Holger Neubert

Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs

In vivo, bone formation is a complex, tightly regulated process, influenced by multiple biochemical and physical factors. To develop a vital bone tissue engineering construct, all of these individual components have to be considered and integrated to gain an in vivo-like stimulation of target cells. The purpose of the present studies was to investigate the synergistic role of defined biochemical and physical microenvironments with respect to osteogenic differentiation of human mesenchymal stem cells (MSCs). Biochemical microenvironments have been designed using artificial extracellular matrices (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya), formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL) scaffolds. As part of the physical microenvironment, cells were exposed to pulsed electric fields via transformer-like coupling (TC). Results showed that aECM containing sHya enhanced osteogenic differentiation represented by increases in ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX-2, ALP, OPN). Electric field stimulation alone did not influence cell proliferation, but osteogenic differentiation was enhanced if osteogenic supplements were provided, showing synergistic effects by the combination of sHya and electric fields. These results will improve the understanding of bone regeneration processes and support the development of effective tissue engineered bone constructs.

Thick Film Accelerometers in LTCC Technology—Design Optimization, Fabrication, and Characterization

Diaphragms and beams for force and pressure sensors, e.g., are state of the art in mechanical elements of MEMS in LTCC technology. These elements sustain small strains and small deformations under load. A number of sensor and actuator applications, however, require movable elements that allow higher deformations while the local strains are still low. Springs, accelerometers, actuators, positioners, and valves are examples of such applications. For an accelerometer we developed an approach fabricate leaf springs, integrated into the LTCC technology. The working principle of the accelerometer is based on a seismic mass disposed on two parallel leaf springs that carry piezoresistors connected such that they form a measuring bridge. In the first design optimization step, we used an FEA model for finding an optimized design meeting our sensitivity requirements, inclusiding resonance frequency. In the second step, we made a tolerance analysis that calculates the probability distributions of functional variables...

Actuators to be integrated in Low Temperature Cofired Ceramics (LTCC) microfluidic systems

LTCC technology has recently been used for microfluidic elements, e.g. channels, cavities and other passive fluidic components. However, microfluidic systems having enhanced functionality, e.g. differential pressure sensors, dosing devices and pumps, require active components that include electrically driven actuators. Up to now, only piezo-cantilevers, electromagnetic and thermo-pneumatic actuators have been engineered for the LTCC integration [1–4]. Due to their specific properties, they are not suitable for all applications that require an actuator. Therefore, a review on actuators capable of being integrated in LTCC is given. On the one hand, the actuators are compared according to their functional properties, e.g. stroke and switching energy, so that actuators can be figured out that fulfil the requirements of a microfluidic system to be designed. On the other hand, the technological challenges to be coped with in the integration of the actuators are listed. Both the functional properties of an actuator and the possibility to integrate it decide on the suitability for a specific application. Using our evaluation method, we introduced actuators for two different microfluidic applications, a piezo-electrically controlled throttle for a DMFC (Direct Methanol Fuel Cell) application and an electrostatic valve for a differential pressure sensor.

A Novel Approach for In Vitro Studies Applying Electrical Fields to Cell Cultures by Transformer-Like Coupling

The purpose of this study was to develop a new apparatus for in vitro studies applying low frequency electrical fields to cells without interfering side effects like biochemical reactions or magnetic fields which occur in currently available systems. We developed a non-invasive method by means of the principle of transformer-like coupling where the magnetic field is concentrated in a toroid and, therefore, does not affect the cell culture. Next to an extensive characterization of the electrical field parameters, initial cell culture studies have focused on examining the response of bone marrow-derived human mesenchymal stem cells (MSCs) to pulsed electrical fields. While no significant differences in the proliferation of human MSCs could be detected, significant increases in ALP activity as well as in gene expression of other osteogenic markers were observed. The results indicate that transformer-like coupled electrical fields can be used to influence osteogenic differentiation of human MSCs in vitro and can pose a useful tool in understanding the influence of electrical fields on the cellular and molecular level.

