Needle Array Research Articles

In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity

Objective.Optogenetics allows the manipulation of neural circuitsin vivowith high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models).Approach.Here, we have developed, optimised, and testedin vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181μLEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies.Main results.Thinning the combinedμLED and needle backplane of the device from 300μm to 230μm improved the efficiency of light delivery to tissue by 80%, allowing lowerμLED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1 °C. The device was testedin vivoin the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons.Significance.It was shown that the UOA produced the strongest optogenetic response in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling-demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential activity.

Designing Microneedle Patch for Prophylaxis of Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, which often occurs within 30 postoperative days, especially peaking at 2-3 days. Antiarrhythmic medications such as amiodarone are recommended in clinical practice for the prophylaxis and treatment of POAF. However, conventional oral administration is hindered due to delayed drug action and high risks of systemic toxicity, and emerging localized delivery strategies suffer from a limited release duration (less than 30 days). Herein, we develop a microneedle (MN) patch for localized delivery of amiodarone to the atria in a "First Rapid and Then Sustained" dual-release mode. Specifically, this patch is composed of a needle array integrated with an amiodarone-loaded reservoir for a sustained and steady release for over 30 days; and an amiodarone-containing coating film deposited on the needle surface via the Langmuir-Blodgett technique for a rapid release at the first day. Upon this design, only one MN patch enables a higher drug accumulation in the atrial tissue at the first day than oral administration and simultaneously remains therapeutical levels for over 30 days, despite at a significantly reduced drug dosage (5.08 mg in total versus ∼10 mg per day), thereby achieving ideal preventive effects and safety in a rat model. Our findings indicate that this MN device provides a robust and efficient delivery platform for long-term prophylaxis of POAF.

Hydrothermal self-assembly of needle and sheet spherical array CuCo2O4 nanostructures on graphene aerogels for oxygen evolution reaction

Hydrothermal self-assembly of needle and sheet spherical array CuCo2O4 nanostructures on graphene aerogels for oxygen evolution reaction

In Situ Hydroxide Growth over Nickel-Iron Phosphide with Enhanced Overall Water Splitting Performances.

In this work, three dimensional (3D) self-supported Ni-FeOH@Ni-FeP needle arrays with core-shell heterojunction structure are fabricated via in situ hydroxide growth over Ni-FeP surface. The as-prepared electrodes show an outstanding oxygen evolution reaction (OER) performance, only requiring the low overpotential of 232mV to reach 200mAcm-2 with the Tafel slop of 40mVdec-1. For overall water splitting, an alkaline electrolyzer with these electrodes only requires a cell voltage of 2.14V to reach 1Acm-2. Mechanistic investigations for such excellent electrocatalytic performances are utilized by in situ Raman spectroscopy in conjunction with density functional theory (DFT) calculations. The computation results present that Ni-FeOH@Ni-FeP attains better intrinsic conductivity and the D-band center (close to that of the ideal catalyst), thus giving superior excellent catalytic performances. Likewise, the surface Ni-FeOH layer can improve the structural stability of Ni-FeP cores and attenuate the eventual formation of irreversible FeOOH products. More importantly, the appearance of FeOOH intermediates can effectively decrease the energy barrier of NiOOH intermediates, and then rapidly accelerate the sluggish reaction dynamics, as well as further enhance the electrocatalytic activities, reversibility and cycling stability.

Parametric investigation of wire-EDM parameters for micro channel as a foundation of high-quality micro needle array fabrication

