Microinfusion Using Hollow Microneedles

Purpose The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. Methods Glass microneedles were inserted to a depth of 720–1080 μm into human cadaver skin to microinfuse sulforhodamine solution at constant pressure. Flow rate was determined as a function of experimental parameters, such as microneedle insertion and retraction distance, infusion pressure, microneedle tip geometry, presence of hyaluronidase, and time. Results Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15–96 μl/h. Partial retraction of microneedles increased flow rate up to 11.6-fold. Infusion flow rate was also increased by greater insertion depth, larger infusion pressure, use of a beveled microneedle tip, and the presence of hyaluronidase such that flow rates ranging from 21 to 1130 μl/h were achieved. These effects can be explained by removing or overcoming the large flow resistance imposed by dense dermal tissue, compressed during microneedle insertion, which blocks flow from the needle tip. Conclusions By partially retracting microneedles after insertion and other methods to overcome flow resistance of dense dermal tissue, protocols can be designed for hollow microneedles to microinfuse fluid at therapeutically relevant rates.     

Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems

Polydimethylsiloxane (PDMS Sylgard 184, Dow Corning Corporation) pre-polymer was combined with increasing amounts of cross-linker (5.7, 10.0, 14.3, 21.4, and 42.9 wt.%) and designated PDMS1, PDMS2, PDMS3, PDMS4, and PDMS5, respectively. These materials were processed by spin coating and subjected to common micro-fabrication, micro-machining, and biomedical processes: chemical immersion, oxygen plasma treatment, sterilization, and exposure to tissue culture media. The PDMS formulations were analyzed by gravimetry, goniometry, tensile testing, nano-indentation, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Spin coating of PDMS was formulation dependent with film thickness ranging from 308 microm on PDMS1 to 171 microm on PDMS5 at 200 revolutions per minute (rpm). Ultimate tensile stress (UTS) increased from 3.9 MPa (PDMS1) to 10.8 MPa (PDMS3), and then decreased down to 4.0 MPa (PDMS5). Autoclave sterilization (AS) increased the storage modulus (sigma) and UTS in all formulations, with the highest increase in UTS exhibited by PDMS5 (218%). PDMS surface hydrophilicity and micro-textures were generally unaffected when exposed to the different chemicals, except for micro-texture changes after immersion in potassium hydroxide and buffered hydrofluoric, nitric, sulfuric, and hydrofluoric acids; and minimal changes in contact angle after immersion in hexane, hydrochloric acid, photoresist developer, and toluene. Oxygen plasma treatment decreased the contact angle of PDMS2 from 109 degrees to 60 degrees. Exposure to tissue culture media resulted in increased PDMS surface element concentrations of nitrogen and oxygen.     

微悬臂梁生物传感器及其在生物医学领域的应用

生物传感器的原理是在传感器中生物分子的相互作用被用作传感反应.生物分子的相互作用,与基于微机电系统(MEMS)技术制造的微悬臂梁平台结合,可以设计出一种功能非常强大的生物传感器.介绍微悬臂梁的工作原理,微梁的读出技术等内容,并在此基础上对微悬臂梁传感器在生物医学领域的应用作了介绍.     

Design of a novel MEMS platform for the biaxial stimulation of living cells

Micromechanical systems are increasingly being used as tools in biological applications, since their characteristic dimensions permit to operate at the same length scale of the structures under investigation. Here, we present a methodology for the design, fabrication and operation of a tool for the assessment of mechanical properties of single cells. In particular, we describe a microsystems platform to study bio-mechanical response of single living cells to in-plane biaxial stretching. The proposed device employs a new linkage design in order to obtain the displacement of the quadrants of a sliced circular plate in mutually-orthogonal directions using just one linear actuator. With this linkage geometry, the whole device has only one degree of freedom. This results in a very predictable and reliable mechanical behaviour, thereby allowing use a simple and easily available control electronics. Results of this study have relevance for the design of a powerful yet simple BioMEMS platform for the characterization of living cells as in-plane bi-axial loading simulated the conditions experienced by cells in vivo more realistically than a uniaxial stretching.     

