Lei Ren

Fabrication of Micro-Needle Electrodes for Bio-Signal Recording by a Magnetization-Induced Self-Assembly Method

Micro-needle electrodes (MEs) have attracted more and more attention for monitoring physiological electrical signals, including electrode-skin interface impedance (EII), electromyography (EMG) and electrocardiography (ECG) recording. A magnetization-induced self-assembling method (MSM) was developed to fabricate a microneedle array (MA). A MA coated with Ti/Au film was assembled as a ME. The fracture and insertion properties of ME were tested by experiments. The bio-signal recording performance of the ME was measured and compared with a typical commercial wet electrode (Ag/AgCl electrode). The results show that the MA self-assembled from the magnetic droplet array under the sum of gravitational surface tension and magnetic potential energies. The ME had good toughness and could easily pierce rabbit skin without being broken or buckling. When the compression force applied on the ME was larger than 2 N, ME could stably record EII, which was a lower value than that measured by Ag/AgCl electrodes. EMG signals collected by ME varied along with the contraction of biceps brachii muscle. ME could record static ECG signals with a larger amplitude and dynamic ECG signals with more distinguishable features in comparison with a Ag/AgCl electrode, therefore, ME is an alternative electrode for bio-signal monitoring in some specific situations.

Fabrication of a Micro-Needle Array Electrode by Thermal Drawing for Bio-Signals Monitoring

A novel micro-needle array electrode (MAE) fabricated by thermal drawing and coated with Ti/Au film was proposed for bio-signals monitoring. A simple and effective setup was employed to form glassy-state poly (lactic-co-glycolic acid) (PLGA) into a micro-needle array (MA) by the thermal drawing method. The MA was composed of 6 × 6 micro-needles with an average height of about 500 μm. Electrode-skin interface impedance (EII) was recorded as the insertion force was applied on the MAE. The insertion process of the MAE was also simulated by the finite element method. Results showed that MAE could insert into skin with a relatively low compression force and maintain stable contact impedance between the MAE and skin. Bio-signals, including electromyography (EMG), electrocardiography (ECG), and electroencephalograph (EEG) were also collected. Test results showed that the MAE could record EMG, ECG, and EEG signals with good fidelity in shape and amplitude in comparison with the commercial Ag/AgCl electrodes, which proves that MAE is an alternative electrode for bio-signals monitoring.

Rapid fabrication of microneedles using magnetorheological drawing lithography

Microneedles are micron-sized needles that are widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. In this study, we present a novel magnetorheological drawing lithography (MRDL) method to efficiently fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. With the assistance of an external magnetic field, the 3D structure of a microneedle can be directly drawn from a droplet of curable magnetorheological fluid. The formation process of a microneedle consists of two key stages, elasto-capillary self-thinning and magneto-capillary self-shrinking, which greatly affect the microneedle height and tip radius. Penetration and fracture tests demonstrated that the microneedle had sufficient strength and toughness for skin penetration. Microneedle arrays and a bio-inspired microneedle were also fabricated, which further demonstrated the versatility and flexibility of the MRDL method. STATEMENT OF SIGNIFICANCE Microneedles have been widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. Furthermore, most researchers have focused on the biomedical applications of microneedles but have given little attention to the optimization of the fabrication process. This research presents a novel magnetorheological drawing lithography (MRDL) method to fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. In this proposed technique, a droplet of curable magnetorheological fluid (CMRF) is drawn directly from almost any substrate to produce a 3D microneedle under an external magnetic field. This method not only inherits the advantages of thermal drawing approach without the need for a mask and light irradiation but also eliminates the requirement for drawing temperature adjustment. The MRDL method is extremely simple and can even produce the complex and multiscale structure of bio-inspired microneedle.

