PD Dr. Sukhdeep Singh
Head of the Research Group
+49 3677 69 3685
Anschrift:
Technische Universität Ilmenau
Fakultät für Mathematik und Naturwissenschaften
PF 10 05 65
98684 Ilmenau
Besuchsadresse:
Heliosbau, Raum 2111
BioLithoMorphie means the assembly of biological material using lithographic methods for the construction of three-dimensional biological structures or morphologies. In doing so, it aims to transfer fabrication principles of micro- and nanotechnology for the construction of biological, three-dimensional (3D) tissues and their investigation for applications in the "life sciences".
BioLithoMorphie builds on the expertise of the centers of innovation competence MacroNano® and B CUBE to generate a unique selling point in the design of true 3D structures in the "Life Sciences". The aim is to significantly improve in vitro cell culture with the exploitation of these results in the "Life Sciences", i.e. the disciplines at the interface between the fields of biotechnology and medicine, in particular pharmaceutical drug research or tissue engineering. This can be achieved if the correct micro- and macroscopic architecture of a complex cell structure can be reproduced.
Project Manager
Prof. Dr. rer. nat. habil. Andreas Schober Head of Department Nanobiosystems Technology TU Ilmenau
Phone: +49 (0) 3677 69 3387 andreas.schober@tu-ilmenau.de
Dr. Yixin Zhang Junior Research Group Leader B CUBE Dresden
Tel: +49 (0) 351 4634 3040 yixin.zhang@bcube-dresden.de
Assembly of three-dimensional tissue structures
BioLithoMorphie is defined as a method for assembling biological material using the manufacturing processes of micro- and nanotechnology (e.g. UV lithography).
Modern manufacturing processes of microsystems technology as well as new findings in the fields of life sciences and biomaterials, such as 3D cultivation of cells, offer new possibilities in the design of biological systems. To this end, it is necessary to transfer the processes of micro- and nanotechnology to biology so that three-dimensional tissues can be produced.
The aim of the subproject is to develop technologies for structuring, masking and modifying surfaces for complex tissue structures. This makes it possible to create three-dimensional tissue structures based on thin, modified polymer films.
Sensor technologies based on nanostructures
The aim of the project is to develop a highly sensitive sensor using surface-enhanced Raman scattering (SERS) to detect photoswitchable biomolecules.
These highly sensitive SERS sensors are based on clearly aligned gold and silver nanoparticle arrays fabricated on a substrate with ultra-thin aluminum oxide membranes (UTAM) for nanostructuring. In cooperation with the departments of nanobiosystems engineering and electronics engineering, the SERS substrate was integrated into a microbioreactor. This microbioreactor with SERS substrate is used to detect photoswitchable biomolecules (BCUBE Dresden, Dr. Yixin Zhang's group), furthermore in situ studies and cis-trans transformations of photoswitchable biomolecules can be performed under illumination. Furthermore, these anodized alumina (AAO) template-based three-dimensional nanostructures of the integrated SERS and electrochemical sensors are developed to detect biomolecules.
Carrier substrates for biological morphologies
The aim of this subproject is the design and fabrication of LTCC-based carrier substrates on which three-dimensional bilological morphologies can be cultivated.
In collaboration with the FG 3D Nanostructuring, substrates with nanoscale gold particles are developed. These special carrier substrates are suitable for the SERS technology and enable the detection of enriched cell cultures. In the future, cell cultures produced by lithography can be measured and characterized by sensors.
In addition to the SERS-compatible substrates, carrier systems using DNA hydrogels as a sensory layer are being developed together with BCUBE Dresden. The functionality of the DNA hydrogels is based on their resistance change upon contact with protein solutions.
Light responsive cell adhesive micro-fluidic systems
By using a new array technology, a large number of peptides derived from ECM proteins (e.g. fibronectin and laminin) could be tested. These peptides were evaluated for their adhesion to neural progenitor cells (NPC) and human umbilical vein endothelial cells (HUVEC). From these studies, a series of potent and cell type-specific sequences were discovered by high-content screening, which will be used to develop photoswitchable cell-adhesive microfluidic systems. The expansion of this screening technology also offers the possibility of developing a wide range of other applications, from the design of new biologically active agents to applications for cell-based regenerative medicine.
To develop photoswitchable cell-adhesive microfluidic systems, we have expanded our concept of "borrowing protein" to the "borrowing surface" approach. This allows biological functions to be controlled by light; matrix surfaces are larger than protein molecules and thus can enhance the photoswitchable effect. To analyze the photoswitchability, the association and dissociation rates between the protein and the immobilized ligand are measured. Moreover, by varying the light wavelength, the extent of the photoswitchability effect can be dosed. This approach could also be used to develop a photoswitchable protein affinity chromatograph.
Bottom-up synthesis and site-selective modification of hydrogels
By using a novel photochemical reaction - a two-photon [2 + 2] cycloaddition of maleimide groups, we generate hydrogels on activated surfaces in a bottom-up process. The two-photon process allows sub - micron structural precision of hydrogel fibers and thus precise control of stiffness and structure. We further developed a method to modify these hydrogels with an identical photochemistry using organic molecules. In particular, we are developing this system into a two- or even multi-step protocol for the incorporation of biomolecules into hydrogels with submicrometer precision. Within this subproject we develop a platform for site-selective modified hydrogels, including gradients of biomolecules in arbitrary structures.
