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Projekte

Projects – AG Constantinou

Cascade Biocatalysis in Droplet Microfluidics

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.

Droplets

Project period: 09/2022 - 09/2025

Funding organization: DFG

Responsible person: Lanting Xiang

 

Decoding Lyme Disease: From Microtechnology to Biomechanics

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 blacklegged ticks: Borrelia burgdorferi
The blacklegged ticks: Borrelia burgdorferi

Project period: 08/2020 - 10/2023

Funding organization: Volkswagen Stiftung

Project Responsible: Hazal Kutluk

The role of cellular biomechanics in intestinal infection

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.

Microscopic view of intestine-like structures of Caco-2 cells
Microscopic view of intestine-like structures of Caco-2 cells

Project period: 03/2021-02/2023

Funding organization: Volkswagen Stiftung

Project responsible: Victor Krajka

EpiStretch - Deciphering host-pathogen interactions using an organotypic stretching device and biomechanical approaches

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 mechanical stretch and fluidic flow are limited in their applicability for comprehensive biomechanical infection assays including live-cell imaging.

In this project we develop a cell-stretching platform for videomicroscopy of living cells under cyclic stretching, which is applied to infection assays of Listeria Monocytogenes (LM) bacteria. This platform allows for cell stretching in multiple stretch patterns, access from top for infection assays, live-cell microscopy and application of traction force microscopy.

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 digital image correlation techniques to microscopy images of stretched membranes with tracer particles.

Further information can be found in our recently published paper: https://doi.org/10.1002/advs.202408853 

EpiStretch - Deciphering host-pathogen interactions using an organotypic stretching device and biomechanical approaches

Project period: 03/2022 - 05/2025

Funding organization: DFG

Project responsible: David Jaworski

Micro electrical impedance tomography on chip

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.

EIT

Project period: 06/2023 - 

Funding organization: SMART BIOTECS - Land Niedersachsen

Project responsible: Chang Liu

3D-Bioprinted Scaffolds for Tissue Engineering

Over the past several decades, the field of tissue engineering has made remarkable progress in developing functional tissue substitutes for regenerative medicine. However, traditional scaffold-based methods often struggle to replicate the functionality and complexity of native tissues. One significant challenge is creating larger constructs, as nutrient transport within the inner parts of scaffolds can be inadequate, leading to oxygen deficiency and acidification.

3D bioprinting offers compelling prospects for scaffold fabrication as it allows for the precise placement of cells, biochemical factors, and biomaterials through a layer-by-layer process. Unlike conventional methods, 3D bioprinting has the potential to mimic the complex microstructures of biological tissues and allows for accurate control over cell distribution. Despite these advantages, designing scaffolds that closely mimic innate tissue structures like bone or cartilage for clinical use remains an active area of research. Our project aims to advance this field by fabricating a novel scaffold with a stratified structure, designed to enhance nutrient transport and cell perfusion. Utilizing coaxial 3D printing technology, we will create core/shell prints that integrate hollow channels for efficient nutrient and drug delivery. Following fabrication, we will evaluate the scaffold’s function, compatibility with cell lines, and its ability to deliver essential nutrients and drugs. By focusing on both structural integrity and functional performance.

3D-Bioprinted Scaffolds for Tissue Engineering

Project period: 2024-

Funding organization: DAAD

Project responsible: Mehwish Yousaf

Projects – AG Dietzel

Cell Mechanics by Measured Impedance (CM²I)

Project responsible: Osama Alalul

CM²I investigates the mechanical properties of oocytes through impedance flow cytometry in a microfluidic platform. The system features a microchannel with coplanar microelectrodes, where oocytes—suspended in a conductive medium—flow through the sensing region. A high-precision lock-in amplifier and current amplifier measure the differential impedance response at multiple frequencies.

By analyzing the real and imaginary impedance components, the study correlates electrical signatures with cellular mechanics, enabling non-invasive characterization. Hydrogel microspheres with known properties serve as calibration standards, ensuring accurate interpretation of the impedance data. This research advances label-free, high-throughput biophysical analysis for reproductive biology and biomedical applications.

