Arrays of hollow out-of-plane microneedles for drug delivery

Drug delivery based on MEMS technology requires an invasive interface such as microneedles, which connects the microsystem with the biological environment. Two-dimensional arrays of rigid hollow microneedles have been fabricated from single-crystal silicon using a combination of deep reactive ion etching and isotropic etching techniques. The fabricated needles are typically 200 /spl mu/m long with a wide base and a channel diameter of 40 /spl mu/m. The fabrication process allows creating either blunt needles or needles with sharp tips. Their shape and size make these needles extremely suitable for minimally invasive painless epidermal drug delivery. MEMS technology allows for batch fabrication and integration with complex microsystems. Fluid has been successfully injected 100 /spl mu/m deep into sample tissue through arrays of microneedles. Needle breakage did not occur during this procedure. Experiments have shown that the modified Bernoulli equation is a good model for liquid flowing through the narrow microneedle lumen.     

Silicon micromachined hollow microneedles for transdermal liquid transport

This paper presents a novel process for the fabrication of out-of-plane hollow microneedles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different, lithography-defined tip curvature. In this study, the length of the needles varied between 150 and 350 micrometers. The widest dimension of the needle at its base was 250 /spl mu/m. Preliminary application tests of the needle arrays show that they are robust and permit skin penetration without breakage. Transdermal water loss measurements before and after microneedle skin penetration are reported. Drug delivery is increased approximately by a factor of 750 in microneedle patch applications with respect to diffusion alone. The feasibility of using the microneedle array as a blood sampler on a capillary electrophoresis chip is demonstrated.     

Optimizing hollow microneedles arrays aimed at transdermal drug delivery

Microneedles as a means of transdermal drug delivery is a very promising technology that has been under development in recent years. Much research has been undertaken on the subject, but the quantity of available information makes determining crucial factors for their optimization difficult. This review article gathers available information concerning the mechanics and fluidics of microneedles and provides the reader with important summarized information to take into consideration when designing microneedles systems intended for transdermal drug delivery.     

Innovative design of hollow polymeric microneedles for transdermal drug delivery

Hypodermic injections give the best results in terms of drug administration efficiency, but benefit from a negative image among patients due to the fear of pain linked to needles. Transdermal drug delivery (TDD) has thus been greatly developed in the past ten years in order to be able to by-pass the skin protective layers in a minimally invasive way. With the advent of micro electro mechanical systems, opportunities have appeared, particularly in the area of microneedles. In this paper we present a new design of hollow polymeric microneedles aimed at being used for TDD by allowing injection of a liquid in the non-innerve part of the dermis. The design has been studied in order to be able to manufacture these microneedles arrays using techniques that may be applicable to industrial production at low cost. The envisioned microfabrication processes and their stacking are presented which involve injection micromolding and excimer laser ablation. Microneedles are also numerically characterized in terms of mechanics and microfluidics showing that the design also involves interesting features in terms of needles resistance and microfluidic. Due to the innovative double-molding technique, the micro-needles are indeed emptied leaving a cavity. An outlet channel on the side of the needle allows fluid flowing out of the needles. The characteristics of this outlet channel contribute to flow homogenization when several needles are placed in an array pattern. This microneedle design thus combines interesting characteristics in terms of ease of fabrication at large scale, mechanical resistance and fluid dynamics.

     

Innovative design of hollow polymeric microneedles for transdermal drug delivery

Hypodermic injections give the best results in terms of drug administration efficiency, but benefit from a negative image among patients due to the fear of pain linked to needles. Transdermal drug delivery (TDD) has thus been greatly developed in the past ten years in order to be able to by-pass the skin protective layers in a minimally invasive way. With the advent of micro electro mechanical systems, opportunities have appeared, particularly in the area of microneedles. In this paper we present a new design of hollow polymeric microneedles aimed at being used for TDD by allowing injection of a liquid in the non-innerve part of the dermis. The design has been studied in order to be able to manufacture these microneedles arrays using techniques that may be applicable to industrial production at low cost. The envisioned microfabrication processes and their stacking are presented which involve injection micromolding and excimer laser ablation. Microneedles are also numerically characterized in terms of mechanics and microfluidics showing that the design also involves interesting features in terms of needles resistance and microfluidic. Due to the innovative double-molding technique, the micro-needles are indeed emptied leaving a cavity. An outlet channel on the side of the needle allows fluid flowing out of the needles. The characteristics of this outlet channel contribute to flow homogenization when several needles are placed in an array pattern. This microneedle design thus combines interesting characteristics in terms of ease of fabrication at large scale, mechanical resistance and fluid dynamics.     

Investigations of development process of high hollow beveled microneedles using a combination of ICP RIE and dicing saw

Micromachined needles provide a promising technology for painless delivery of molecules or foreign substance into a living cell. Over the recent years, a variety of different microneedle shapes and materials have been studied and have shown their facility to disrupt stratum corneum layer to increase the skin permeability. In this paper, we described an alternative process to fabricate high and beveled hollow out-of-plane microneedles. Silicon microneedles dimensions are 40–60 μm in inner diameter, 150–200 μm in outer diameter and over 700 μm in height. Tip angles reached are from 30° to 45°.     

