Dual Material Rapid Prototyping Techniques for the Development of Biomedical Devices. Part 2: Secondary Powder Deposition

Polymeric drug delivery devices play an important role in drug administration. However, the current polymeric drug delivery device fabrication methods lack precision. This impairs the quality of the devices, resulting in a decrease in the efficiency and effectiveness of drug delivery. The concept of building parts layer by layer out of powdered raw materials makes selective laser sintering (SLS) a suitable process for fabricating polymeric matrix drug delivery devices. The current SLS process is not capable of processing two or more materials separately. This work explores the possibilities of using SLS to perform a dual material operation by developing two process models. The two processes can then be integrated to form a dual or multimaterial fabrication technique and act as a foundation for future work in multimaterial applications such as polymeric drug delivery device fabrication. Accordingly, two papers are presented. In this paper, Part 2, the emphasis is on a secondary powder deposition method, which is an electrostatic technique based on electrography. Developed toner on the photoconductor is scraped off using mechanical shearing and is deposited using an electrostatic force by electroplating. Results have shown that by reducing the distance between the photoconductor and surface of deposition, the resolution of the printout can be refined. Other important factors include the efficiency of powder removal from the photoconductor, printing speed, and the traversing speed during deposition.     

Dual Material Rapid Prototyping Techniques for the Development of Biomedical Devices. Part 1: Space Creation

Polymeric drug delivery devices play an important role in drug administration. However, the current polymeric drug delivery device fabrication methods lack precision. This impairs the quality of the devices, resulting in a decrease in the efficiency and effectiveness of drug delivery. The concept of building parts layer by layer out of powdered raw materials makes selective laser sintering (SLS) a suitable process for fabricating polymeric matrix drug delivery devices. The current SLS process is not capable of processing two or more materials separately. This work explores the possibilities of SLS per-forming a dual material operation by developing two process models. These two processes can then be integrated to form a dual or expanded multimaterial fabrication technique and act as a foundation for future work in multimaterial applications such as polymeric drug delivery device fabrication. Accord-ingly, two papers are presented. In this paper, Part 1, the focus is on the first process, which is a "space" creation technique in which a "space" is created by varying the density of a first representative material using heat during sintering. Three methods – one based on a vacuum and a place method, and the other two based on two variations of a laser compacting method – were tested. Results have shown that by varying the laser power during sintering, it is possible to create channels in which a second material can be deposited.     

Building Porous Biopolymeric Microstructures for Controlled Drug Delivery Devices Using Selective Laser Sintering

The capability to build parts with predetermined porous microstructure and dense walls using powdered biomaterials makes selective laser sintering (SLS), one of the more flexible rapid prototyping (RP) process, a strong candidate for building biodegradable controlled release drug delivery devices (DDD). The objective is to design a varying-porosity circular disc with outer region being denser acting as diffusion barrier region and inner more porous region acting as drug encapsulation region. This is to achieve a zero-order of release over a desired duration of time in drug administration.A key study in this paper was to determine the influence of critical SLS process parameters namely, laser power, laser scan speed and part bed temperature on dense wall formation and control of the porous microstructure of SLS-fabricated parts built with biomaterials. The physical characteristics of the fabricated devices were investigated through microstructure examination using the scanning electron microscope (SEM). Two biodegradable polymers, namely Polycaprolactone (PCL) and Poly (-L) Lactic Acid (PLLA), were investigated. For PCL varying-porosity disc, the laser power is set at 3 W (inner region) - 4 W (outer region), the scan speed at 5080 mm/s and the part bed temperature at 40°C. For Poly(-L) Lactic Acid (PLLA), the laser power is set at 12 W, the scan speed at 1270 mm/s and the part bed temperature at 60°C. With the set of SLS parameters tabulated for specific polymers, polymeric matrix with specific porosity can be fabricated as drug delivery devices.     

