Implementation of sensors and actuators for the characterization of the interaction of bone-cells with artificial surfaces

The Aim of this project is to establish a system to characterize the influence of mechanical stimulation to bone like cells. The stimulation of bone should increase the healing after bone fractures and should decrease bone loss in higher ages. In this project, the important physiological parameters like acidification (pH) and oxygen consumption (O₂) as well as adhesion should be monitored in the stimulated systems to clarify the influence of the stimulation on pH and oxygen conditions in the system. The development of the CMMS (Cell Monitoring and Manipulation System) makes it necessary to investigate the influence of the used materials of CMMS.

In essence, this project includes the following main stages

• Characterization of a bone like cell culture line as test system
• Development of a culture system for bone like cells with ability for mechanical stimulation and perfusion
• Development or modification of sensors for cell characterization
• Development of a stimulation approach
• Comparison of cell growth depending on the stimulation and surface in the system

The tests for the cell compatibility of the CMMS materials showed that the two established cells lines (MG63 and MC3T3-E1) adhere and proliferate on al materials without further coating of the chip surface. Furthermore, I could show that the increase of the pH is advantageous for both cell lines.

For the chip development, a new approach for thin-layer glass chips was introduced using an ultra-short pulse laser system.

Peer-reviewed journal papers:

• BUEHLER, S. M., STUBBE, M., BONK, S. M., NISSEN, M., TITIPORNUN, K., KLINKENBERG, E.-D., BAUMANN, W. and GIMSA, J., 2016. Cell Monitoring and Manipulation Systems (CMMSs) based on Glass Cell-Culture-Chips (GC3s). Micromachines, 7 (7), pp. 106. DOI: 10.3390/mi7070106.
• BONK, S. M., STUBBE, M., BÜHLER, S., TAUTORAT, C., LITWINSKI, C., BAUMANN W., KLINKENBERG, E.-D.and GIMSA  J., 2015. Design and characterization of pH, oxygen and adhesion sensors as well as electro-thermal micro-pumps (ETµPs) for glass chips in sensorized cell-culture systems. Biosensors, 2015, 5, pp. 513-536. DOI:  10.3390/bios5030513.
• BONK, S.M., OLDORF, P., PETERS, R., BAUMANN, W. and  GIMSA, J. 2015. Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses. Micromachines , 6, pp. 364-374. DOI: 10.3390/mi6030364.
• BONK, S.M., and LISDAT, F., 2009. Layer-by-layer assembly of electro-active gold nanoparticle/cytochromeC multilayers. Biosensors and Bioelectronics, 25, pp. 739–744. DOI: 10.1016/j.bios.2009.08.017.

Reviewed paper important congress

• BONK, S.M., OLDORF, P.,  PETER, R., BAUMANN, W.  and GIMSA, J., 2014,  Fast prototyping of multisensory cell culture chips using ultra-short pulse-laser ablation and pcb micromilling. 2nd International Conference on MikroFluidic Handling Systems (MHFS 2014), Freiburg. pp. 181-184.
• OLDENDORF, P., PETERS, R., BONK, S.M. und GIMSA, J. Mikrobearbeitung von glasfaserverstärkten, flexiblen und nanobeschichteten Leiterplatten mittels Ultrakurzpulslaser. 7. DVS/GMM-Tagung Elektronische Baugruppen und Leiterplatten, Fellbach, Feb. 2014, Galvanotechnik Eugen g. Leutze Verlag
• OLDENDORF, P. PETERS, R., BONK, S.M. und GIMSA, J. Hochpräzise Mikrostrukturierung von Nanoschichten mittels ultrakurzer Laserpulse. 9. Thüringer Grenz- und Oberflächentage, Zeulenroda, 09.2013.
• BONK, S.M., OLDENDORF, P., WEIHE, T., STUBBE, M., PETERS, R. und GIMSA, J. 2013. Rapid-Prototyping von Dünnschichtsensoren für Zellkulturchips durch direkte Strukturierung mit einem Ultra-Kurzpulslaser, MST 2013, 14-16.10.2013 Aachen, pp. 830-833.
• WEIHE, T., BONK, S., and GIMSA, J., 2010. Single-Cell Force Spectroscopy for the determination of initial adhesion of cells to different surfaces", Biomedical Engineering. Volume 55, Issue s1, ISSN (Online) 1862-278X, ISSN (Print) 0013-5585, DOI: 10.1515/BMT.2010.545.

Patente

• AZ: DE 10 2014 207 249.2, BONK, S. Planar aufgebaute Peristaltikpumpe für flexible Mikrofluidiksysteme. (Patent angemeldet)
• AZ: DE 10 2014 207 238.7, BONK, S. Planar aufgebaute motorgesteuerte Ventile für flexible Mikrofluidiksysteme. (Patent angemeldet)
• AZ: DE 10 2015 220 651.3, GALOW, A., BONK, S., WYSOTZKI, P., BAUMANN, W., Medizinisches Implantat und Verfahren zu Osteoblastenkultivierung. (Patent angemeldet)

Buchbeiträge

WALTHER, S., BONK, S., STUBBE, M. BAUMANN, W., GIMSA, J., 2014. Mikrofluidik, innere Sensorik und Strukturentwurf für ein 3D-Zellkultursystem. In Knöcherne Geweberegeneration Zellphysiologie im Dreidimensionalen. Neumann, H.-G., Klinkenberg, E.-D., Eds., Shaker: Aachen, 2014, pp. 73–111.

• Prof. Jan Gimsa
• Dr. Werner Baumann