Micro channels are widely used in microfluidics, and medical science for the extraction of DNA, electrophoresis, and blood protein analysis. In the current work, the wire electrical discharge machining (WEDM) process was used to fabricate micro channels on the stainless steel 316 (SS316) substrate. To check the feasibility of fabricating high-quality micro channels and thereafter micro-scale structures with the WEDM process the effect of different process parameters such as pulse-off time, pulse-on time, servo gap reference voltage and wire feed rate were investigated. The quality attributes taken were namely surface roughness of the channel base, overcut, micro channel depth, and material removal rate (MRR). The pulse-on time significantly affects surface roughness and MRR. The servo gap reference voltage is the key process parameter affecting the overcut and micro channel depth. It was observed from the parametric study that 15 µs pulse-on time, 35 µs pulse-off time, 17 v servo gap reference voltage, and 8 m/min wire feed rate are the optimum levels for getting high MRR, low surface roughness, less overcut and high micro channel depth. Additionally, the topographical, morphological, surface, and sub-surface characterization were also carried out to assess the surface integrity and extent of thermal damage caused by the WEDM process. With the optimum combination of process parameters a 6 × 6 micro needle array was successfully fabricated on the same substrate using micro channels as a basis of the fabrication process for the first time using the WEDM process.

Microfluidic Mechanoporation: Current Progress and Applications in Stem Cells.

Intracellular delivery, the process of transporting substances into cells, is crucial for various applications, such as drug delivery, gene therapy, cell imaging, and regenerative medicine. Among the different approaches of intracellular delivery, mechanoporation stands out by utilizing mechanical forces to create temporary pores on cell membranes, enabling the entry of substances into cells. This method is promising due to its minimal contamination and is especially vital for stem cells intended for clinical therapy. In this review, we explore various mechanoporation technologies, including microinjection, micro-nano needle arrays, cell squeezing through physical confinement, and cell squeezing using hydrodynamic forces. Additionally, we highlight recent research efforts utilizing mechanoporation for stem cell studies. Furthermore, we discuss the integration of mechanoporation techniques into microfluidic platforms for high-throughput intracellular delivery with enhanced transfection efficiency. This advancement holds potential in addressing the challenge of low transfection efficiency, benefiting both basic research and clinical applications of stem cells. Ultimately, the combination of microfluidics and mechanoporation presents new opportunities for creating comprehensive systems for stem cell processing.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Microneedles’ Device: Design, Fabrication, and Applications

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others.

Optimization of stereolithography 3D printing of microneedle micro-molds for ocular drug delivery

Microneedles (MN) have emerged as an innovative technology for drug delivery, offering a minimally invasive approach to administer therapeutic agents. Recent applications have included ocular drug delivery, requiring the manufacture of sub-millimeter needle arrays in a reproducible and reliable manner. The development of 3D printing technologies has facilitated the fabrication of MN via mold production, although there is a paucity of information available regarding how the printing parameters may influence crucial issues such as sharpness and penetration efficacy. In this study, we have developed and optimized a 3D-printed MN micro-mold using stereolithography (SLA) 3D printing to prepare a dissolving ocular MN patch. The effects of a range of parameters including aspect ratio, layer thickness, length, mold shape and printing orientation have been examined with regard to both architecture and printing accuracy of the MN micro-mold, while the effects of printing angle on needle fidelity was also examined for a range of basic shapes (conical, pyramidal and triangular pyramidal). Mechanical strength and in vitro penetration of the polymeric (PVP/PVA) MN patch produced from reverse molds fabricated using MN with a range of shapes and height, and aspect ratios were assessed, followed by ex vivo studies of penetration into excised scleral and corneal tissues. The optimization process identified the parameters required to produce MN with the sharpest tips and highest dimensional fidelity, while the ex vivo studies indicated that these optimized systems would penetrate the ocular tissue with minimal applied pressure, thereby allowing ease of patient self-administration.

Creating 3D constructs with cranial neural crest-derived cell lines using a bio-3D printer