密封系统对低频超声透皮给药的影响

为提高低频超声透皮给药过程中药液渗透率的控制精度,通过有限元计算分析,设计了一款具有密封结构的超声换能器,用以改变低频超声透皮给药系统中的药液压强。基于Franz扩散池的皮肤透皮体外实验的研究(包括人造皮肤与大鼠离体皮肤),获得了密封系统对透皮渗透量变化的影响规律。实验结果表明,超声空化、促渗剂与压强都可以改变药液渗透率,其中超声可以通过空化效应破坏皮肤表层结构进而促进渗透,而压强与超声、促渗剂相互结合则可以起到提高给药渗透精度的作用。提出的密封式超声换能器可通过压强变化初步实现调节低频超声透皮给药精度的目的,为进一步设计可调压强的低频超声给药系统奠定应用基础。     

Modularized simulation for lot delivery time forecast in automatic material handling systems of 300 mm semiconductor manufacturing

The more accurate the forecast is to lot delivery time, the more effective it is in fab scheduling. In fab operations, scheduling is the major impact factor of tools capacity allocation, tools utilization control and bottleneck management. However, there is no effective method to estimate delivery time in 300 mm automatic material handling systems (AMHS) operation. Computer simulations are authentic, but they are either too complex to model fab operations as well as the whole AMHS, or too time-consuming to simulate with a full-scaled fab model. This paper proposes an analytic methodology to estimate the loop-to-loop delivery time for differentiated lots in a 300 mm AMHS environment. Combining simulation and statistics techniques, we develop a modularized simulation method (MSM) for delivery time forecast of priority lots. Numerical experiments based on data from a local 300 mm manufacturing fab are conducted. Simulation demonstrates that the MSM has credible results in estimating lot delivery times. The time differences between MSM and simulation for both priority lots and regular lots are 0.2 s and 0.1 s, respectively. Using the MSM method to forecast AMHS delivery time is a great contribution for streamlining shop floor operations, such as scheduling and dispatching, for eliminating time delays in the 300 mm automatic environment.     

基于MEMS的胃肠道药物释放药丸的研制

介绍用于胃肠道药物定点释放的微型药丸的研制工作,该微型药丸以压力气体致动式工作原理为物理模型,由体外定点控制实现药物定点释放功能.实验表明,研制的微型药丸生物相容性好,释放动作比较可靠,可满足胃肠道定点药物释放的实验研究需要.     

Modularized simulation for lot delivery time forecast in automatic material handling systems of 300?mm semiconductor manufacturing

The more accurate the forecast is to lot delivery time, the more effective it is in fab scheduling. In fab operations, scheduling is the major impact factor of tools capacity allocation, tools utilization control and bottleneck management. However, there is no effective method to estimate delivery time in 300 mm automatic material handling systems (AMHS) operation. Computer simulations are authentic, but they are either too complex to model fab operations as well as the whole AMHS, or too time-consuming to simulate with a full-scaled fab model. This paper proposes an analytic methodology to estimate the loop-to-loop delivery time for differentiated lots in a 300 mm AMHS environment. Combining simulation and statistics techniques, we develop a modularized simulation method (MSM) for delivery time forecast of priority lots. Numerical experiments based on data from a local 300 mm manufacturing fab are conducted. Simulation demonstrates that the MSM has credible results in estimating lot delivery times. The time differences between MSM and simulation for both priority lots and regular lots are 0.2 s and 0.1 s, respectively. Using the MSM method to forecast AMHS delivery time is a great contribution for streamlining shop floor operations, such as scheduling and dispatching, for eliminating time delays in the 300 mm automatic environment.     

Mesenchymal stem cell secretome and nanotechnology: Combining therapeutic strategies

Mesenchymal stem cells (MSC) have pushed the field of stem cell-based therapies by inducing tissue regeneration, immunosuppression, and angiogenesis mainly through vesicles and soluble factors release (paracrine signaling). MSC-extracellular vesicles (MSC-EV) adaptable secretome and homing to injured sites allowed researchers to unlock a new era of cell-free based therapy. In parallel, nanoparticles (NP) have been explored in contributing to transport and drug delivery systems, giving drugs desired physical-chemical properties to exploit cell behavior. However, NPs can be quickly recognized by immune cells and cleared from circulation. In this viewpoint, we explore how combining both therapeutic strategies can improve efficacy and circumvent limitations of both therapies. MSCEV benefit from the potent MSC membrane composition, guiding chemotaxis to tumor sites, a very restricted microenvironment. MSC-EV has low immunogenicity, high stability, long half-life and can explore tissue targeting ligands as a precise drug carry, even across biological barriers. Those properties promote enhanced targeted drug delivery that can be combined with NP, exploring biological membrane production through: 1. direct cell therapy with NP-infused MSC; 2. NP-containing MSC-EV generated by NP-infused MSC; 3. by coating NP in MSC membrane (“MSC NanoGhosts”), allowing precise cargo definition without losing targeting. Therefore, nanotechnology combined with cell-based therapeutic resources can greatly improve targeted drug delivery, improving efficacy and opening a new venue of therapeutic possibilities.     

