Frank Goldschmidtböing

A generic analytical model for micro-diaphragm pumps with active valves

We present a fully analytical model for micro-diaphragm pumps with active valves, based on the peristaltic working principle. Our model is suited for very fast as well as for very slow actuation mechanisms. Therefore it can be applied to a variety of actuation principles, e.g. piezoelectric, pneumatic, thermo-pneumatic or pre-stressed shape memory actuation. We show that the dynamics of this kind of micropump can be fully described by a lumped element approach taking only the mechanical behaviour of the diaphragms and the viscous losses at the valves into account. The full flow versus frequency and backpressure characteristic is derived. Our model is capable of predicting the maximum achievable flow rate and the maximum sustainable backpressure of micro-diaphragm pumps with active valves. Different modes of operation, which are distinguished by the speed of the actuation mechanism, the pressure history inside the pump and the applied driving scheme, are identified. We show that micro-diaphragm pumps with active valves generally suffer from a linear dependence of the flow rate on the applied backpressure. This fact, which is already known from micropumps with passive valves, is remarkable, because it is in contradiction to the characteristics of macroscopic peristaltic pumps. A set of design rules for the dimensioning of the valves in dependence on the actuation force and the desired hydrodynamic characteristics (maximum flow rate and maximum sustainable backpressure) are derived. Our theoretical results are proven by experimental results of our piezoelectrically actuated micropump. A maximum flow rate of 1.4 ml min−1 and a maximum sustainable backpressure of 40 kPa were achieved.

Pressure-Independent Micropump with Piezoelectric Valves for Low Flow Drug Delivery Systems

We present - for the first time - a novel design of a micropump which enables a backpressure-independent flow rate up to 20 kPa within the low flow regime required for drug delivery systems. Our concept, based on two piezoelectrically actuated diaphragms, allows an accurate dosing in the range of 1 - 50 µ l/min with freely programmable release profiles and offers the potential to minimize chip size and power consumption in comparison to 3-actuator peristaltic micropumps. The stroke volume is adjustable between 50 - 200 nl by means of voltage control which enables a high resolution volumetric dosing. Within the relevant frequency range below 2 Hz the flow rate is proportional to the frequency. Our design also excels in its comparably simple and robust 2-layer fabrication process.

Piezoelectric microactuators in polymer-composite technology

This paper describes process development, fabrication and testing of piezoelectric micro actuators based on a novel polymer-composite technology. Fabrication is done by using segmented silicone molds for the insert-casting of piezoactuators into polymeric material. Furthermore, a simulation model was developed to forecast the principal behavior of the micro actuators and to perform an optimization of the stroke. Based on these results, a number of test structures were fabricated. Finally the displacement was measured and compared to the simulation model.

German Artificial Sphincter System-GASS

No highly integrated sphincter prosthesis for therapy of anal incontinence exists. Therefore, this trial was performed to develope a novel artificial sphincter: the German Artificial Sphincter System „GASS“. This device combine the fluid reservoir, the occlusion cuff and micropump to a highly integrated device. The GASS is completely manufactured of polyurethane. The micropump is based on piezo-technology. Threshold of continence and the pressure-volume relationship of the cuff prosthesis were evaluated in an in vitro simulator using isolated porcine bowel segments and isolated anal canals. Minimal filling volumes between 6.5 and 7 cc could maintain continence for liquids against high luminal pressures. The high pressure zone of the occlusion cuffs reached only intraluminal pressure values between 36-76 mm Hg, indicating a little risk of ischaemie injury of the bowel respectively the anal canal. In summery, an integrated, patented and functionable sphincter device, easy to implant, could be realized.

Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug

The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

Design, Characterization and Sensitivity Analysis of a Piezoelectric Ceramic/Metal Composite Transducer

This article presents experimental characterization and numerical simulation techniques used to create large amplitude and high frequency surface waves with the help of a metal/ceramic composite transducer array. Four piezoelectric bimorph transducers are cascaded and operated in a nonlinear regime, creating broad band resonant vibrations. The used metallic plate itself resembles a movable wall which can align perfectly with an airfoil surface. A phase-shifted operation of the actuators results in local displacements that generate a surface wave in the boundary layer for an active turbulence control application. The primary focus of this article is actuator design and a systematic parameter variation experiment which helped optimize its nonlinear dynamics. Finite Element Model (FEM) simulations were performed for different design variants, with a primary focus in particular on the minimization of bending stress seen directly on the piezo elements while achieving the highest possible deflection of the vibrating metallic plate. Large output force and a small yield stress (leading to a relatively small output stoke) are characteristics intrinsic to the stiff piezo-ceramics. Optimized piezo thickness and its spatial distribution on the bending surface resulted in an efficient stress management within the bimorph design. Thus, our proposed resonant transduction array achieved surface vibrations with a maximum peak-to-peak amplitude of 500 μm in a frequency range around 1200 Hz.

