Zhuolin Xiang

Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle

The ultra-thin flexible polyimide neural probe can reduce the glial sheath growth on the probe body while its flexibility can minimize the micromotion between the probe and brain tissue. To provide sufficient stiffness for penetration purposes, we developed a drawing lithography technology for uniform maltose coating to make the maltose-coated polyimide neural probe become a stiff microneedle. The coating thicknesses under different temperature and the corresponding stiffness are studied. It has been proven that the coated maltose is dissolved by body fluids after implantation for a few seconds. Moreover, carbon nanotubes are coated on the neural probe recording electrodes to improve the charge delivery ability and reduce the impedance. Last but not least, the feasibility and recording characteristic of this ultra-thin polyimide neural probe embedded in a maltose-coated microneedle are further demonstrated by in vivo tests.

Development of vertical SU-8 microtubes integrated with dissolvable tips for transdermal drug delivery.

Polymer-based microneedles have drawn much attention in the transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approach deploys various kinds of molds to create sharp tips at the end of needles for the penetration purpose. This approach is usually time-consuming and expensive. In this study, we developed an innovative fabrication process to make biocompatible SU-8 microtubes integrated with biodissolvable maltose tips as novel microneedles for the transdermal drug delivery applications. These microneedles can easily penetrate the skins outer barrier represented by the stratum corneum (SC) layer. The drug delivery device of mironeedles array with 1000 μm spacing between adjacent microneedles is proven to be able to penetrate porcine cadaver skins successfully. The maximum loading force on the individual microneedle can be as large as 7.36 ± 0.48N. After 9 min of the penetration, all the maltose tips are dissolved in the tissue. Drugs can be further delivered via these open biocompatible SU-8 microtubes in a continuous flow manner. The permeation patterns caused by the solution containing Rhodamine 110 at different depths from skin surface were characterized via a confocal microscope. It shows successful implementation of the microneedle function for fabricated devices.

Progress of Flexible Electronics in Neural Interfacing - A Self-Adaptive Non-Invasive Neural Ribbon Electrode for Small Nerves Recording.

A novel flexible neural ribbon electrode with a self-adaptive feature is successfully implemented for various small nerves recording. As a neural interface, the selective recording capability is characterized by having reliable signal acquisitions from the sciatic nerve and its branches such as the peroneal nerve, the tibial nerve, and the sural nerve.

Development of vertical SU-8 microneedles for transdermal drug delivery by double drawing lithography technology

Polymer-based microneedles have drawn much attention in transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approaches are usually time-consuming and expensive. In this study, we developed a new double drawing lithography technology to make biocompatible SU-8 microneedles for transdermal drug delivery applications. These microneedles are strong enough to stand force from both vertical direction and planar direction during penetration. They can be used to penetrate into the skin easily and deliver drugs to the tissues under it. By controlling the delivery speed lower than 2 μl/min per single microneedle, the delivery rate can be as high as 71%.

Flexible Epineural Strip Electrode for Recording in Fine Nerves

This paper demonstrates flexible epineural strip electrodes (FLESE) for recording from small nerves. Small strip-shaped FLESE enables us to easily and closely stick on various sized nerves for less damage in a nerve and optimal recording quality. In addition, in order to enhance the neural interface, the gold electrode contacts were coated with carbon nanotubes, which reduced the impedance of the electrodes. We used the FLESEs to record electrically elicited nerve signals (compound neural action potentials) from the sciatic nerve in rats. Bipolar and differential bipolar configurations for the recording were investigated to optimize the recording configuration of the FLESEs. The successful results from differential bipolar recordings showed that the total length of FLESEs could be further reduced, maintaining the maximum recording ability, which would be beneficial for recording in very fine nerves. Our results demonstrate that new concept of FLESEs could play an important role in electroceuticals in near future.

