-based hollow microneedle array for stretchable microfluidic biosensing patch with negative pressure-driven sampling

Wearable point-of-care testing devices are essential for personalized and decentralized healthcare. They can collect biofluid samples from the human body and use an analyzer to detect biomolecules. However, creating an integrated system is challenging due to the difficulty of achieving conformality to the human body, regulating the collection and transport of biofluids, developing a biosensor patch capable of precise biomolecule detection, and establishing a simple operation protocol that requires minimal wearer attention. In this study, we propose using a hollow microneedle (HMN) based on soft hollow microfibers and a microneedle-integrated microfluidic biosensor patch (MIMBP) capable of integrated blood sampling and electrochemical biosensing of biomolecules. The soft MIMBP includes a stretchable microfluidic device, a flexible electrochemical biosensor, and a HMN array made from flexible hollow microfibers. The HMNs are fabricated by electroplating flexible and mechanically durable hollow microfibers made from a nanocomposite matrix of polyimide, a poly (vinylidene fluoride-co-trifluoroethylene) copolymer, and single-walled carbon nanotubes. The MIMBP uses the negative pressure generated by a single button push to collect blood and deliver it to a flexible electrochemical biosensor modified with a gold nanostructure and Pt nanoparticles. We have demonstrated that glucose can be accurately measured up to the molar range in whole human blood collected through the microneedle. The MIMBP platform with HMNs has great potential as a foundation for the future development of simple, wearable, self-testing systems for minimally invasive biomolecule detection. This platform capable of sequential blood collection and high sensitivity glucose detection, which are ideal for personalized and decentralized healthcare.

Design and development of a piezoelectric driven micropump integrated with hollow microneedles for precise insulin delivery

A significant rise in diabetes has spurred researchers to develop more painless, patient-friendly, precise therapeutic products for insulin delivery. There is extensive use of valveless micropumps in numerous medical devices since they constitute the key component in the microsystem for fluid control and precision delivery. This study reports a novel integrated insulin delivery device consisting of a valveless piezoelectric-driven micropump, a hollow microneedle array, and a fluid reservoir. At first, a simple, low-cost micropump driven by a piezoelectric disc is fabricated using 3D printing technology. Nozzle/diffuser elements are used instead of any active valves in order to avoid leakage and other complexities. To investigate the viability of the micropump, an analysis of the vibrational performance of the piezoelectric actuator is performed. COMSOL Multiphysics is used to perform the transient analysis of the piezoelectric actuator of the micropump. Further, simulation-based flow analyses are carried out to verify the outcomes of the experimental studies. The experimental results indicate that the maximum flow rate of the micropump is achieved at 400 Hz for insulin. To realize the final aim of this work, an array of hollow SU-8 microneedles is fabricated and then finally integrated with the piezoelectric-driven valveless micropump and fluid reservoir. This integrated insulin delivery device is tuneable and can achieve a maximum flow rate of 120.5 µl min−1 for insulin at 60Vpp, 400 Hz sine wave.

Cleanroom-Free Fabrication of Microneedles for Multimodal Drug Delivery.

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high-resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low-cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink-molding of hydrogels to form high-resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.

Innovative Fabrication of Hollow Microneedle Arrays Enabling Blood Sampling with a Self-Powered Microfluidic Patch

Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 μm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 μL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.

3D-Printed Microinjection Needle Arrays via a Hybrid DLP-Direct Laser Writing Strategy.

Microinjection protocols are ubiquitous throughout biomedical fields, with hollow microneedle arrays (MNAs) offering distinctive benefits in both research and clinical settings. Unfortunately, manufacturing-associated barriers remain a critical impediment to emerging applications that demand high-density arrays of hollow, high-aspect-ratio microneedles. To address such challenges, here, a hybrid additive manufacturing approach that combines digital light processing (DLP) 3D printing with "ex situ direct laser writing (esDLW)" is presented to enable new classes of MNAs for fluidic microinjections. Experimental results for esDLW-based 3D printing of arrays of high-aspect-ratio microneedles-with 30 μm inner diameters, 50 μm outer diameters, and 550 μm heights, and arrayed with 100 μm needle-to-needle spacing-directly onto DLP-printed capillaries reveal uncompromised fluidic integrity at the MNA-capillary interface during microfluidic cyclic burst-pressure testing for input pressures in excess of 250 kPa (n = 100 cycles). Ex vivo experiments perform using excised mouse brains reveal that the MNAs not only physically withstand penetration into and retraction from brain tissue but also yield effective and distributed microinjection of surrogate fluids and nanoparticle suspensions directly into the brains. In combination, the results suggest that the presented strategy for fabricating high-aspect-ratio, high-density, hollow MNAs could hold unique promise for biomedical microinjection applications.

Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications

The use of computational tools for the development of technologies in fields such as medicine and engineering has facilitated the process of designing new components and devices for these areas. In this work, two proposals focused on a hollow microneedle array (MNA) for the administration of an analgesic drug are shown and evaluated by means of a computational fluid dynamics (CFD) simulation distributed in three stages. In the first stage, the behavior of lidocaine through the MNA was evaluated as a workflow. Then, the possible entry of the drug into the organism, which was established as a porous aqueous medium, was modeled. Finally, a joint simulation was performed to understand the general behavior in the interaction between the outflow of an MNA and the body to which lidocaine is administered. The input parameters to the simulation were set at a velocity of 0.05 m∙s-1, at a pressure of 2000 Pa, the dominant behavior was defined as laminar flow, and a resistive pressure at the inlet of 400 Pa. Our results indicate that the vertical flow exhibits a better fluid distribution across the MNAs and favorable infiltration behavior, representing better delivery of the analgesic to the skin capillaries.

Transdermal on-demand drug delivery based on an iontophoretic hollow microneedle array system.

Transdermal drug delivery has emerged as an alternative administration route for therapeutic drugs, overcoming current issues in oral and parenteral administration. However, this technology is hindered by the low permeability of the stratum corneum of the skin. In this work, we develop a synergic combination of two enhancing technologies to contribute to an improved and on-demand drug delivery through an iontophoretic system coupled with hollow microneedles (HMNs). For the first time, a polymeric HMN array coupled with integrated iontophoresis for the delivery of charged molecules and macromolecules (e.g. proteins) is devised. To prove the concept, methylene blue, fluorescein sodium, lidocaine hydrochloride, and bovine serum albumin-fluorescein isothiocyanate conjugate (BSA-FITC) were first tested in an in vitro setup using 1.5% agarose gel model. Subsequently, the ex vivo drug permeation study using a Franz diffusion cell was conducted, exhibiting a 61-fold, 43-fold, 54-fold, and 17-fold increment of the permeation of methylene blue, fluorescein sodium, lidocaine hydrochloride, and BSA-FITC, respectively, during the application of 1 mA cm-2 current for 6 h. Moreover, the total amount of drug delivered (i.e. in the skin and receptor compartment) was analysed to untangle the different delivery profiles according to the types of molecule. Finally, the integration of the anode and cathode into an iontophoretic hollow microneedle array system (IHMAS) offers the full miniaturisation of the concept. Overall, the IHMAS device provides a versatile wearable technology for transdermal on-demand drug delivery that can improve the administration of personalised doses, and potentially enhance precision medicine.