Effect of honeybee stinger and its microstructured barbs on insertion and pull force

Worker honeybee is well-known for its stinger with microscopic backward-facing barbs for self-defense. The natural geometry of the stinger enables painless penetration and adhesion in the human skin to deliver poison. In this study, Apis cerana worker honeybee stinger and acupuncture microneedle (as a barbless stinger) were characterized by Scanning Electron Microscope (SEM). The insertion and pull process of honeybee stinger into rabbit skin was performed by a self-developed mechanical loading equipment in comparison with acupuncture needle. In order to better understand the insertion and pull mechanisms of the stinger and its barbs in human multilayer skin, a nonlinear finite element method (FEM) was conducted. Experimental results showed that the average pull-out force of the stinger was 113.50mN and the average penetration force was only 5.75mN. The average penetration force of the stinger was about one order of magnitude smaller than that of an acupuncture microneedle while the average pull-out force was about 70 times larger than that of an acupuncture microneedle. FEM results showed that the stress concentrations were around the stinger tip and its barbs during the insertion process. The barbs were jammed in and torn the skin during the pull process. The insertion force of the stinger was greatly minimized due to its ultrasharp stinger tip and barbs while the pull force was seriously enhanced due to the mechanical interlocking of the barbs in the skin. These excellent properties are mainly a result of optimal geometry evolved by nature. Such finding may provide an inspiration for the further design of improved tissue adhesives and micro-needles for painless transdermal drug delivery and bio-signal recording.

Fabrication of Magnetic Nanofibers by Needleless Electrospinning from a Self-Assembling Polymer Ferrofluid Cone Array

Magnetic nanofiber has been widely applied in biomedical fields due to its distinctive size, morphology, and properties. We proposed a novel needleless electrospinning method to prepare magnetic nanofibers from the self-assembling “Taylor cones” of poly(vinyl pyrrolidone) (PVP)/Fe3O4 ferrofluid (PFF) under the coincident magnetic and electric fields. The results demonstrated that a static PFF Rosensweig instability with a conical protrusion could be obtained under the magnetic field. The tip of the protrusion emitted an electrospinning jet under the coincident magnetic and electric fields. The needleless electrospinning showed a similar process phenomenon in comparison with conventional electrospinning. The prepared nanofibers were composed of Fe3O4 particles and PVP polymer. The Fe3O4 particles aggregated inside and on the surface of the nanofibers. The nanofibers prepared by needleless electrospinning exhibited similar morphology compared with the conventionally electrospun nanofibers. The nanofibers also exhibited good ferromagnetic and magnetic field responsive properties.

Fabrication of Composite Microneedle Array Electrode for Temperature and Bio-Signal Monitoring

Body temperature and bio-signals are important health indicators that reflect the human health condition. However, monitoring these indexes is inconvenient and time-consuming, requires various instruments, and needs professional skill. In this study, a composite microneedle array electrode (CMAE) was designed and fabricated. It simultaneously detects body temperature and bio-signals. The CMAE consists of a 6 × 6 microneedles array with a height of 500 μm and a base diameter of 200 μm. Multiple insertion experiments indicate that the CMAE possesses excellent mechanical properties. The CMAE can pierce porcine skin 100 times without breaking or bending. A linear calibration relationship between temperature and voltage are experimentally obtained. Armpit temperature (35.8 °C) and forearm temperature (35.3 °C) are detected with the CMAE, and the measurements agree well with the data acquired with a clinical thermometer. Bio-signals including EII, ECG, and EMG are recorded and compared with those obtained by a commercial Ag/AgCl electrode. The CMAE continuously monitors bio-signals and is more convenient to apply because it does not require skin preparation and gel usage. The CMAE exhibits good potential for continuous and repetitive monitoring of body temperature and bio-signals.

