Label-free and Multi-parametric Monitoring of Cell-based Assays with Substrate-embedded Sensors

1. Front Matter

   Pages i-xxvi

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2. Introduction

   • Maximilian Oberleitner

   Pages 1-30

3. Objectives

   • Maximilian Oberleitner

   Pages 31-34

4. Methods and Instrumentation

   • Maximilian Oberleitner

   Pages 35-114

5. MQCM: Multiple Cytomechanic Sensing

   • Maximilian Oberleitner

   Pages 115-150

6. QCM-ECIS: Combined Viscoelastic and Dielectric Sensing of Cells

   • Maximilian Oberleitner

   Pages 151-293

7. QCM-OCS: Optochemical Sensing of Temperature and pO₂ in the Cell Surface Junction

   • Maximilian Oberleitner

   Pages 295-343

8. Summary

   • Maximilian Oberleitner

   Pages 345-348

9. Back Matter

   Pages 349-370

   PDF

This thesis describes novel substrate embedded physical sensors that can be used to monitor different types of cell-based assays non-invasively and label-free. The sensors described provide integrative information of the cells under study with an adaptable time resolution (ranging from milliseconds to days). This information about the dynamic cell response to chemical, physical or biological stimuli defines a new paradigm in fundamental biomedical research.


The author, Maximilian Oberleitner, describes approaches in which the cells are directly grown on different sensor surfaces (gold-film electrodes, shear wave resonators or dye-doped polymer films). This approach, with the reacting cells in particularly close proximity and contact with the sensor surface, is key to a remarkable sensitivity, opening the way for a variety of new applications. This thesis not only introduces the fundamentals of each approach, but it also describes in great detail the design
principles and elucidates the boundary conditions of the new sensors.

• Cell-based assays
• Label-free high-content sensing
• Quartz crystal microbalance
• Impedance spectroscopy
• Electric cell-substrate impedance sensing
• Cytomechanic sensing
• Confocal laser scanning microscopy
• Optical temperature and oxygen imaging
• Dynamic cell response
• Biological recognition unit
• Mulitparametric whole-cell biosensing
• Fluorescence lifetime imaging
• Cell culture

• Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Regensburg, Germany

  Maximilian Oberleitner

Maximilian Oberleitner was born in 1983 in Bavaria, Germany and graduated from the University of Regensburg with a Diploma in Chemistry in 2008. Based on this doctoral thesis “Label-free and Multi-parametric Monitoring of Cell-based Assays with Substrate-embedded Sensors” he obtained his PhD in Analytical Chemistry in 2016 in the Institute of Analytical Chemistry, Chemo- and Biosensors at the University of Regensburg under the supervision of Prof. Dr. Joachim Wegener. His research work was focused on the development and improvement of substrate-integrated sensors for the analysis of living cells. These sensors enable the monitoring of cell-substrate interactions and the real-time analysis of assays with adherently grown cells in a non-invasive, label-free and – by combinations of the different types of sensors – even in a multi-parametric manner. Since 2015 he works at a global healthcare company in Austria. As project leader in the quality unit he is responsible for stability studiesand quality evaluations of antibiotics.

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