Design, development, and validation of portable sensors and systems for label-free probing of bacterial phenotypes in real-time

Restricted (Penn State Only)
- Author:
- Zhou, Keren
- Graduate Program:
- Electrical Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 27, 2023
- Committee Members:
- Madhavan Swaminathan, Program Head/Chair
Zhiwen Liu, Major Field Member
Pak Kin Wong, Outside Unit & Field Member
Seyedehaida Ebrahimi, Chair & Dissertation Advisor
Weihua Guan, Major Field Member - Keywords:
- Biosensor
Electrochemical
Optical
Point-of-care
Bacteria
Phenazines
Biofilm - Abstract:
- Universal healthcare concerns have become a grave and pervasive menace to the world. A concerning trend is emerging – an increasing number of infections, such as pneumonia, tuberculosis, and salmonellosis, are growing resistant to treatment. The potency of antibiotics, once relied upon, is diminishing, posing formidable hurdles in combating these illnesses. Consequently, the repercussions are profound, including extended hospital stays, escalated medical expenditures, and heightened mortality rates. Rapid diagnosis systems and point-of-care (PoC) analysis are in high demand. To fight these challenges, developing multiple-function bacterial sensors and systems helps fill the gap between the significant population increase and limited medical resources. Toward this goal, this dissertation undertakes an interdisciplinary exploration that includes the development of biosensors to study bacterial phenotypes related to their antibacterial response and brain-gut microbiome interaction associated with Parkinson's disease (PD). Chapters 2 and 3 introduce a flexible electrochemical sensor based on laser-induced graphene (LIG) material to study the phenazine molecules secreted by the \textit{Pseudomonas aeruginosa} biofilms and the biofilm response to antibiotics. A series of fabrication methods and optimization strategies are investigated to improve their sensor capabilities. In Chapter 4, the LIG electrode is used to study the \( \alpha\)-synuclein aggregation (because of the protein misfold and plays a central role in PD development) mechanisms and identify potential molecules that inhibit the oxidation of dopamine. In Chapter 5, an optical system powered by machine learning using dynamic laser speckle imaging speckle is developed to study bacterial susceptibility to antibiotics. In Chapter 6, we develop a portable system for antibiotic susceptibility testing based on dynamic laser speckle imaging. Finally, Chapter 7 presents two simple methods for bacterial identification compatible with dynamic laser speckle imaging. Bacterial identification is the first process before antibiotic susceptibility testing in clinical practice. The methods include surface-enhanced Raman spectroscopy and immunomagnetic separation. Through these investigations, we strive to contribute not only to the understanding of sensing materials/systems but also to the practical translation of this knowledge into cutting-edge tools for early detection, monitoring, and addressing diverse health challenges posed by small molecules and microorganisms. In summary, this work shows the remarkable potential inherent in the electrochemical biosensor based on LIG for probing bacterial phenotypes (in both planktonic and biofilm phases) as well as indirect study of their impact on a fundamental question related to the brain-gut microbiome axis. The optical system also shows good potential for antibiotic screening. As we look ahead, the new generation of biosensors enables rapid wellness screening and real-time study of microbial phenotypes in response to therapeutics. The fusion of cutting-edge materials science and innovative device engineering propels us toward a healthier and better world.