A novel microdevice for the treatment of hydrocephalus: design and fabrication of an array of microvalves and microneedles

We present an implantable, microfabricated device for the treatment of hydrocephalus. Hydrocephalus is a medical condition, in which an abnormal accumulation of cerebrospinal fluid (CSF, a water-like fluid that circulates around and protects the brain and spinal cord.) occurs in the brain. The novel microdevice presented here mimics the function of natural one-way valves, arachnoid villi, found in the human brain. Hence, we name it microfabricated arachnoid villi (MAV). The MAV consists of an array of one-way microvalves and hollow microneedles. The one-way microvalves control flow based on pressure differential. A Parylene microvalve array with a dome petal geometry was designed and fabricated. Initial flow tests demonstrated the desired low cracking pressure of the valve and a sufficient mechanical stability. The hollow microneedle array was designed to pierce the dura mater membrane (A tough fibrous membrane covering the brain and the spinal cord and lining the inner surface of the skull.) and provide a conduit for CSF. An SU-8 microneedle array was designed and successfully microfabricated. The innovative MAV may open a new era in the treatment of hydrocephalus.     

Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications

In this paper, we present a new design of hollow, out-of-plane polymeric microneedle with cylindrical side-open holes for transdermal drug delivery (TDD) applications. A detailed literature review of existing designs and analysis work on microneedles is first presented to provide a comprehensive reference for researchers working on design and development of micro-electromechanical system (MEMS)-based microneedles and a source for those outside the field who wish to select the best available microneedle design for a specific drug delivery or biomedical application. Then, the performance of the proposed new design of microneedles is numerically characterized in terms of microneedle strength and flow rate at applied inlet pressures. All the previous designs of hollow microneedles have side-open holes in the lumen section with no integrated reservoir on the same chip. We have proposed a new design with side-open holes in the conical section to ensure drug delivery on skin insertion. Furthermore, the present design has an integrated drug reservoir on the back side of the microneedles. Since MEMS-based, hollow, side-open polymeric microneedles with integrated reservoir is a new research area, there is a notable lack of applicable mathematical models to analytically predict structural and fluid flow under various boundary conditions. That is why, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been used to facilitate design optimization before fabrication. The analysis has involved simulation of structural and CFD analysis on three-dimensional model of microneedle array. The effect of axial and transverse loading on the microneedle during skin insertion is investigated in the stress analysis. The analysis predicts that the resultant stresses due to applied bending and axial loads are in the safe range below the yield strength of the material for the proposed design of the microneedles. In CFD analysis, fluid flow rate and pressure drop in the microneedles at applied inlet pressures are numerically and theoretically investigated. The CFD analysis predicts uniform flow through the microneedle array for each microneedle. Theoretical and numerical results for the flow rate and pressure drop are in close agreement with each other, thereby validating the CFD analysis. For the proposed design of microneedles, feasible fabrication techniques such as micro-hot embossing and ultraviolet excimer laser methods are proposed. The results of the present theoretical study provide valuable benchmark and prediction data to fabricate optimized designs of the polymeric, hollow microneedles, which can be successfully integrated with other microfluidic devices for TDD applications.     

基于空心微针阵列的连续监测葡萄糖传感器

研制了一种基于空心微针阵列并可微痛刺入皮下实时连续监测人体血糖浓度的葡萄糖传感器.微针阵列由等间距的三根微针组成,分别作为工作电极、辅助电极和参比电极,其中工作电极与辅助电极采用表面溅射了Ti/Pt的空心不锈钢微针来制作,采用戊二醛-牛血清白蛋白交联法将葡萄糖氧化酶固定并仅置于作为工作电极的针尖通孔处;参比电极采用Ag/AgCl实心微针制作.测试结果表明:葡萄糖浓度在0～21 mmol·L-1范围内传感器输出电流为线性,灵敏度为0.575 μA/(mmol·L-1),响应时间为16s,且具有很好的抗干扰性.     

Low-noise gaas MESFET optimization using an orthogonal array approach

This article presents an experimental optimization of the noise figure of small-signal self-aligned FETs. An L₁₈ orthogonal array has been used to find the main effects of specific device parameters on noise performance at 18 GHz. This knowledge has been used to find an alternative device which shows a ～0.7-dB improvement in noise measure without requiring major process changes. Hybrid low-noise amplifiers built with the improved FETs confirm the noise performance and show record power performance for high dynamic range applications. © 1994 John Wiley & Sons, Inc.     

A piezoelectric energy harvester using an arc-shaped piezoelectric cantilever beam array

Microsystem Technologies - The piezoelectric energy harvester (PEH) has shown important practical value in numerous fields including, but not limited to communication, transportation, and military...     

