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.

Michael Reichel

Project Coordinator: PD Dr. Sukhdeep Singh


Meta ZIK


Funding: BMBF - Federal Ministry of Education and Research

BioLithoMorphie I (FKZ: 03Z1M511) Project duration: 01.04.2014 - 31.05.2015

BioLithoMorphie II (FKZ: 03Z1M512) Project duration: 01.10.2015 - 28.02.2019


Project title: Assembly of biological material using lithographic methods to construct three-dimensional biological morphology.




Project Manager

Prof. Dr. rer. nat. habil. Andreas Schober Head of Department Nanobiosystems Technology TU Ilmenau

Phone: +49 (0) 3677 69 3387


Dr. Yixin Zhang Junior Research Group Leader B CUBE Dresden

Tel: +49 (0) 351 4634 3040


FG Nanobiosystems Technology

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.

FG 3D Nanostructuring

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.

FG Electronics Technology

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.

Research Group Zhang

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.

Research Group Schlierf

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.


Journal articles

Yan Mi, Liaoyong Wen, Rui Xu, Zhijie Wang, Dawei Cao, Yaoguo Fang, Yong Lei Constructing an AZO/TiO2 Core/Shell Nanocone Array with Uniformly Dispersed Au NPs for Enhancing Photoelectrochemical Water Splitting Advanced Energy Materials, 2015 DOI: 10.1002/aenm.201501496

Zhibing Zhan, Fabian Grote, Zhijie Wang, Rui Xu, Yong Lei Degenerating Plasmonic Modes to Enhance the Performance of Surface Plasmon Resonance for Application in Solar Energy Conversion Advanced Energy Materials, 2015 DOI: 10.1002/aenm.201501654

Kai Zhang, Xiaoyong Deng, Qun Fu, Yun Meng, Huaping Zhao, Wenchong Wang, Minghong Wu, Yong Lei Photolithography Compatible Templated Patterning of Functional Organic Materials in Emulsion Advanced Science, in press.

Qun Fu, Zhibing Zhan, Jinxia Dou, Xianzheng Zheng, Rui Xu, Minghong Wu, Yong Lei Highly Reproducible and Sensitive SERS Substrates with Ag Inter-Nanoparticle Gaps of 5 nm Fabricated by Ultrathin Aluminum Mask Technique ACS Applied Materials & Interfaces, vol. 7, issue 24, p. 13322-13328, 2015 DOI: 10.1021/acsami.5b01524

Liying Liang, Yang Xu, Chengliang Wang, Liaoyong Wen, Yaoguo Fang, Yan Mi, Min Zhou, Huaping Zhao, Yong Lei Large-scale highly ordered Sb nanorod array anodes with high capacity and rate capability for sodium-ion batteries Energy and Environmental Science,issue 8, p. 2954-2962, 2015 DOI: 10.1039/C5EE00878F

Chengliang Wang, Yang Xu, Yaoguo Fang, Min Zhou, Liying Liang, Sukhdeep Singh, Huaping Zhao, Andreas Schober, Yong Lei Extended π-Conjugated System for Fast-Charge and -Discharge Sodium-Ion Batteries Journal of the American Chemical Society, vol. 137, issue 8, p. 3124-3130, 2015 DOI: 10.1021/jacs.5b00336

Fabian Grote, Huaping Zhao, Yong Lei Self-supported carbon coated TiN nanotube arrays: innovative carbon coating leads to an improved cycling capability for supercapacitor applications Journal of Physical Chemistry C, vol. 119, issue 28, p. 16331-16337, 2015 DOI: 10.1039/C4TA05905K

Ahmed Al-Haddad, Zhijie Wang, Rui Xu, Haoyuan Qi, Ranjith Vellacheri, Ute Kaiser, and Yong Lei Dimensional Dependence of Optical Absorption Band Edge of TiO2 Nanotube Arrays beyond Quantum Effect Journal of Physical Chemistry C, vol. 119, issue 28, p. 16331-16337, 2015 DOI: 10.1021/acs.jpcc.5b02665

Wieduwild, R.; Krishnan, S.; Chwalek, K.; Boden, A.; Drechsel, D.; Werner, C.; Zhang, Y.: Non-covalent matrix beads as microcarriers for cell culture Angew. Chem. Int. ed. Engl, vol. 54. issue 13, p. 3962-3966, 2015.