Fabrication of Flexible Microneedle Array Electrodes for Wearable Bio-Signal Recording

Laser-direct writing (LDW) and magneto-rheological drawing lithography (MRDL) have been proposed for the fabrication of a flexible microneedle array electrode (MAE) for wearable bio-signal monitoring. Conductive patterns were directly written onto the flexible polyethylene terephthalate (PET) substrate by LDW. The microneedle array was rapidly drawn and formed from the droplets of curable magnetorheological fluid with the assistance of an external magnetic field by MRDL. A flexible MAE can maintain a stable contact interface with curved human skin due to the flexibility of the PET substrate. Compared with Ag/AgCl electrodes and flexible dry electrodes (FDE), the electrode–skin interface impedance of flexible MAE was the minimum even after a 50-cycle bending test. Flexible MAE can record electromyography (EMG), electroencephalography (EEG) and static electrocardiography (ECG) signals with good fidelity. The main features of the dynamic ECG signal recorded by flexible MAE are the most distinguishable with the least moving artifacts. Flexible MAE is an attractive candidate electrode for wearable bio-signal monitoring.

Needleless electrospray of magnetic film from magnetization-induced cone array

ABSTRACT Electrospray is a simple and versatile approach to deposit thin-films. Traditionally, electrospray is achieved through capillary nozzle electrode to create fluid jet. Here, we report a novel needleless electrospray approach to continuously deposit the magnetic film from the magnetization-induced self-assembling cone array of poly(vinyl pyrrolidone) (PVP)/Fe3O4 ferrofluid without any nozzle and feed unit. A spiral tower is used to pump the PVP/Fe3O4 ferrofluid and a 3D peak-cluster is self-assembled on the tip surface under an external magnetic field. The multiple and parallel jets can be continuously emitted from the cone array of 3D peak-cluster, and get deposited on the aluminum foil as a smooth magnetic film when a high-voltage electric field is further applied. This needleless electrospray approach is simple, and cost-effective with a high productivity. The prepared magnetic film mainly composed of Fe3O4 nanoparticles and PVP polymer exhibits superparamagnetic property and good magnetic field responsive property.

Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

Abstract To date, only approximately 20 drugs synthesized with small molecules have been approved by the FDA for use in traditional transdermal patches (TTP) owing to the extremely low permeation rate of the skin barrier for macromolecular drugs. A novel touch-actuated microneedle array patch (TMAP) was developed for transdermal delivery of liquid macromolecular drugs. TMAP is a combination of a typical TTP and a solid microneedle array (MA). High doses of liquid drug formulations, especially heat-sensitive compounds can be easily filled and stored in the drug reservoir of TMAPs. TMAP can easily penetrate the skin and automatically retract from it to create microchannels through the stratum corneum (SC) layer using touch-actuated ‘press and release’ actions for passive permeation of liquid drugs. Comparison of subcutaneous injection, TTP, solid MA, and dissolvable MA, indicated that insulin-loaded TMAP exhibited the best hypoglycemic effect on type 1 diabetic rats. A ‘closed-loop’ permeation control was also provided for on-demand insulin delivery based on feedback of blood glucose levels (BGLs). Twenty IU-insulin-loaded TMAP maintained the type 1 diabetic rats in a normoglycemic state for approximately 11.63 h, the longest therapeutic duration among all previously reported results on microneedle-based transdermal patches. TMAP possesses excellent transdermal drug delivery capabilities.

Additive Manufacturing of Honeybee-Inspired Microneedle for Easy Skin Insertion and Difficult Removal

With natural evolution, honeybee stinger with microbarbs can easily penetrate and trap in the skin of hostile animals to inject venom for self-defense. We proposed a novel three-dimensional additive manufacturing method, namely magnetorheological drawing lithography, to efficiently fabricate a bioinspired microneedle imitating a honeybee stinger. Under the assistance of an external magnetic field, a parent microneedle was directly drawn on the pillar tip, and tilted microbarbs were subsequently formed on the four sides of the parent microneedle. Compared with the barbless microneedle, the microstructured barbs enable the bioinspired microneedle for easy skin insertion and difficult removal. The extraction-penetration force ratio of the bioinspired microneedle was triple that of the barbless microneedle. The stress concentration at the barbs helps to reduce the insertion force of the bioinspired microneedle by minimizing the frictional force, whereas it increases the adhesion force by interlocking the barbs in the tissue during retraction. Such finds may provide an inspiration for further design of barbed microtip-based microneedles for tissue adhesion, transdermal drug delivery, biosignal recording, and so on.