Biocatalysis has become an empowering technology in modern organic synthesis. The use of enzymes for chemical transformations often grants unparalleled chemo-, regio- and stereoselectivity and enables transformations that would be unachievable using conventional chemical methods. In this regard and inspired by nature, recent years have witnessed a growing interest in the design of multi-step enzyme cascade reactions by combining several enzyme-catalyzed steps in one reactor (one pot) without intermediate purification steps、
Microfluidic devices provide an ideal reaction vessel for multi-step biocatalytic cascades in flow, as reactions in microsystems can be effectively compartmentalized, reaction and separation steps can be independently controlled, and throughput can be increased via parallelization. Additional advantages of microfluidics such as much higher surface-area-to-volume ratios, and tremendously increased mass and heat transfer rates. To perform biocatalytic cascades in microfluidic systems, individual enzyme catalysts are commonly immobilized in either separate but connected microsystems or neighboring compartments on the same microsystem. Hence, reaction steps of a cascade are spatially separated, but still connected in flow.
Endothelial cells lining the blood vessel walls are known to change their morphology, function and gene expression according to the mechanobiological stimuli they are experiencing. Such stimuli include shear stress caused by blood flow and the stiffness of the underlying extracellular matrix. However, little is known about the cumulative effects of mechanobiological stimuli over endothelial cell behavior, and even less is known about their role in bacterial infection. In this project, we aim to investigate the mechanobiology of the vascular endothelium in relation to the dissemination of the Lyme disease pathogen, Borrelia burgdoferi, on an organ-on-chip (OoC) platform. The OoC platform will allow precise control over the biomechanical microenvironment endothelial cells are subjected to and will be equipped with integrated sensors for the evaluation of important parameters such as endothelial barrier integrity. Ultimate goal is a correlation between endothelial biomechanics and the mechanisms of Borrelia burgdorferi dissemination.
The human small intestine is an integral interface with the environment, although inside the body. With an area of approximately 30 m2, it is 15 times larger than the area of our skin and it performs several complicated functions including digestion, absorption and nutrients, while providing a basis for intestinal flora and barrier function against pathogens. In this project, we generate small intestine-like structures with the help of a cell-stretching platform. Using cyclic stretching, we stimulate the formation of 3D villi-like structures, which resemble the architecture of the human intestine. The biomimetic nature of this platform allows the generation of organotypic tissue models that are more similar to their in vivo counterparts compared to conventional cell cultures. Therefore, this 3D cell model promises a better transferability of the findings to the human situation without the need for animal models. Using this platform, we aim to study the relation between biomechanics and infection with pathogens (e.g., Listeria monocytogenes and SARS-CoV-2), as well as to test the uptake of orally administered drugs.
To combat infectious diseases, it is important to understand how host cells interact with bacterial pathogens in a milieu dominated by chemical as well as mechanical signals. Currently available biomimetic cell culture platforms which account for the mechanical stretch and fluidic flow are limited in their applicability for comprehensive biomechanical infection assays.
The aim of this project is to develop a platform which is then applied in infection assays of Listeria Monocytogenes (LM) bacteria. This platform has to allow for:
combination of cell stretching / shear flow
multiple stretch patterns
access from top for infection assays
live-cell time-lapse microscopy
conduction of cellular biomechanical measurements
The project is a collaboration with the University of Tübingen, which is applying the system in bio-chemo-mechanical infection studies.
At IMT, we apply 3D-printing and PDMS molding/spinning techniques to manufacture cell culture systems with stretchable membranes. We characterize the developed systems by applying the finite elment method to model the strain in the membrane and validate the outcomes by microscopy and image correlation.
Microfluidic organ-on-chip (OoC) platforms are increasingly utilized in biomedical research and development as a replacement for traditional static cell cultures and animal experiments. In this project, we aim to develop a miniaturized electrical impedance tomographer (EIT) and integrate it into an organ-on-chip platform for label-free cell and tissue characterization. EIT is a commonly used, non-invasive, and radiation-free type of medical imaging. Beyond the well-known medical applications, EIT can be used to reconstruct the impedance distribution of samples placed within an electrode array, given variations in conductivity across the sample. The resolution of the acquired “electrical images” depends on many parameters such as the size of the sampling volume, the geometry of the electrode array, the parameters used during measurement and the algorithms used for image reconstruction. In addition to the standard regularization technique, the reconstruction of the "electrical image" can be improved by using deep learning methods to achieve high resolution and fast computation for real-time imaging. Our aim is to reduce the sampling volume through miniaturization, and optimize all other important parameters in order to acquire impedance maps with cellular resolution (10-20 µm). This will allow us to observe localized events taking place across cellular monolayers cultured under biomimetic conditions.
Project period: 06/2023 -
Funding organization: SMART BIOTECS - Land Niedersachsen
With the BM=x^3 project, we not only want to bring professional training in micro- & nanotechnology to the forefront of society, but also bring the type of training up to date. More flexible and dynamic learning and further education are in the focus here. For this we want to create a new platform to connect the present and the virtual world.