Computational models streamline the design of microfluidic devices

Experimental work mostly expensive, time consuming, and labor-intensive. This computational tool can generate an optimal design for a complex fluidic device such as a mixer. The computational model could make it faster and cheaper to shape fluidic devices for all sorts of applications, such as microfluidic labs-on-a-chip that can diagnose disease from a few drops of blood or artificial hearts that could save the lives of transplant patients. That shape would drive a high-performing device. With this design in hand, we could utilize 3D printing technology to manufacture the fluidic device. We plan to enhance the computational system by utilizing a more complex and reliable fluid simulation model. This could enable the fluid device to be used in more complex flow environments, which would allow it to be used in more complicated application cases. It takes us a little closer to design tools that can both reduce the number of human design cycles needed and generate novel fluid devices shapes that are optimized and more efficient.

Project Period: 05/2020 - 04/2026

Project Responsible: Songtao Cai

Continuous Non-Aqueous Sol-Gel Synthesis of Metal Oxide Nanoparticles in Microfluidic Systems

This project aims to develop a novel microfluidic system for the continuous synthesis and real-time monitoring of metal oxide nanoparticles using a non-aqueous sol-gel method. Traditional batch processes often face scalability, reproducibility, and process control challenges, along with limited real-time monitoring capabilities. Through the utilization of microfluidics, this system will fulfill the entire process from fluid introduction to precursor reaction and particle synthesis. The microfluidic platform will also utilize impedance spectroscopy as an analytical tool for high-resolution monitoring of nanoparticle formation and reaction dynamics. This approach will ensure stable and reproducible synthesis, leading to precise control of particle size, morphology and material characterization. As a proof of concept, the project will focus on the synthesis of two different metal oxides, continuously tracking their formation and evolution over time. This will demonstrate the platform’s efficiency, process control capabilities, and potential for high-throughput material synthesis, offering valuable insights for applications in electronics, catalysis, and advanced materials research.

Continuous Non-Aqueous Sol-Gel Synthesis

Project period: 07/2024 – 07/2027

Funding organization: DFG

Project responsible: Wei Zhao

Flexible exoskeleton with sensor feedback for hand rehabilitation (Joint PhD program TUBS-UTC)

Support for the elderly has been a field of innovation and research that has been booming over the last decade. Often, monitoring systems, mostly based on applications connected to a network, allow the resumption of physical activity or to know the state of awakening of dependent people. These systems are essential to improve people's living conditions, especially their autonomy. Despite this progress, there is still a lot to be done so that the systems can assist people in their daily activities when they are disabled, either by the reduction of their mobility (walking problems) or by the impossibility of doing essential actions (for instance to grasp an object with one’s hand). Exoskeletons may be the solution, but they still remain today too large and heavy.

Within this context, the thesis aims to propose solutions for the rehabilitation of the hand of people with injuries or lack of hand dexterity and give them the possibility of recovering normal grip strength after a training program.

Flexible Exoskeleton Component

Project period: 11/2023 – 11/2026

Funding organization: UFA-DFH PhD track program

Project responsible: Huawei Zheng

FOR 3022 - Ultrasonic Monitoring of Fibre Metal Laminates Using Integrated Sensors

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.

FOR3022
FOR3022

Project period: 01/2023 – 01/2025

Funding organization: DFG

Project responsible:  Jan Niklas Haus

Micro-Replacement Systems: Development of complex microphysiological animal replacement systems for fundamental research in the field of infection and inflammation of the digestive and respiratory tract

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.

Micro-Replacement Systems

Project period: 01/2023 – 12/2025

Funding organization: Land Niedersachsen

Project responsible: Bo Tang

Multifunctional Bondline - Multifunctional bondline with crack stopping function and gradient capable sensors for structural health monitoring as a joining technology for carbon fiber based lightweight structures

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.

Multifunctional Bondline - Multifunctional bondline with crack stopping function and gradient capable sensors for structural health monitoring as a joining technology for carbon fiber based lightweight structures
Multifunctional Bondline - Multifunctional bondline with crack stopping function and gradient capable sensors for structural health monitoring as a joining technology for carbon fiber based lightweight structures

Project period: 09/2023 – 09/2025

Funding organization: DFG

Project responsible: Ann-Kathrin Klein 

NeuroExaminer - a microfluidic device for physiology-based neural circuit analysis

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.

A microfluidic device for physiology-based neural circuit analysis

Project period: 08/2020 – 05/2024

Funding organization: DFG

Project responsible:  Dominika Schrödter

PARS: Programmable Aperture for Resistive Sensing of Nanoparticles

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.