ObjectivesThe development of bio-three-dimensional (bio-3D) printers has led to significant advances in regenerative medicine. Three-dimensional constructs, including spheroids, are maintained by extracellular matrix proteins secreted by cells so that the cells can be cultured in conditions closer to the physiological environment. This study aimed to create a useful 3D construct as a model of the dentin-pulp complex. MethodsWe examined the expression patterns of extracellular matrix proteins and cell proliferation areas in a 3D construct created using O9-1 cells derived from cranial neural crest cells of mice. The 3D construct was created by sticking the spheroid cultures onto a needle array using a bio-3D printer. ResultsCell proliferation areas along with characteristic expression of tenascin C and DMP1 were evaluated. The expression of tenascin C and DMP1 was significantly enhanced in the spheroids compared to that in two-dimensional cultures. Moreover, cell proliferation regions and tenascin C expression were confirmed in the outer layer of spheroids in the embryonic stem cell medium, with insignificant DMP1 expression being observed. Interestingly, in a 3D construct cultured in calcification-induction medium, DMP1 expression was promoted, and DMP1-positive cells existed in the outermost layer without overlapping with tenascin C expression. ConclusionsThe extracellular matrix proteins, tenascin C and DMP1, were expressed in a polarized manner in spheroids and 3D constructs, similar to the findings in the dental papilla. Therefore, these 3D constructs show potential as artificial models for studying odontogenesis.

The Emerging Trends of 3d Printing Techniques in Pharma Sector

Technology involving 3-dimensional printing has begun to revolutionize several fields, including pharmacy. In pharmacy, it offers a reliable avenue for precision medicine, dosage forms and drug delivery systems. The creation of complex drug structures with precise control over composition, shape and release kinetics, catering to individual patient needs has been possible with the intervention of this method. One significant utilization in pharmacy is the customization of dosage forms. Traditional manufacturing methods often struggle to produce tailored medications for patients with unique requirements, such as paediatric or geriatric populations. With 3D printing, pharmacists can create personalized medication with appropriate dosages, structures, and release kinetics, improving patient adherence and beneficial results. Moreover, sophisticated medication delivery systems may be created thanks to 3D printing. For instance, multi- layered tablets can be designed to release multiple drugs at different rates, optimizing treatment regimens for conditions requiring combination therapies. Furthermore, intricate structures like porous scaffolds or micro needle arrays can facilitate targeted drug delivery, enhancing bioavailability and minimizing side effects. Additionally, 3D printing facilitates the rapid prototyping of pharmaceutical formulations, accelerating the drug development process. Researchers can efficiently iterate through various designs, optimizing formulations for efficacy, stability and manufacturability. Despite its promise, challenges remain in integrating 3D printing into mainstream pharmacy practice, including regulatory hurdles, material selection and scalability issues. However, ongoing advancements in technology and collaborations between academia, industry and regulatory agencies are driving progress in overcoming these barriers. In conclusion, 3D printing technology holds immense potential to transform pharmacy by enabling personalized medicine, new dosage formulations and cutting-edge medication delivery technologies. As research and development in this field continue, the prospect of tailored pharmaceuticals tailored to individual patient needs becomes increasingly attainable.

Microneedle Patches-Integrated Transdermal Bioelectronics for Minimally Invasive Disease Theranostics.

Wearable epidermal electronics with non- or minimally-invasive characteristics can collect, transduce, communicate, and interact with accessible physicochemical health indicators on the skin. However, due to the stratum corneum layer, rich information about body health is buried under the skin stratum corneum layer, for example, in the skin interstitial fluid. Microneedle patches are typically designed with arrays of special microsized needles of length within 1000µm. Such characteristics potentially enable the access and sample of biomolecules under the skin or give therapeutical treatment painlessly and transdermally. Integrating microneedle patches with various electronics allows highly efficient transdermal bioelectronics, showing their great promise for biomedical and healthcare applications. This comprehensive review summarizes and highlights the recent progress on integrated transdermal bioelectronics based on microneedle patches. The design criteria and state-of-the-art fabrication techniques for such devices are initially discussed. Next, devices with different functions, including but not limited to health monitoring, drug delivery, and therapeutical treatment, are highlighted in detail. Finally, key issues associated with current technologies and future opportunities are elaborated to sort out the state of recent research, point out potential bottlenecks, and provide future research directions.