Project period: 2021-2024
Funding organization: Bundesinstitut für Berufsbildung
By combining controllable microfluidic nanoparticle generation from the Institute for Microtechnology (IMT) at the TU Braunschweig with the DLS System developed at the Fraunhofer Institute for Microtechnology and Microsystems (IMM) in Mainz, a feedback-regulated nanoparticle reactor is to be realized with which the size, size distribution and shape of the generated particles can be precisely controlled and can be sure about the stability of the process for a long time. A new type of microfluidic precipitation system is to be developed on the basis of existing prototypes of microfluidic systems from IMT, which, together with the existing flowDLS system from Fraunhofer IMM (IMM), allows direct online measurement of the generated nanoparticles in the microfluidic channel. The application partner ConSenxus GmbH comes from the field of instrument engineering and has decades of expertise in the field of particle analysis methods. Also, ConSenxus has useful contacts as well as the necessary special knowledge to adapt the system to the needs of potential users
The aim of the Research Unit FOR3022 is to gain a profound understanding of an integrated Structural Health Monitoring in Fiber Metal Laminates using guided ultrasonic waves. The group at IMT investigates microfabricated and structure integrable acceleration sensors, which monitor the adhesive boundary layer within fiber metal laminates. Using glass and silicon as sensor materials, the acoustic impedance of the sensor resembles that of the structure, yielding functional compliance.
The overarching goal of the HomeoHirn consortium is to explore the homeostasis of neural and glial cells in an interdisciplinary network of neuroscience, systems biology, chemistry, and engineering sciences such as mechanical and electrical engineering.
This subproject of the HomeoHirn consortium aims to develop a multi-electrode array platform with a microfluidic chamber for subcellular analysis of neuronal responses. The robust and transparent platform enables the combination of electrophysiological recordings and optogenetic experiments with single-cell resolution using local stimulation of cell-specific structures by light-emitting diodes (LEDs) or local chemical gradients (two-photon uncaging of glutamate).
In Niedersachsen, structures have been established in the last few years in which scientific research groups have been working on ways to replace and save laboratory animals in research. In particular, through a joint funding program (R2N) the development of alternative systems for animal model-based research was initiated. From this consortium, complementary groups have emerged that, together with partly new partners of the network alternative models for basic research on the digestive tract (intestine, oral mucosa) and respiratory tract. Thus the "Replace" idea is to be primarily implemented in the requested funding. Through the humanized systems, an optimal transferability of the results into clinical and commercial clinical and commercial use will be ensured.
The aim of this project is to investigate a multifunctional bondline, which is capable of joining two adherents made from carbon fiber reinforced polymer. This is intended to improve the reliability of bonds between lightweight components. The specially designed bondline shall slow or stop crack propagation and monitor its own structural health. Therefore integrated thin foil sensors, fabricated by means of lithography measure the gradient of stress inside the bond without degrading its mechanical properties. Metallic thin film sensors are structured directly on a PVDF substrate, which becomes a part of the crack stopping mechanism when embedded into the carbon fiber matrix. The epoxy resin, which is carrying the major portion of the loads inside the bond, remains completely undisturbed. With suitable algorithms the sensor signals shall be analysed to reliably detect cracks within the bondline. This new way of integrating sensors will lead to a higher level of structural compliance in comparison to sensors being integrated into the epoxy resin layer.
The aim of the study is to develop a novel miniature device – termed NeuroExaminer – by structured microfabrication of glass that enables a stable and highly reproducible positioning of both zebrafish larvae and juveniles within a system with perfected optical properties for whole brain light-sheet microscopy at the subsecond time-scale. Furthermore, the NeuroExaminer will contain microchannels for precisely controlled compound application with subsecond resolution and steep concentration gradient formation.
This will allow to reveal the pharmacokinetics and neuromodulatory functions of any water soluble compound. In the course of the project we will develop a proof of concept by using the NeuroExaminer to investigate brain-wide alterations induced by two different psychostimulant substances through continuously monitoring neuronal activity at cellular resolution over at least one hour. This will demonstrate that the NeuroExaminer is a powerful novel instrument to reveal the specific neural activity of drugs, including their lag time until neuromodulation is achieved together with circuit activation or repression in a time-dependent manner.
The aim of this project is to detect Nanoparticles in a deformable microchannel using the electric current changing. To do that a microchannel will be fabricated using the silicon dry etching method and the gold electrodes will be placed on top the microchannel by the help of the sputtering technique. A thin PDMS layer will be then settled as an elastic membrane on top of the silicon microchannel together with the electrodes which the actuator will act on. The SMA actuator on the top, then, can change the cross section of the channel by moving the PDMS membrane. The whole system will be then connected to the electronic setup through the electrodes and the fluid flow containing the nanoparticles will be entered through the inlets. When the particles moving through the sensing zone, the resistance will be change in the sensing volume and the setup can sense them.