PARS

Project period: 06/2023 – 12/2025

Funding organization: DFG

Project responsible: Mohadeseh Mozafari

Skills4chips

As part of the nationwide flagship project “Skilled workers for microelectronics: skills4chips”, the Federal Ministry of Education and Research (BMBF) is funding the establishment of a national training academy for microelectronics and microsystems technology - the Microtec Academy.

An increased focus on the production of semiconductors “made in Europe” also means an increased demand for qualified specialists for the chip industry. The European Union has set itself the goal of increasing the proportion of semiconductors produced in Europe from 10 to 20 percent by 2030 and specifically promoting regional semiconductor production as part of the European Chip Act. In order to expand these production capacities, a highly qualified workforce is required. This is where the skills4chips project in Germany comes in: With the Microtec Academy, it enables the establishment of a national education platform for microelectronics and microsystems technology. The BMBF is providing a funding volume of 12 million euros over four years for this purpose.

The TU Braunschweig has a fully equipped clean room for research, development and teaching. The teaching staff have many years of experience in the development and practical use of multimedia, interactive teaching modules. These modules will be further developed in the course of the project and made available nationwide for training and further education by the Microtec Academy.

Chip for Health

Project period: 2024-

Funding organization: 

Project responsible: Gabor Homolya

Sucessfully completed: BM=x³ - Innovative improvement of the vocational training for the micro- and nanotechnologies with innovativ concepts to establish an equivalent alternative to academic training

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

Project responsible: Gabor Homolya

Successfully completed: DETECTED - DLS feedback controlled continuous particle production

The new NanoGenSizer has been developed by IMT Braunschweig and Fraunhofer IMM in Mainz to enable researchers to produce a wide range of nanoparticles on a laboratory scale. A 3D microfluidic channel called the Low Aspect Ratio Laminar Mixer (LARLM) promises unique conditions for the controlled and continuous production of nanoparticles with unprecedented synthesis properties, reducing fouling and flow rate dependencies. The system's unique implementation of real-time Dynamic Light Scattering in-line analysis allows rapid determination of optimal and long-term stable process parameters. For process development applications, the system enables users to quickly gain a deep understanding of the process using minimal sample volumes.

Key Facts:

  • 3D microfluidic fabrication technology:  Two-photon polymerization
  • Synthesis technology: Flow focusing (organic phase forms a uniformly thin sheet layer in the channel centre).
  • Particle types: Particles produced by precipitation (e.g., Lipid Nanoparticles).
NanoGenSizer

Project period: 06/2020 - 12/2023

Funding organization: DFG

Project responsible: Ebrahim TaiediNejad

Successfully completed: Embedded Sensors - FRP embedded micro-sensors on multifunctional substrates for curing process control

In the embedded sensors project, a curing monitoring system for CFRP components is to be developed in order to control the curing process even more precisely. This is to be integrated directly within the laminate and provide real-time data during curing in the autoclave as well as material data for health monitoring during subsequent operation in order to detect component failure at an early stage. A sensor package with capacitors (interdigital structures), strain and temperature sensors will be structured on a carrier film, which will chemically bond with the epoxy resin so that the sensor itself causes as little structural weakening as possible. The sensor structures will be produced in three different ways, photolithographically, by selective laser ablation and by the LIFT process, the direct printing of metallic gold pixels.

Embedded Sensors
Embedded Sensors

Project period: 10/2018 – 09/2021

Funding organization: DFG

Project responsible: Korbinian Rager

Successfully completed: FlexMax - Flexible aktive Sensormatrix für medizinische Anwendungen

Goal of the project is to fabricate an ultra-thin, stretchable, flexible bending sensor array that can be attached at the belly of a premature baby. All the bending sensors consist of strain gauges, which are integrated into both sides of a polyimide film. Every two upper und two lower strain gauges  are connected through the polyimide film by using the vertical interconnect accesses (i. e. vias) into a Wheatstone bridge, so they can measure the shape change of the premature infant belly and feed it back by an electrical signal. During breathing the belly of the premature baby becomes periodic larger and smaller which will cause a vibration of the electrical signal. For the baby's health, only the following materials can be used to produce the bending sensor array: gold, titan, Polyimide, PDMS and copper.