A genetic algorithm for the inter-cell layout and material handling system design

The traditional optimization processes for the cell system layout (CSL) and material handling system in cellular manufacturing systems (CMSs) were carried out sequentially and separately. The solutions obtained by this means can be far from the total optimum. In this paper, an integrated approach to the problem is proposed that attempts to design CSL and flow path structure simultaneously. The cells in question are assumed to be shape-fixed and have pre-determined pickup/delivery (P/D) stations. A sequence-pair based CSL-generating algorithm allows cells to be placed at any possible position on a continuous floor plan and leads to a corresponding feasible CSL. A grid graph for the CSL is accordingly constructed to provide possible flow paths for the layout. Then, the sum of the traveling distances, determined by the shortest path algorithm, is used to evaluate the CSL. These steps are embedded into a genetic algorithm (GA) that searches the solution space to obtain optimal layouts based on the contour distances between the P/D stations. Computational results demonstrate that the run time required to solve the test problems is quite acceptable given the long-term nature of facility layout decisions. Moreover, a comparison of the computational results with the existing methods indicates that the proposed approach is a viable alternative for effectively generating layout designs for CMS.     

Characterization of human skin impedance after electrical treatment for transdermal drug delivery

A measurement technique based on Electrical Impedance Spectroscopy (EIS) aimed at discriminating electrical effects of the electrical treatment from the electrical characteristics of drug delivery in human skin is presented. The technique turns out to be useful as the first and most crucial step in determining the drug delivered into the skin after electrical treatment. After recalling the background of electrical measurements principle and electrical modeling of biological tissues, the proposed measurement procedure is illustrated. Then, experimental tests of in vivo characterization of the procedure are reported, and the obtained results are discussed.     

全自动整体式毛细管规模液相色谱系统——Waters CapLC~(TM)系统

毛细管液相色谱系统是Waters多年心血的杰作。它利用最先进的光纤技术,使系统可以提供比传统分析规模HPLC高50倍的灵敏度。毛细管水平的流路不仅几乎无死体积,而且可以平稳而高度重现地输出低至1ul/min的流动相,非常适合与质谱检测器的连接。精心的设计与制作,使CapLC系统能够提供优于传统HPLC系统的保留时间重现性与分辨率。系统很适合分析样品量很小的被测物,在疾病目标识别、生化分子和小分子药物的药代动力学研究等方面有广阔的应用前景。 CapLC配以快速高吞吐量进样器和二极管矩阵检测器,是全自动的毛细管LC/MS系统组件     

Calcium chloride linked camel milk derived casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells

Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.     

基于连通概率感知的车联网资源优化技术研究

研究一种自由连通状态下基于车辆速度的多车道连通概率分析模型。该模型主要关注各个路段的连通概率,基于随机过程统计分析理论推导出多车道的道路连通概率。其次,针对单播或多播的端到端的消息分发场景,提出一种基于连通度概率感知的资源优化选择算法。该算法通过考虑车辆速度及方向特征,宏观层次上选择连通度概率高的路段作为数据包转发的路径;微观层次上针对每一路段进行基于邻居信息的多跳广播,快速地将数据包从路段入口传输到路段出口,提高数据分发效率。NS2仿真结果表明,提出的资源优化算法提高了分组转发的有效性,降低了车载网络的分组传输时延。     

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging conftrms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.     

dbSCI: A manually curated database of SARS-CoV-2 inhibitors for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of the ongoing coronavirus disease 2019 (COVID-19) global pandemic. Here, by centralizing published cell-based experiments, clinical trials, and virtual drug screening data from the NCBI PubMed database, we developed a database of SARS-CoV-2 inhibitors for COVID-19, dbSCI, which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments, 81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses. dbSCI provides four major functions: (1) search the drug target or its inhibitor for SARS-CoV-2, (2) browse target/inhibitor information collected from cell experiments, clinical trials, and virtual drug screenings, (3) download, and (4) submit data. Each entry in dbSCI contains 18 types of information, including inhibitor/drug name, targeting protein, mechanism of inhibition, experimental technique, experimental sample type, and reference information. In summary, dbSCI provides a relatively comprehensive, credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.     

