An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD³ (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD³ provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD³ are proposed. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. N. M. Elman and H. L. Ho Duc contributed equally to this work.     

The relationship between gastrointestinal symptom attribution,bothersomeness, and antiretroviral adherence among adults with HIV

Patients who attribute their symptoms to HIV medications, rather than disease, may be prone to switching antiretrovirals (ARVs) and experience poor retention/adherence to care. Gastrointestinal (GI) symptoms (e.g., nausea/vomiting) are often experienced as a side effect of ARVs, but little is known about the relationship of symptom attribution and bothersomeness to adherence. We hypothesized that attribution of a GI symptom to ARVs is associated with a reduction in adherence, and that this relationship is moderated by the bothersomeness of the symptom. Data for our analysis come from the pre-randomization enrollment period of a larger study testing an adherence improvement intervention. Analyses revealed that patients with diarrhea who attributed the symptom to ARVs (compared to those who did not) had significantly worse adherence. We did not find a significant moderating effect of bothersomeness on this relationship. Incorporating patient beliefs about causes of symptoms into clinical care may contribute to improved symptom and medication management, and better adherence.     

A Fast and Implantation-Free Sample Production Method for Large Scale Electron-Transparent Metallic Samples Destined for MEMS-Based In Situ S/TEM Experiments

Microelectromechanical systems (MEMS) are currently supporting ground-breaking basic research in materials science and metallurgy as they allow in situ experiments on materials at the nanoscale within electron microscopes in a wide variety of different conditions such as extreme materials dynamics under ultrafast heating and quenching rates as well as in complex electro-chemical environments. Electron-transparent sample preparation for MEMS e-chips remains a challenge for this technology as the existing methodologies can introduce contaminants, thus disrupting the experiments and the analysis of results. Herein we introduce a methodology for simple and fast electron-transparent sample preparation for MEMS e-chips without significant contamination. The quality of the samples as well as their performance during a MEMS e-chip experiment in situ within an electron microscope are evaluated during a heat treatment of a crossover AlMgZn(Cu) alloy.     

Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynaptic cell. Our in vivo experiments on the embryonic Drosophila nervous system show that vesicle clustering at the neuromuscular presynaptic terminal depends on mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored when mechanical tension is applied to the severed end of the axon. Clustering increases when intact axons are stretched mechanically by pulling the postsynaptic muscle. Using micro mechanical force sensors, we find that embryonic axons that have formed neuromuscular junctions maintain a rest tension of ≈1 nanonewton. If the rest tension is perturbed mechanically, axons restore the rest tension either by relaxing or by contracting over a period of ≈15 min. Our results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation and synaptic plasticity.     

基于MEMS的微型泵技术研究

基于硅微结构的微流体控制系统--微型泵,是微机电系统(MEMS)中的一个重要分支,可广泛用于生物、医学、化工、电子、航空等领域.综述了国内外微流体控制系统中微泵技术的研究现状,介绍了几种常用微型泵的工作结构原理,并讨论现有技术中存在的一些问题,以及提出了尝试解决的办法.     

Automatic microfluidic platform for cell separation and nucleus collection

This study reports a new biochip capable of cell separation and nucleus collection utilizing dielectrophoresis (DEP) forces in a microfluidic system comprising of micropumps and microvalves, operating in an automatic format. DEP forces operated at a low voltage (15 V_p–p) and at a specific frequency (16 MHz) can be used to separate cells in a continuous flow, which can be subsequently collected. In order to transport the cell samples continuously, a serpentine-shape (S-shape) pneumatic micropump device was constructed onto the chip device to drive the samples flow through the microchannel, which was activated by the pressurized air injection. The mixed cell samples were first injected into an inlet reservoir and driven through the DEP electrodes to separate specific samples. Finally, separated cell samples were collected individually in two outlet reservoirs controlled by microvalves. With the same operation principle, the nucleus of the specific cells can be collected after the cell lysis procedure. The pumping rate of the micropump was measured to be 39.8 μl/min at a pressure of 25 psi and a driving frequency of 28 Hz. For the cell separation process, the initial flow rate was 3 μl/min provided by the micropump. A throughput of 240 cells/min can be obtained by using the developed device. The DEP electrode array, microchannels, micropumps and microvalves are integrated on a microfluidic chip using micro-electro-mechanical-systems (MEMS) technology to perform several crucial procedures including cell transportation, separation and collection. The dimensions of the integrated chip device were measured to be 6 × 7 cm. By integrating an S-shape pump and pneumatic microvalves, different cells are automatically transported in the microchannel, separated by the DEP forces, and finally sorted to specific chambers. Experimental data show that viable and non-viable cells (human lung cancer cell, A549-luc-C8) can be successfully separated and collected using the developed microfluidic platform. The separation accuracy, depending on the DEP operating mode used, of the viable and non-viable cells are measured to be 84 and 81%, respectively. In addition, after cell lysis, the nucleus can be also collected using a similar scheme. The developed automatic microfluidic platform is useful for extracting nuclear proteins from living cells. The extracted nuclear proteins are ready for nuclear binding assays or the study of nuclear proteins.     