Flexible aktive Sensormatrix für medizinische Anwendungen
Flexible aktive Sensormatrix für medizinische Anwendungen

Project period: 04/2018 – 06/2021

Funding organization: BMBF

Project responsible:  Maolei Zhou

Successfully completed: HomeoHirn - Microfluidic perfusion chip to assess maladaptive plasticity in neurodegenerative diseases

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).

 

HomeoHirn

Project period: 04/2021 – 03/2024

Funding organization: Niedersächsischer Vorab (Volkswagen Foundation)

Project responsible: Victor Krajka

Successfully completed: Micro Reactors - Micro reactors for biopharmaceutical applications
Micro Reactors

Project period: 04/2019 – 09/2020

Funding organization: DFG

Project responsible: Sven Meinen

Successfully completed: Paper-Based Biosensor - Calibrated biosensor On-a-Chip for small analytes in Point-of-Care devices an environmental analysis

The use of paper test strips for illness detection and monitoring is gaining importance in the last years, as they offer fast and low cost results that can be obtained not only by medical personal, but also by normal users at home (“Anywhere care”). The objective of this work is to design a self-calibrating platform that enables the detection and quantification of small analytes for on-line blood monitoring, in order to be used in Therapeutic Drug-Monitoring (TDM), but also in fast tests for water quality assurance in swimming pools.

The challenges involving this project are the calibration of the system (issues like age depence results or batch-to-batch variations) and the results evaluation with the camera of a smart-phone. The approaches proposed to solve these problems are strips with more channels for better reproducibility, channels with controlled flow velocity and the implementation of new assays.

Calibrated biosensor On-a-Chip for small analytes in Point-of-Care devices an environmental analysis
Calibrated biosensor On-a-Chip for small analytes in Point-of-Care devices an environmental analysis

Project period: 05/2020 – 08/2022

Funding organization: BMWi (IGF project)

Project responsible:  Esteban Builes

Successfully completed: SmartNIV - Intelligentes, hochelastisches & nichtinvasives Beatmungssystem für Früh- und Neugeborene

Every 10th newborn baby is a premature birth, worldwide. Progress in the care of very immature premature babies has led to a rate of healthy survival of over 90% today, compared to marginal survival rates 40 years ago. One of the key building blocks has been the improvement of ventilation. Studies have shown that ventilation triggered by self-breathing leads to significantly better long-term results than ventilation modes used in the past. In order to further increase the rate of healthy survival, it is therefore necessary to further develop ventilation in such a way that the ventilator is triggered by the child's own breathing using an easy-to-use sensor system.

The goal of smartNIV is the development of an intelligent non-invasive ventilation system for premature infants, which is controlled by a highly elastic multi-sensor patch. This patch is applied to the skin at the transition between chest and abdomen to measure the typical deformations of the thorax caused by breathing and to provide the ventilator with a control signal.

The multi-sensor concept offers the advantage that the failure of even several sensors does not lead to the failure of the entire system. In addition, the flat patch is intended to increase the tolerance against positional inaccuracies to such an extent that simple but reliable application by medical personnel is guaranteed. Furthermore, the patch can be easily resized and is therefore also suitable for very small premature babies. In addition to the novel, highly elastic sensor hardware, the innovation lies in the evaluation software based on artificial intelligence, which will adapt automatically and in real time to the ventilation situation. Conventional systems are hard-coded and therefore very susceptible to interference compared to e.g. unexpected child movements.

All in all, this new medical technology should not only enable triggered respiratory support, but also the recording of the entire respiratory curve, i.e. not only the beginning of inhalation, but also the beginning of exhalation and the intensity of the breathing effort in between. For the first time ever, non-invasive, gentle ventilation would be able to support the breathing effort of a premature infant to the nearest millisecond, which is currently only available for invasive ventilation. It is expected that this will not only relieve the financial burden on the healthcare system, but will also give premature and newborn babies significantly better chances of surviving healthy.

In order to exploit the results, the project consortium aims at a downstream development of the demonstrator into an approved medical device. The supply of the hardware and software as well as the final production and marketing of the entire system should be handled within the consortium.

smartNIV

Project period: 07/2020 – 12/2022

Funding organization: BMBF

Project responsible: Eugen Koch


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