Multiscale hierarchical nanoarchitectonics with stereographically 3D-printed electrodes for water splitting and energy storage

The pursuit of sustainable solutions to address the global energy crisis has led to a keen interest in the advancement of cost-effective and multifunctional electrochemical systems. These systems aim to achieve both zero-carbon emissions and the dual capability to convert and store energy efficiently. The electrochemical splitting of water is one way to create carbon–neutral, clean hydrogen gas. Electrocatalysis and hydrogen evolution in general depends not only on the catalyst but also on its nano- and microstructure, which influences local chemical conditions and hydrogen gas bubble detachment. Therefore, rapid screening of not only potential catalysts but also various structured surfaces is needed for effective electrode fabrication. The fused deposition modeling (FDM) method of 3D printing is frequently used for electrode fabrication using conducting filaments; however, its micro-structuration resolution is limited. Stereolithography can produce complex and fine structures; however, the resins are not conductive and therefore the structures are not suitable for electrode fabrication. In this work, we have fabricated a substrate with high-resolution needle array architecture using stereolithographic (SLA) 3D printing and coated it with Co3Te4-CoTe2 (COT) nanofiber for water splitting and energy storage. The SLA 3D-printed cobalt telluride electrodes showed appreciable performance as a photoelectrocatalyst for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), acting as a bifunctional catalyst. We also demonstrated fabrication of a cobalt telluride based SLA 3D-printed supercapacitor device with multiscale hierarchy. The SLA 3D-printed supercapacitor device exhibited good electrochemical behavior along with high cycling stability. In general, we show here a universal method for SLA conductive electrode fabrication with hierarchical structuring of functional elements and suitable for various applications.

Creating an Array of Parallel Vortical Optical Needles

We propose a method for creating parallel Bessel-like vortical optical needles with an arbitrary axial intensity distribution via the superposition of different cone-angle Bessel vortices. We analyzed the interplay between the separation of individual optical vortical needles and their respective lengths and introduce a super-Gaussian function as their axial profile. We also analyzed the physical limitations to observe well-separated optical needles, as they are influenced by the mutual interference of the individual beams. To verify our theoretical and numerical results, we generated controllable spatial arrays of individual Bessel beams with various numbers and spatial separations by altering the spectrum of the incoming laser beam via the spatial light modulator. We demonstrate experimentally how to implement such beams using a diffractive mask. The presented method facilitates the creation of diverse spatial intensity distributions in three dimensions, potentially finding applications in specific microfabrication tasks or other contexts. These beams may have benefits in laser material processing applications such as nanochannel machining, glass via production, modification of glass refractive indices, and glass dicing.

Discharge characteristics of a microsecond pulsed underwater streamer discharge in multi-needle electrode configuration

The underwater streamer discharge has received extensive attention in the field of environmental protection, because it can generate free radicals and reactive oxygen species directly in water. The multi-needle electrode is a basic electrode configuration for achieving large-volume underwater streamer discharge. Understanding the discharge characteristics of the multi-needle electrode configuration is important for designing the large-volume discharge reactors. In this work, a multi-needle electrode that can assemble 21 needles is employed. The number of anode needles generating a streamer discharge during a single pulsed discharge and the differences in morphological characteristics between the inside and the edge of the electrode array are investigated by using an ultra-high-speed camera system. The electric field distribution of the multi-needle electrode is simulated by using the COMSOL software, and the effect of the electric field distribution on the discharge of multi-needle electrode is also studied. The discharge energy efficiency of the multi-needle electrode configuration is evaluated. It is found that the 21 needles are not discharged simultaneously during a discharge pulse. The number of discharged anode needles gradually increases and then reaches a maximum value (≤21). The maximum number of discharged anode needles during a single discharge pulse increases as the voltage and needle spacing increases. During a single discharge pulse, the filament generated from the needles at the edge of the electrode array grows longer and deviates more largely from the needle axis than that generated from the needles inside the electrode array. Such characteristics are primarily due to the disturbance of the electric field among the 21 needles. As the needle spacing decreases, the disturbance of the electric field among the 21 needles gets stronger, consequently, the discharge morphology differences between the needles at the edge and needles at the inner of the needle array become more significant, and the energy efficiency of the discharge drops remarkably.

