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Title: Probing multivalent particle-surface interactions using a quartz crystal resonator
Author: Da-Silva-Granja, Carlos António
ISNI:       0000 0004 7970 7884
Awarding Body: Loughborough University
Current Institution: Loughborough University
Date of Award: 2019
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The rise in market-approved cellular therapies demands for advancements in process analytical technology (PAT) capable of fulfilling the requirements of this new industry. Unlike conventional biopharmaceuticals, cell-based therapies (CBT) are complex 'live' products, with a high degree of inherent biological variability. This exacerbates the need for in-process monitoring and control of critical product attributes, in order to guarantee safety, efficacious and continuous supply of this CBT. There are therefore mutual industrial and regulatory motivations for high throughput, non-invasive and non-destructive sensors, amenable to integration in an enclosed automated cell culture system. While a plethora of analytical methods is available for direct characterization of cellular parameters, only a few satisfy the requirements for online quality monitoring of industrial-scale bioprocesses. In the last twenty years, quartz crystal resonators (QCR) have demonstrated a high degree of versatility and applicability across different biomedical applications, capable of acting as both gravimetric and force balances. The strain induced by micron-sized particles attached onto the oscillating quartz causes significant deviations inthe magnitude of any odd Fourier harmonic responses, as a function of the oscillation frequency and amplitude. This transduction principle, named Anharmonic Acoustic Detection Technique (ADT), could potentially complement traditional quartz resonators in the study of cell-surface interactions. The initial part of the experimental work covered in this thesis investigates the interactions between model micron-sized particle with surface-immobilized proteins and the QCR. In a coupled oscillator system, the relative amount/density of molecular complexes formed between the particle and the resonator modifies the nonlinear acoustic response measured by the third Fourier harmonic of the current. A second part extends the investigation towards characterization of membrane antigen expression of cord-blood derived CD34⁺ erythroprogenitors, differentiated down the erythroid lineage. The final contribution of this work demonstrates the feasibility of implementing QCR sensors as online quality monitoring tools for surface marker profiling and characterization of cell mechanical properties, features also appropriate for applications in point-of-care clinical diagnostics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Mechanical Engineering not elsewhere classified ; sensors ; nonlinear acoustics ; Cell Therapy Products ; Regenerative medicine ; kinetics assay