A real-time vision system using an integrated memory array processor prototype

This paper describes a real-time vision system (RVS) architecture and performance and its use of an integrated memory array processor (IMAP) prototype. This prototype integrates eight 8-bit processors and a 144-kbit SRAM on a single chip. The RVS was developed with 64 IMAP prototypes connected in series in a 512 processor-system configuration. A host workstation can access the memory on the IMAP prototypes directly through a random access port. Images are inputted and outputted at high speed through serial access ports. The RVS performance is shown in real-time road-image processing and in a neural network simulation, as well as in low-level image processing algorithms, such as filtering, histograms, discrete cosine transform (DCT), and rotation. The RVS image processing is shown to be much faster than the video rate.     

超薄磁力搅拌器的设计与实现

设计了一种将电能直接转换为磁能的磁力搅拌器。通过单片机控制L6219DS产生电流时序,采用4个螺旋线圈按照时序产生8个方向周期性变化的磁场,进而控制搅拌子的转动。由于省略了传统的机械部分,使得磁力搅拌器的厚度降为1cm,具有质量轻、搅拌速度稳定的优点。     

Characterization of surface micromachined metallic microneedles

The purpose of the paper is to provide quantitative characterization of metallic microneedles. Mechanical and fluid flow experiments were performed to evaluate the buckling force, the penetration force, and the pressure versus flow rate characteristics of the microneedles. The microneedle design variations characterized included varying the shaft lengths, varying the tip taper angles/geometries, and the inclusion of micromechanical barbs. The penetration force was found to range from 7.8 gF for a microneedle of shaft length 500 /spl mu/m, to 9.4 gF for a length of 1500 /spl mu/m, both with a tip taper angle of 30/spl deg/. Microneedles with a linear tip taper angle of 30/spl deg/ penetrated 95 +% of the time without failure. The microneedles with a 15/spl deg/ and 20/spl deg/ linear tip taper penetrated 10% and 25% of the time, respectively. The buckling force was found to be 98.4 gF for a 500 /spl mu/m long microneedle shaft, 72.3 gF for a needle of shaft length 1000 /spl mu/m, and 51.6 gF for a 1500 /spl mu/m long shaft. The results demonstrate that the penetration force was 7.9% of the buckling force for 500 /spl mu/m long shafts, 11.6% for a 1000 /spl mu/m long shaft, and 18.2% for a 1500 /spl mu/m long microneedle shafts. The microneedle fluid flow characteristics were studied. An inlet pressure of 49.0 Pa was required for a flow rate of 1000 /spl mu/L/h and 243.0 Pa for a flow rate of 4000 /spl mu/L/h using air as the fluid medium. For water, an average pressure of 30.0 kPa was required for a flow rate of 1000 /spl mu/L/h and 106.0 kPa for a flow rate of 4000 /spl mu/L/h.     

Measurement of vorticity in the surface layer using an acoustic echo sounder array

The earth's atmospheric surface layer is usually defined as that region of the lower atmosphere (generally below about 10 m above the earth's surface) where surface friction causes vertical fluxes of heat, moisture and momentum to be constant with height. Within the surface layer, either in response to surface friction or to the atmosphere above, horizontal circular eddies often develop. These circular motions may provide the source of rotation for dust devils so often seen on hot and dry days particularly in desert regions. Also, at larger scales ($\text{～ 1 km in diameter}$) regions of warm and therefore buoyant upward moving air, called thermal plumes, may acquire rotation. These plumes may extend from the earth's surface to more than a kilometer in height on a warm afternoon. Fluid dynamicists quantify this horizontal rotation with a parameter known as the vertical component of vorticity. Vorticity is very difficult to measure in the earth's atmosphere at scales of close to a kilometer because the calculation involves wind-speed differences over horizontal distances of about 500 m. The winds must be measured quite accurately because the differences can be quite small and, therefore, the errors in these measurements are often quite large. This work describes a method of measuring vertical vorticity at scales down to 500 m using an array of three acoustic sounders about 2 m above the earth's surface which overcomes some of the accuracy problems mentioned above. We relate these vorticity measurements to other atmospheric parameters and compute temporal spectra of these quantities to help explain the relationship between vorticity, thermal plume activity, and the smaller-scale dust devils.     

A large screen matrix display using an array of ac plasma display panels

A direct-view large-screen matrix type display using an array of ac plasma display modules has been developed. Its resolution can reach 160 lines m^?1 and 230 lines m^?1: the screen area being expanded according to the user's requirements. It can be used in the areas of alphanumerics and graphics. This paper describes its structure, drive circuit, and some design considerations.     

基于直列式交错微电极阵列的细胞电融合

提出了一种基于交错式齿状微电极阵列的微流控细胞电融合芯片。利用COMSOL Multiphysics仿真软件,对电场强度有重要影响的微电极几何参数进行了仿真分析,并由此提出了优化的微电极阵列结构。选择SoI硅片的顶层低阻硅加工获得了微电极阵列。实验结果表明:该芯片中采用的直列式微通道结构避免了原有芯片存在的转角易堵塞问题。芯片能够在低电压条件下实现细胞排队和融合过程,具有较高的融合效率。