Microstructure of macrointerfaces in shape-memory alloys

Shape-memory alloys exhibit a rich microstructure, characterized by large regions containing relatively regular laminates mixing different martensitic variants. Macrointerfaces separate these regions, and are often composed of arrays of needle-shaped martensitic domains. We formulate a model for the geometry of arrays of needles and present numerical simulations, appropriate for two compound twinned variants of martensite in a plane stress setting. One important ingredient is a new class of polyconvex energy densities with cubic symmetry, that is able to reproduce the austenitic elastic constants of the relevant materials. The energy-minimizing needle geometry is determined with tools from shape optimization. Our main finding is the “transparency effect”, which characterizes the effect of needles on domain boundaries located in front of their tip. Our numerical results are in good agreement with experimental observations.

A novel array-type microdroplet parallel-generation device.

In this study, the innovative design of a new array microdroplet parallel-generation device is proposed based on the principle of fluid inertial force using a capillary glass needle. The entire device used an electromagnetic actuator as the power source. It was designed as a 9-channel parallel array of glass needles. All glass needles feed independently, allowing different solutions to be sprayed simultaneously while effectively avoiding cross-contamination. We achieved non-contact parallel precision dispensing of nanoliter-sized microdroplet arrays using a relatively simple method. In this study, we first investigated the homogeneity of the generated droplet arrays and the stability of the device over long periods of operation. Then, the influence of the driving-voltage amplitude of the electromagnet and nozzle diameter on microdroplet generation was analyzed. Finally, a prediction model for the droplet size was developed using regression analysis to investigate the on-demand generation of droplets. In summary, the device designed in this study had a novel design, low cost, and modular assembly. It has excellent potential for applications in high precision and low-volume microdroplet-array generation.

Balanced multiphase mixing through a narrow gap

Mixing of a two-phase flow through a gap connecting adjacent channels was investigated for a variety flow rates and two gap heights. The mixing was characterized by the amount of gross liquid and net gas mass transfer from one channel to the other. The liquid mixing through the gap was calculated based on the measured mass flow rates and dye tracer concentrations at the inlet and outlet of each channel. The gas net transfer, phase fraction distributions, bubble size distributions, and gas interface velocity were measured using dual-plane wire mesh conductivity sensors at both inlets and outlets. Additionally, imaging of the fluorescent tracer dye and air bubbles were used together with Spectral Proper Orthogonal Decomposition (SPOD) to further characterize the mixing mechanisms. The water inlet Reynolds number was varied from 4 to 10×104 and the volumetric gas quality from 0 to 0.35 which resulted in gas volume fractions up to 15%. All conditions were in the bubbly flow regime. Air was introduced by a needle array producing nominally monodispersed bubbles at lower gas flow rates with broader bubble size distributions at higher gas flow rates. The Sauter mean diameter varied from 3 to 8 mm, depending on flow rates. For these balanced flows large coherent structures dominated the mixing. However, even mere O(5%) volumetric quality gas injection could significantly suppress the coherent structures reducing mixing by over 50%.

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.

Liquid Metal Droplets-Based Elastomers from Electric Toothbrush-Inspired Revolving Microfluidics.

Liquid metal (LM)-based elastomers have a demonstrated value in flexible electronics. Attempts in this area include the development of multifunctional LM-based elastomers with controllable morphology, superior mechanical performances, and great stability. Herein, inspired by the working principle of electric toothbrushes, a revolving microfluidic system is presented for the generation of LM droplets and construction of desired elastomers. The system involves revolving modules assembled by a needles array and 3D microfluidic channels. LM droplets can be generated with controllable size in a high-throughput manner due to the revolving motion-derived drag force. It is demonstrated that by employing a poly(dimethylsiloxane) (PDMS) matrix as the collection phase, the generated LM droplets can act as conductive fillers for the construction of flexible electronics directly. The resultant LM droplets-based elastomers exhibit high mechanical strength, stable electrical performance, as well as superior self-healing property benefiting from the dynamic exchangeable urea bond of the polymer matrix. Notably, due to the flexible programmable feature of the LM droplets embedded within the elastomers, various patterned LM droplets-based elastomers can be easily achieved. These results indicate that the proposed microfluidic LM droplets-based elastomers have a great potential for promoting the development of flexible electronics.