Dense vertical SU-8 microneedles drawn from a heated mold with precisely controlled volume

Drawing lithography technology has recently become a popular technique to fabricate (3D) microneedles. The conventional drawing process shows some limitations in fabricating dense, scale-up and small microneedles. In this study, we demonstrate a new drawing lithography process from a self-loading mold which is able to overcome these challenges. Different from the conventional molds which have difficult alignment and loading issues, a released SU-8 membrane is attached onto a SU-8 coated wafer to generate an innovative self-loading mold. The physically distinct SU-8 colloid in this mold successfully avoids the merging of the microneedle tips in the drawing process. Meanwhile, the same SU-8 colloid in mold can provide microneedles with uniform lengths on a large surface area. Furthermore, a low temperature drawing process with this improved technique prevents sharp tips from bending during the solidification stage. Remarkably, this new drawing lithography technology can fabricate microneedles with various lengths and they are strong enough to penetrate the outermost skin layer, namely the stratum corneum. The spacing between two adjacent microneedles is optimized to maximize the penetration rate through the skin. Histology images and drug diffusion testing demonstrate that microchannels are successfully created and the drugs can permeate the tissue under the skin. The fabricated microneedles are demonstrated to deliver insulin in vivo and lower blood glucose levels, suggesting future possible applications for minimally invasive transdermal delivery of macromolecules.

Mapping of Small Nerve Trunks and Branches Using Adaptive Flexible Electrodes

Selective stimulation is delivered to the sciatic nerve using different paris of contacts on a split‐ring electrode, while simulatneous recordings are acquired by the neural ribbon electrodes on three different branches. Two hook electrodes are also implanted in the muscle to monitor the activated muscle responses. It shows that the high precision implantation of electrodes, increases the efficacy and reduces the incidence of side effects.

Development of Silicon Probe With Acute Study on In Vivo Neural Recording and Implantation Behavior Monitored by Integrated Si-Nanowire Strain Sensors

The silicon probe with highly P-doped Si electrodes was realized on 8-in Silicon on insulator wafer through standard Complementary metal-oxide semiconductor process. By leveraging the same thin Si device layer (~100 nm), the built-in piezoresistive Si-nanowires (SiNWs) configured in full-bridge structure were also equipped along the probe shank for strain sensing. After additional coatings of nanocomposite (Carbon nanotubes + Au nanoparticles) on silicon electrodes, the functionality of neural recording was validated with a low noise level (<;20 μV) during in vivo neural recording on rat brain (CA1 region). The additional capability of monitoring probe mechanical behavior was first verified through the probe buckling experiments and further examined with implantations on rat brain (S1 region). Besides the large buckling mechanics, the physiological brain micromotion (e.g., caused by respiration) was successfully picked up by integrated SiNWs strain sensors, which would provide the research platform to practically understand the correlation between the electrical neural signal and the brain micromotion.

Microneedle Array Integrated With CNT Nanofilters for Controlled and Selective Drug Delivery

An innovative process of integrating microneedle array with carbon nanotube (CNT) nanofilters is developed for a novel transdermal drug delivery device with nanometer-scale selectivity and control mechanism. The SU-8 microneedle array is fabricated by the double drawing lithography process. This microneedle array is capable of penetrating stratum corneum (SC) layer. Then, drug molecules can selectively pass through CNT nanofilters with the aid of pressure, or an electric field, and are effectively delivered into the tissues under the SC layer. The CNT bundles integrated within the microneedle array act as nanofilters to block particles and molecules larger than the inner diameter of the CNTs. Moreover, the CNT nanofilters can selectively control the delivered drugs when they are under various electric fields. Three kinds of biomolecules, e.g., glucose, insulin, and hemagglutininare are investigated. The results demonstrate that the proposed novel transdermal drug delivery device can effectively deliver drug molecules in a selectively control mechanism.

Development of a disposable and flexible microneedle-fluidic-system with finger driven drug loading and delivery functions

Patch-based transdermal drug delivery technology offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections related to issues such as patient acceptability and injection safety. In this study, we developed a flexible and disposable microneedle-fluidic-system (MFS) which can achieve finger driven on-chip drug loading and delivery functions by integrating Polydimethylsiloxane (PDMS) based microfluidic dispensing networks, check valves, micro pump and SU-8 microneedles in a patch device. The control of particular loading or delivery volume for drugs is provided in terms of finger pressing to a micro pump with a given dimension. The in vitro mechanical testing, penetration testing and delivery testing prove the device functionalities. The local inflammation phenomenon of rats has been ameliorated with the aid of successful diclofenac deliver by our MFS patch.