Jingbo Yang, Zhipeng Chen, Rui Ye, Jiyu Lia,, Yinyan Lin, Jie Gao, Lei Ren, Bin Liu and Lelun Jiang* Drug Delivery Volume 25, 2018 - Issue 1, 1728–1739 原文链接：https://doi.org/10.1080/10717544.2018.1507060 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. Keywords: Transdermal drug delivery; microneedle array; traditional transdermal patch; insertion; diabetes; insulin; closed-loop control

Zhipeng Chen, Yinyan Lin, Weihsien Lee, Lei Ren, Bin Liu, Liang Liang, Zhi Wang, and Lelun Jiang* ACS Appl. Mater. Interfaces  10, 35, 29338-29346 原文链接：https://pubs.acs.org/doi/10.1021/acsami.8b09563 Abstract 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. Keywords: bioinspired; finite element analysis; magnetorheological drawing lithography; microneedle; penetration; retraction    

Shujia Xu, Lei Ren, Bin Liu, Jiarui Wang, Biao Tang, Wei Zhou, Lelun Jiang* Applied Surface Science Volume 454, 1 October 2018, Pages 16-22 原文链接：https://doi.org/10.1016/j.apsusc.2018.05.144 Abstract A novel approach named laser induced molten transfer (LIMT) was proposed to rapidly fabricate the metallic patterns on the insulating substrates with high bonding strength by nanosecond laser direct writing. The laser beam selectively irradiated and melted the donor foil and transferred the molten droplets on the target substrate by the induced laser shock, resulting in the formation of designed metallic pattern. The processing parameters were firstly optimized, the morphology of transferred pattern was characterized, and the pattern conductivity and bonding strength were investigated experimentally. The optimized processing parameters for the fabrication of high-quality pattern were the scanning speed of 750 mm/s, laser power of 21 W, and scanning interval of 15 μm. This transferred copper pattern was porous and composed of aggregated micro droplets. The copper pattern surface was homogeneously rough and its edges were clear. The electrical resistivity of transferred pattern was approximately 8 times of the bulk copper due to the oxidation of copper droplets and porosity of pattern. The transferred copper pattern has good bonding strength on the glass substrate due to the existence of a copper-glass recast layer. A micro-heater pattern was integrated in a microfluidic chip, which demonstrated the LIMT approach can selectively transfer pattern on 3D surface. LIMF can successfully transfer the pure metal and alloy patterns on the various target substrates, even the flexible substrate, which further exhibited its excellent versatility and flexibility. Keywords: Metallization; Pattern; Laser-direct writing; Glass; Polyimide; Bonding strength  

Hongjian Wang, Bin Liu, Weilong Huang, Zi Lin, Jie Luo, Yan Li, Lin Zhuang, Wei Wang, Lelun Jiang* Journal of Magnetism and Magnetic Materials Volume 452, 15 April 2018, Pages 1-4 原文链接：https://doi.org/10.1016/j.jmmm.2017.12.035 Abstract A novel approach, continuous needleless electrospinning from the tips of magnetization-induced self-assembling PVA/ferrofluid cone array, was proposed to prepare magnetic nanofibers. A PVA/ferrofluid was synthesized, the needleless electrospinning process was observed, and the morphology and magnetic properties of magnetic nanofibers were investigated. The results showed that the PVA/ferrofluid could remain stable and homogeneous for 21 days under the magnetic field gradient (2.2 mT/mm). “Taylor cone” array of PVA/ferrofluid was self-assembled under both the magnetic and electric fields. As the electric voltage reached 25 kV, the jets were emitted from the “Taylor cone” array, resulting in needleless electrospinning of magnetic nanofibers. Magnetic nanofibers were homogeneous and continuous with an average diameter of 73.6 nm. Magnetic nanofibers showed a good magnetic response property and relatively high saturated magnetization (1.71 emu/g), which is expected to be applied in the biomedical field. Keywords: Nanocomposites; Magnetic nanofibers; Needleless electrospinning; Self-assembling; Nanoparticles; Ferrofluid

Lei Ren#, Shujia Xu#, Jie Gao, Zi Lin, Zhipeng Chen, Bin Liu, Liang Liang, Lelun Jiang* Sensors 2018, 18(4), 1191 原文链接：https://doi.org/10.3390/s18041191 Abstract 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. Keywords: laser-direct writing; magneto-rheological drawing lithography; microneedle array; electrode; bio-signal

Yiwei Sun#, Lei Ren#, Lelun Jiang, Yong Tang, Bin Liu* Sensors 2018, 18(4), 1193 原文链接：https://doi.org/10.3390/s18041193 Abstract 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. Keywords: microneedle array; composite electrode; body temperature; bio-signal

Hongjian Wang, Zhipeng Chen, Bin Liu, Lei Ren, Lin Zhuang, Kang Sun & Lelun Jiang* Materials and Manufacturing Processes Volume 33, 2018 - Issue 10 原文链接：https://doi.org/10.1080/10426914.2017.1415446 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. Keywords: Cone array, electrospray, ferrofluid, film, magnetic field, nanoparticles, self-assembling, superparamagnetism

Zhipeng Chen,Lei Ren, Jiyu Li, Lebin Yao, Yan Chen, Bin Liu, Lelun Jiang* Acta Biomaterialia Volume 65, January 2018, Pages 283-291 原文链接：https://doi.org/10.1016/j.actbio.2017.10.030 Abstract 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. Keywords: Microneedle array; Bio-inspired microneedle; Magnetorheological fluid; Self-assembly; Drawing lithography