Yan Mi, Liaoyong Wen, Zhijie Wang, Dawei Cao, Yaoguo Fang, Yong Lei Building of anti-restack 3D BiOCl hierarchitecture by ultrathin nanosheets towards enhanced photocatalytic activity Applied Catalysis B: Environmental, vol. 176-177, p. 331-337, 2015 DOI: 10.1016/j.apcatb.2015.04.013

Liying Liang, Yang Xu, Xin Wang, Chengliang Wang, Min Zhou, Qun Fu, Minghong Wu, Yong Lei Intertwined Cu3V2O7(OH)2-2H2O nanowires/carbon fibers composite: A new anode with high rate capability for sodium-ion batteries Journal of Power Sources, vol. 294, p. 193-200, 2015 DOI: 10.1016/j.jpowsour.2015.06.076

Qun Fu, Kin Mun Wong, Yi Zhou, Minghong Wu, Yong Lei Ni/Au hybrid nanoparticle arrays as a highly efficient, cost-effective and stable SERS substrate RSC Advances, issue 5, p. 6172-6180, 2015 DOI: 10.1039/C4RA09312G

Mi, Y.; Wen, L.; Wang, Z., Cao, D.; Zhao, H.; Zhou, Y.; Grote, F.; Lei, Y. Ultra-low mass loading of platinum nanoparticles on bacterial cellulose derived carbon nanofibers for efficient hydrogen evolution Catalysis Today, In Press. DOI: 10.1016/j.cattod.2015.08.019

Singh, S.; Friedel, K.; Himmerlich, Marcel.; Lei, Y.; Schlingloff, G.; Schober, A. Spatiotemporal Photopatterning on Polycabonate Surface through Visible Light Responsive Polymer Bound DASA Compounds American Chemical Society: Macro Letters, issue 4, p. 1273-1277, 2015 DOI: 10.1021/acsmacrolett.5b00653 .

Lin, W.; Reddavide, F. V.; Uzunova, V.; Gür, F. N.; Zhang, Y. Characterization of DNA-Conjugated Compounds Using a Regenerable Chip American Chemical Society: Analytical Chemistry 87, issue 2, p. 864-868, 2015 DOI: 10.1021/ac503960z .

Quintero, A.; Lin, W.; Hermanna, S.; Zhang, Y. Light Induced Inhibition of Protein Phosphatase Calcineurin WILEY: Chinese Journal of Chemistry, vol. 32, issue 10, p.1011-1014, 2014 DOI: 10.1002/cjoc.201400432

Singh, S.; Lei, Y; Schober, A.: Direct extraction of carbonyl from waste polycarbonate with amines under environment friendly conditions: scope of waste polycarbonate as carbonylating agent in organic synthesis Royal Journal of Chemistry: RSC advance, issue 5, p. 3454-3460, 2015 DOI: 10.1039/C4RA14319A

Thompson, M.; Tsurkan, M.; Chwalek, K.; Bornhauser, M.; Schlierf, M.; Werner, C.; Zhang, Y.: Self-assembling hydrogels crosslinked brinely by receptor-ligand interactions: tunability, rationalization of physical properties and 3D cell culture WILEY: Chemistry - A European Journal, vol. 21, issue 8, p. 3178-3182, 2015 DOI: 10.1002/chem.201406366

Tobola, J; Hampl, J.; Gebinoga, M.; Elsarnagawy, T.; Elnakady, Y. A.; Fouad, H.; Almajhadi, F.; Fernekorn, U.; Weise, F.; Singh, S.; Elsarnagawy, D.; Schober, A.: Thermoforming techniques for manufacturing porous scaffolds for application in 3D cell cultivation ELSEVIER: Materials Science and Engineering C, vol. 49, p. 509-516, 2015 DOI: 10.1016/j.msec.2015.01.002

Vellacheri, R.; Al-Haddad, A.; Zhao, H. P.; Wang, W. X.; Wang, C. L.; Lei, Y.: High performance supercapacitor for efficient energy storage under extreme environmental temperatures ELSEVIER: Nano Energy, vol. 8, p. 231-237, 2014 DOI: 10.1016/j.nanoen.2014.06.015

Wang, C. L.; Fang, Y. G.; Wen, L. Y.; Zhou, M.; Xu, Y.; Zhao, H. P.; De Cola, L.; Hu, W.P.; Lei, Y.: Vectorial diffusion for facial solution-processed self-assembly of insoluble semiconductors: a case study on metal phthalocyanines WILEY: Chemistry - A European Journal, vol. 20, p. 10990-10995, 2014 DOI: 10.1002/chem.201403702.