Development of Novel Glucose Sensing Fluids with Potential Application to Microelectromechanical Systems-Based Continuous Glucose Monitoring

Background

We have previously presented a microelectromechanical systems (MEMS) viscometric sensor for continuous glucose monitoring. The sensing fluid used therein was based on protein concanavalin A, which is known to have significant drawbacks, such as immunotoxicity and instability. To address this issue, a stable, biocompatible polymeric sensing fluid has been developed.

Methods

In the polymeric sensing system, glucose reversibly formed strong ester bonds with the phenylboronic acid moiety on the poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA) polymer backbone, resulting in cross-linking of the copolymers and an increase in the solution viscosity. The copolymers were synthesized via classic free radical copolymerization processes. The viscosity of the PAA-ran-PAAPBA, dissolved in phosphate-buffered saline buffer and in the presence of glucose at physiologically relevant concentrations, was measured by an Ubbelodhe viscometer and a prototype MEMS viscometric device.

Results

Experimental results showed that the polymer molecular weight and composition depended on the solvent quantity, while the sensing fluid viscosity was determined by the polymer molecular weight and percentage composition of PAAPBA. The study of the temperature effect on viscosity showed that the polymer sensed glucose effectively under physiological conditions, although the high temperature lowered its sensitivity. Through proper adjustment of these parameters, a distinctive viscosity increase was observed when the glucose concentration increased from 0 to 450 mg/dl, which was detectable by our prototype MEMS device.

Conclusions

We have successfully developed a stable, biocompatible polymeric system for the sensitive detection of glucose. MEMS experiments demonstrated that the sensing fluid was able to sense glucose at different concentrations. This sensing system can potentially enable highly reliable, continuous monitoring of glucose in interstitial fluid from subcutaneous tissue.     

用于人体药物吸收研究的定点释放药丸系统研制

定点释放药丸系统是一种基于微型机械电子系统(MEMs)的工程药丸，无创地实现了消化道内定点药物释放。人体药物吸收(Human Drug Absorption，HDA)研究是新药开发过程中获得药物吸收路线图的重要手段，定点释放药丸系统是HDA研究的重要工具。本研究开发了一种新型的定点释放药丸系统，并开发了基于磁标记跟踪技术的定位跟踪系统，该定点释放药丸系统具有使用方便、效率高、适应多种药物剂型的优点，该系统也为中药药理学研究提供了一种新的手段，具有良好的应用前景。     

基于电热型扫描微镜的微型双光子显微镜探头设计

双光子荧光显微镜的微型化对在体脑部神经活动研究和体内组织病理状态检测具有非常重要意义。本文设计了一种基于电热型扫描微镜的微型化双光子荧光显微镜探头,其微镜设计采用反向串联双S型双层材料结构,通过对微镜四个侧面执行器分别施加周期信号,实现了±3.5°的扫描范围;其光学设计是通过单模光纤导入800 nm飞秒激光,激光经微镜扫描,由光学系统聚焦作用于生物样品,激发样品产生荧光,荧光信号通过采集光路汇集并耦合到多模光纤输出,最后通过显微镜的图像采集系统成像。探头尺寸为26 mm(L)×12 mm(W)×8 mm(H),重量为5.6 g。利用该显微镜探头,对含有不同尺寸凹槽的微结构进行了成像测试,其结果表明,其扫描成像的范围可以实现150μm×150μm,横向分辨率可达到5μm;利用该探头对荧光染色小鼠肾脏冷冻切片进行的成像测试,成功得到了双光子二维荧光图像。基于本装置以及进一步的改进,将有助于构建便携式双光子荧光显微镜,置于活体动物头部,在体进行脑部神经活动研究。