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Micro/Nanomechanical Sensing for Monitoring Biological Processes

  • Author / Creator
    Jiang, Keren
  • Developing miniature instrumentation for biosensing has attracted an extensive interest due to the demand for selective and sensitive detection of multiple targets at extremely low concentrations with exceedingly small sample volumes. Micro/nano mechanical sensors, such as microcantilevers (MCL), are highly sensitive to mechanical interactions such as force, stress and mass change. Mechanical forces originated from physical and chemical interactions are fundamental in biological process from cellular to molecular scale. MCL sensors with comparable size with cells and biomacromolecules, are sensitive, rapid and reliable transducer platforms for biosensing applications. However, the challenge in developing biosensors lies the specificity and reproducibility. Thus, we focus on optimizing the interfaces of the micro/nanomechanical sensors and exploring new detection methodologies, aiming to reduce non-specific surface binding, improve intrinsic sensor performance and monitor biological process in real-time. By monitoring the micro/nanomechanical property variations using microelectromechanical (MEMs) devices, the thermodynamic and nanomechanical properties of biological processes can be determined. In this thesis, we have developed MCL-based biosensors for various applications including whole cell recognition, protein folding detection, neurotransmitter monitoring and DNA melting measurement. With optimized sensing layers, the MCL-based sensors are capable to distinguish targets with varied dimensions from micrometers to sub-nanometers. Surface stress induced via cell binding, conformational change, and molecular displacement are observed and quantified. With a microfluidic cantilever, the mechanical property of biofluid can be monitored with confined sample volume. Other sensor platforms such as electrical impedance spectroscopy (EIS) and surface plasmon resonance (SPR) are also used for sensing layer optimization and validation. We reviewed and compared MEMs systems which allow measurement of stress/force, mass change/displacement for fluidic samples. We have developed pathogen sensors with a limit of detection (LOD) of 1 cell per µL with high selectivity based on antimicrobial peptides (AMPs) functionalized micromechanical devices. The protonation/deprotonation induced protein conformational change with different pH condition is also analyzed using MCL sensor. A conjugated polymer system is designed for dopamine detection with LOD down to the picomolar range and this system is capable to recognized dopamine from coexisting molecules and structural analogs. We also employed a microfluidic cantilever for measuring the melting temperature of DNA samples and the viscosity change with the melting process. This study provides a novel approach for monitoring micromechanical properties change of biological interactions in real-time with confined sample volume. By monitoring the mechanical property change, the thermodynamic and micromechanical variation of the DNA melting process has been analyzed. Mechanical interactions as one of the fundamental physical properties of biology can be quantified with MCL sensor platforms. Interfacial optimization and novel sensor design such as hollow channel microfluidic cantilevers can improve the selectivity and sensitivity of the sensors and providing further understanding of the micromechanical properties involved in biological processes. Future work will be continued on continued understanding of analyte-sensor interactions; improving the selectivity of the sensor in complexed samples; increasing the sensor stability under harsh sensing environment and minimizing the sensor volume.

  • Subjects / Keywords
  • Graduation date
    Spring 2018
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3HQ3SD4Q
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
  • Specialization
    • Chemical Engineering
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Chung, Hyun-Joong (Chemical and Materials Engineering)
    • Waghmare, Prashant (Mechanical Engineering)
    • Prasad, Vinay (Chemical and Materials Engineering)
    • Oh, Kwang W (Electrical Engineering, University at Buffalo, The State University of New York)