Zhang, H. C.; Zhou, M.; Fu, Q.; Lei, B.; Lin, W.; Guo, H. S.; Wu, M. H.; Lei, Y.: Observation of Defect State in Highly Ordered Titanium Dioxide Nanotube Arrays IOP Publishing: Nanotechnology, vol. 25, 275603, 2014 DOI: 10.1088/0957-4484/25/27/275603.

Zhao, H.P.; Wang, C.L.; Vellacheri, R.; Zhou, M.; Xu, Y.; Fu, Q.; Wu, M.H.; Grote, F.; Lei, Y.: Self-supported Metallic Nanopore Arrays with Highly-Oriented Nanoporous Structure as Ideally Nanostructured Electrode for Supercapacitor Application. WILEY: Advanced Materials , vol. 26, issue 45, p. 7654-7659, 2014 DOI: 10.1002/adma.201402766

Zheng, Y; Wang, W.; Fu, Q.; Wu, M.; Shayan, K.; Wong, K. M.; Singh, S.; Schober, A.; Schaaf, P.; Lei, Y.: Surface-Enhanced Raman Scattering (SERS) Substrate Based on Large-Area Well-Defined Gold Nanoparticle Arrays with High SERS Uniformity and Stability WILEY: ChemPlusChem, vol. 79, issue 11, p. 1622-1630, 2014 DOI: 10.1002/cplu.201402154.


Zhou, M.; Bao, J.; Xu, Y.; Zhang, J.J.; Xie, J. F.; Guan, M. L.; Wang, C. L.; Wen, L. Y.; Lei, Y.; Xie, Y.: Photoelectrodes Based Upon Mo:BiVO4 Inverse Opals for Photoelectrochemical Water Splitting American Chemical Society: ACS Nano, vol. 8, p. 7088-7098, 2014 DOI: 10.1021/nn501996a.

Conference presentations

Sukhdeep Singh, Andreas Schober Harvesting preserved carbonyl from waste polycarbonate: A scope for synthesis of urea derivatives,bisphenol-A recovery and polycarbonate functionalization (Poster Presentation) Proceedings of 15th Tetrahedron Symposium, 2014, London (UK)

Andreas Schober, Michael Gebinoga, Sukhdeep Singh, Uta Fernekorn, Jörg Hampl, Gregor Schlingloff Methods for modeling 3D cellular environments (Invited Keynote lecture) Proceedings of E-MRS 2014 FALL MEETING, 2014, Warsaw (Poland).

Sukhdeep Singh, U. Fernekorn, G. Schlingloff, J. Hampl, F. Weise, J. Borowiec, A. Andreas Schober Biolithomorphy - an approach for designing tissue-like structures for microfluidic systems (Oral Presentation) 8th Workshop of Chemical and Biological Micro Laboratory Technology, Feb. 23-25, 2016, Elgersburg (Germany).

Patrick Mai, Justyna Borowiec, Jörg Hampl, Frank Weise, Sukhdeep Singh, Gregor Schlingloff, Andreas Schober Designs for scaffold based organotypic cell culture systems (Poster Presentation) 8th Workshop of Chemical and Biological Micro Laboratory Technology, Feb. 23-25, 2016, Elgersburg (Germany)


Andreas Schober, Jörg Hampl, Frank Weise, Sukhdeep Singh, Gregor Schlingloff Shaped body for reproducing a structure of a biological tissue and method for its production Patent application DE 10 2014 112 660.2

Book chapters

Uta Fernekorn, Jörg, Hampl, Frank Weise, Sukhdeep Singh, Justyna Tobola, Andreas Schober Development of Microstructuring Technologies of Polycarbonate for Establishing Advanced Cell Cultivation Systems Book Chapter of "Handbook of Polymers for Pharmaceutical Technologies: Processing and Applications" 2015 DOI: 10.1002/9781119041412.ch3