A Simple Phenomenological Model for Magnetic Shape Memory Actuators

This paper presents a new phenomenological model for magnetic shape memory (MSM) alloy actuators. The model was implemented as a lumped element for multi-domain network models using the Modelica language. These network models are rapidly computed and are therefore well suited for MSM-based actuator design and optimization. The proposed MSM model accounts for the 2-D hysteresis of the magnetic field-induced strain as a function of both the applied magnetic flux density and the compressive stress. An extended Tellinen hysteresis formulation was utilized to compute the mechanical strain of the MSM material from measured upper and lower limiting hysteresis surfaces. Two alternative approaches for the computation of the lumped element have been implemented. The first method uses hyperbolic shape functions to approximate the limiting hysteresis surfaces and offers a good balance of simulation accuracy, numerical stability, computational speed, and ease of parameter identification. The second method uses 2-D lookup tables for direct interpolation of the measured limiting hysteresis surfaces, which leads to higher accuracy. Finally, a test case having simultaneously varying compressive stress and magnetic flux density was utilized to experimentally validate both methods. Sufficient agreement between the simulated and measured strain of the sample was observed.

Low temperature cofired ceramics (LTCC)-based miniaturized load cells

This work presents miniaturized piezoresistive load cells in LTCC for low force ranges. Compared to former investigations on this area we designed the load cells according to commercial products. We used a freestanding cartwheel structure with co-fired piezoresistive resistors as deformable bodies which combines both: high sensitivity and a high robustness against shear forces. The designed packaging allows the sensing of compressive and tensile forces for different ranges (2 N, 5 N and 10 N) and is characterized by a high miniaturization. We developed an analytical model to design the cartwheel structures and to predict the expected characteristics. To increase the repeatability and the reliability we studied different fabrication techniques to reduce cracks, delaminations and sagging. The sensor elements were fabricated in the standard LTCC-technology on GT 951. The fabricated load cells were characterized between 25 °C and 80 °C regarding relevant parameters. The results show a good match to the theoretically calculated values.

A high-speed interferometric dilatometer based on the inductive heating of a specimen

A high-speed dilatometer has been designed for high precision measurements of the thermal expansion/contraction of solid samples. The length of the specimens is measured using a differential interference method with a resolution of 0.3 nm. The temperature is controlled by induction heating and gas cooling. The maximum heating rate is about 100 K s?1 and the maximum cooling rate is 50 K s?1. The system enables measurements under different gas atmospheres, including oxygen, up to temperatures of 1600 ?C.

Highly-sensitive flow sensor in LTCC

In this work we present a miniaturized gas flow sensor in Low Temperature Co-fired Ceramics (LTCC) based on hot-wire-anemometry. The newly developed LTCC fabrication process makes it possible to produce very thin freestanding heating structures within the ceramic showing a smaller power loss than actual state of art solutions. The new technological approach is the use of fugitive sacrificial material based on graphite preventing the free standing structures within the channel from sagging during the lamination and sintering steps. Furthermore we analyzed the influences of the sensor dimensions and the working temperature on the sensor performance in an analytic model and in a two dimensional Finite Element Model (FEM). At last the results of modeling and measurement are presented and discussed.

Uncertainty-Based Design Optimization of MEMS/NEMS

In designing micro-electromechanical systems (MEMS), model-based design and design optimization is inevitable. This is due to the complexity of the working principles and the manufacturing technology associated with high initial costs for experimental investigations. Uncertainty-based design optimization enables stochastic variables, such as scattering material properties, manufacturing tolerances, stochastic time dependent loads, aging, or wear, to be considered in the design. In this chapter, the fundamental concept of reliability or failure probability is introduced and probabilistic approximation and simulation methods are described. These methods are used for robust design optimization (RDO) and reliability-based design optimization (RBDO) as well. Applications and examples for of both approaches are also provided.

Optimization of an electromagnetic linear actuator using a network and a finite element model

Model based design optimization leads to robust solutions only if the statistical deviations of design, load and ambient parameters from nominal values are considered. We describe an optimization methodology that involves these deviations as stochastic variables for an exemplary electromagnetic actuator used to drive a Braille printer. A combined model simulates the dynamic behavior of the actuator and its non-linear load. It consists of a dynamic network model and a stationary magnetic finite element (FE) model. The network model utilizes lookup tables of the magnetic force and the flux linkage computed by the FE model. After a sensitivity analysis using design of experiment (DoE) methods and a nominal optimization based on gradient methods, a robust design optimization is performed. Selected design variables are involved in form of their density functions. In order to reduce the computational effort we use response surfaces instead of the combined system model obtained in all stochastic analysis steps. Thus, Monte-Carlo simulations can be applied. As a result we found an optimum system design meeting our requirements with regard to function and reliability.