Development and in vitro evaluation of a flow-adjustable elastic drug infusion pump

Passive-type drug infusion pumps have several advantages over active-type pumps including a simple drug chamber structure and relatively high operational stability. However, conventional passive-type infusion pumps also have several limitations compared to active ejection pumps, such as a fixed flowrate and monotonic flow pattern. To enhance the clinical feasibility of using passive-type drug infusion pumps, flow readjustment and flow regulation abilities are needed. This paper proposes a new portable elastic drug infusion pump that integrates the advantages of active and passive infusion pumps to improve clinical feasibility. The proposed infusion pump incorporates a passively driven drug chamber and an actively adjusted flow controller, which can adjust and regulate various target flowrates and adjust the flow pattern in accordance with the patient's time-varying physiological status. The proposed infusion pump uses the contraction force of an expanded elastic membrane to extract the drug from the drug chamber for delivery into the patient's body through an outlet catheter. It also utilizes a flow sensor, a flow resistor, and a motor-driven flow restrictor that can monitor the real-time flowrate through the outlet catheter and automatically regulate the actual flow-rate around the target value. Experiments on the proposed system resulted in actual injection rates of 0.49 +/- 0.03 (mean +/- standard deviation), 0.98 +/- 0.03, 1.49 +/- 0.04, and 1.99 +/- 0.03 ml/h when the target injection rate was set to 0.5, 1.0, 1.5, and 2.0 ml/h, respectively. During the entire period of operation from the fully filled state to the totally empty state, an inner-chamber pressure of >100 mmHg was maintained, which shows that the proposed infusion pump can stably maintain its target flowrate as the amount of drug remaining to be injected decreases. It appears that the proposed drug infusion pump can be applied to a wide variety of patient treatments that require short-term, accurate, and stable drug delivery.     

体内胶囊式药物释放微机电系统机构设计研究

提出一种新型的胶囊式药物释放微机电系统的设计模型。该系统以实现药物在人体内定时、定位释放为主要目的。探讨该系统的机构和控制电路设计中的一些关键技术和难点。     

压电驱动微喷雾化器的研制及实验研究

作为一种重要的非注射给药途径，雾化吸入治疗方法具有起效快，药物毒、副作用小等特点，因此被越来越广泛地采用。基于压电驱动喷雾打印机工作基本原理，利用微机加工技术，研制了一种压电驱动微喷雾化器。流量、雾粒的直径和速度是微喷雾化器的重要指标，文中采用相关的仪器分别对这些指标进行了测试。由测试结果可知，微喷雾化器产生的雾粒的直径和速度分布集中，且雾粒直径和速度比较适合于雾化吸入治疗，可能成为一种重要的雾化吸入治疗装置。     

基于Android的物流派送信息系统的实现

该文综合运用智能手机触摸屏、蓝牙、摄像头和GSM功能,开发了一种基于Android系统的物流派送信息系统应用软件。软件包括信息录入APP和信息发送APP两部分,信息录入APP用来录入发件人和收件人信息,并将信息通过手机蓝牙传送给蓝牙打印机打印出二维码;信息发送APP用来启动手机摄像头识别二维码,并自动发送信息或者拨打电话给收件人。测试结果表明,该软件操作方便,运行稳定,可以有效提高物流派送效率。     

Current engineering and clinical aspects of needle-free injectors: A review

Needle-free injectors can be used to achieve non-invasive drug delivery by impregnating biological barriers. They are considered as the future of drug delivery and therapeutic applications. The history of needle-free injectors dates back to the 1940s and these devices have been constantly evolving since then. Their operating principles and applications have been improved over the years. Herein, we review the current engineering mechanisms and clinical aspects of needle-free microjet injectors. The present study focuses on using engineering approaches to deal with various factors that affect the penetration and dispersion characteristics of the microjet.