Nano-opto-mechanical characterization of neuron membrane mechanics under cellular growth and differentiation

We designed and fabricated silicon probe with nanophotonic force sensor to directly stimulate neurons (PC12) and measured its effect on neurite initiation and elongation. A single-layer pitch-variable diffractive nanogratings was fabricated on silicon nitride probe using e-beam lithography, reactive ion etching and wet-etching techniques. The nanogratings consist of flexure folding beams suspended between two parallel cantilevers of known stiffness. The probe displacement, therefore the force, can be measured through grating transmission spectrum. We measured the mechanical membrane characteristics of PC12 cells using the force sensors with displacement range of 10 mum and force sensitivity 8 muN/mum. Young's moduli of 425 +/- 30 Pa are measured with membrane deflection of 1% for PC12 cells cultured on polydimethylsiloxane (PDMS) substrate coated with collagen or laminin in Ham's F-12K medium. In a series of measurements, we have also observed stimulation of directed neurite contraction up to 6 mum on extended probing for a time period of 30 min. This method is applicable to measure central neurons mechanics under subtle tensions for studies on development and morphogenesis. The close synergy between the nano-photonic measurements and neurological verification can improve our understanding of the effect of external conditions on the mechanical properties of cells during growth and differentiation.     

Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery

This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.     

无创胎儿心率检测仪的研制

介绍一种基于32位ARM嵌入式微处理器LPC2290和MEMS微加速度传感器的一种便携、无创的胎儿心率检测仪.通过加速度传感器将胎儿心跳震动信号转化为电信号,经过两级放大电路和滤波陷波电路后通过A/D转换电路将信号送人ARM单片机.利用自相关算法对信号进行处理,最后计算得到胎儿的心率,结果 采用小型液晶进行显示.研究解决了微弱信号的采集和数字信号处理等难题,研制出了一种便携、无创且价格低廉的胎儿心率检测仪,操作简便非常适合家庭使用.     

A high aspect ratio microelectrode array for mapping neural activity in vitro

A novel high-aspect-ratio penetrating microelectrode array was designed and fabricated for the purpose of recording neural activity. The array allows two dimensional recording of 64 sites in vitro with high aspect ratio penetrating electrodes. Traditional surface electrode arrays, although easy to fabricate, do not penetrate to the viable tissue such as central hippocampus slices and thus have a lower signal/noise ratio and lower selectivity than a penetrating array. In the unfolded hippocampus preparation, the CA1-CA3 pyramidal cell layer in the whole unfolded rodent hippocampus preparation is encased by the alveus on one side and the Schaffer tract on the other and requires penetrating electrodes for high signal to noise ratio recording. An array of 64 electrode spikes, each with a target height of 200 μm and diameter of 20 μm, was fabricated in silicon on a transparent glass substrate. The impedance of the individual electrodes was measured to be approximately 1.5 MΩ ± 497 kΩ. The signal to noise ratio was measured and found to be 19.4 ± 3 dB compared to 3.9 ± 0.8 dB S/N for signals obtained with voltage sensitive dye RH414. A mouse unfolded hippocampus preparation was bathed in solution containing 50 micro-molar 4-amino pyridine and a complex two dimensional wave of activity was recorded using the array. These results indicate that this novel penetrating electrode array is able to obtain data superior to that of voltage sensitive dye techniques for broad field two-dimensional neuronal activity recording. When used with the unfolded hippocampus preparation, the combination forms a uniquely capable tool for imaging hippocampal network activity in the entire hippocampus.     

眼底横向显微成像系统的研制及应用

介绍了一套基于MEMS薄膜变形镜的人眼眼底横向显微成像系统。采用37单元MEMS薄膜变形反射镜作为波前校正元件,127微透镜阵列哈特曼夏克（Hartmann—Shack）波前传感器测量波前误差,在用计算机控制薄膜变形镜实现波前误差校正后,开启成像照明光源．用CCD相机记录视网膜图像。模拟眼试验表明．系统能够有效进行像差测量、校正和眼底成像,像差校正后成像质量达到衍射极限。临床试用表明,除少部分眼内比较浑浊的病人外,整个检查过程大部分病人都能够安全、快捷、可靠地进行。