A New Concept of a Drug Delivery System with Improved Precision and Patient Safety Features

This paper presents a novel dosing concept for drug delivery based on a peristaltic piezo-electrically actuated micro membrane pump. The design of the silicon micropump itself is straight-forward, using two piezoelectrically actuated membrane valves as inlet and outlet, and a pump chamber with a piezoelectrically actuated pump membrane in-between. To achieve a precise dosing, this micropump is used to fill a metering unit placed at its outlet. In the final design this metering unit will be made from a piezoelectrically actuated inlet valve, a storage chamber with an elastic cover membrane and a piezoelectrically actuated outlet valve, which are connected in series. During a dosing cycle the metering unit is used to adjust the drug volume to be dispensed before delivery and to control the actually dispensed volume. To simulate the new drug delivery concept, a lumped parameter model has been developed to find the decisive design parameters. With the knowledge taken from the model a drug delivery system is designed that includes a silicon micro pump and, in a first step, a silicon chip with the storage chamber and two commercial microvalves as a metering unit. The lumped parameter model is capable to simulate the maximum flow, the frequency response created by the micropump, and also the delivered volume of the drug delivery system.

Virtuelle Messgeräte: Definition und Stand der Entwicklung (Virtual Measuring Instruments: Definition and Development Status)

Die Mikro- und Nanotechnologie gehört zu den Schlüsseltechnologien des 21. Jahrhunderts mit hohen Wachstumsprognosen, wie auch die im Auftrag des BMBF durchgeführte Studie “Nanotechnologie als wirtschaftlicher Wachstumsmarkt” von 2004 ausführlich darstellt. Aus diesem Trend resultiert ein steigender Bedarf an Messsystemen, die Nanostrukturen prozessnah bzw. im Fertigungsprozess charakterisieren können. Virtuelle Messgeräte liefern Erkenntnisse zur Entwicklung neuartiger Messsysteme, Analyse und Optimierung bestehender Verfahren sowie die Bestimmung der Messunsicherheit und modellbasierten Korrektur systematischer Fehler. Der virtuelle Messprozess umfasst neben dem Messmittel auch die Probe und die Wechselwirkungen zwischen beiden. In diesem Beitrag werden virtuelle Messgeräte vorgestellt sowie deren Anwendung diskutiert. Micro- and nanotechnology experienced a high economic growth in recent years. This yields in a growing demand for measuring instruments which are closely linked to the production process. Virtual measuring instruments provide knowledge for the development of new systems, the analysis and optimization of established devices as well as the determination of the uncertainty in measurement. The virtual measuring process consists of the measuring instrument, the sample, and the interaction between both. In this article examples of current developments of virtual instruments are presented and their way of utilization is discussed.

Stress-Free Bonding Technology with Pyrex for Highly Integrated 3D Fluidic Microsystems

In this article, a novel Pyrex reflow bonding technology is introduced which bonds two functional units made of silicon via a Pyrex reflow bonding process. The practical application demonstrated here is a precision dosing system that uses a mechanically actuated membrane micropump which includes passive membranes for fluid metering. To enable proper functioning after full integration, a technique for device assembly must be established which does not introduce additional stress into the system, but fulfills all other requirements, like pressure tolerance and chemical stability. This is achieved with a stress-free thermal bonding principle to bond Pyrex to silicon in a five-layer stack: after alignment, the silicon-Pyrex-silicon stack is heated to 730 °C. Above the glass transition temperature of 525 °C Pyrex exhibits viscoelastic behavior. This allows the glass layer to come into close mechanical contact with the upper and lower silicon layers. The high temperature and the close contact promotes the formation of a stable and reliable Si-O-Si bond, without introducing mechanical stress into the system, and without deformation upon cooling due to thermal mismatch.

A miniaturized pressure independent drug delivery system for metronomic cancer therapy

We present the results of our currently completed project “Active Microports”. A miniaturized drug delivery system for metronomic cancer therapy was developed. It has a total weight of only 36g and is able to deliver flowrates between zero and 6 µl/min virtually independent of the backpressure for pressures up to 30 kPa. The feasibility of the approach was demonstrated by a trial on metronomic cancer therapy with doxorubicin on a rat prostate tumor model.