PhD Oral Exam - Seyed Hamid Safiabadi Tali, Chemical and Materials Engineering

When studying for a doctoral degree (PhD), candidates submit a thesis that provides a critical review of the current state of knowledge of the thesis subject as well as the student’s own contributions to the subject. The distinguishing criterion of doctoral graduate research is a significant and original contribution to knowledge.

Once accepted, the candidate presents the thesis orally. This oral exam is open to the public.

Abstract

Low-cost, portable, and easy-to-use analytical devices are crucial for applications ranging from healthcare and environmental monitoring to biotechnology and forensics. Unsafe food, water, and delayed disease detection cause millions of deaths annually, while the COVID-19 pandemic, with severe socio-economic impacts, underscored the urgent need for rapid, reliable diagnostics. To meet these needs, microfluidic paper-based analytical devices (µPADs) and tablet-based assays are promising platforms to develop affordable, portable, and robust detection tools, particularly for resource-limited settings. Yet improvements in µPAD fabrication are needed to enhance accessibility, while challenges remain in colorimetric and electrochemical sensing with respect to precision and sensitivity. For tablet-based assays, further progress is required to achieve efficient mixing in viscous media and integration of bioreagents into auto-mixing tablets for biosensing applications.

This thesis was initiated during the pandemic laboratory shutdown with a comprehensive review of COVID-19 diagnostic methods, which was later published in Clinical Microbiology Reviews and received considerable attention from the research community. The review surveys molecular assays for viral RNA, antigen tests, and serological approaches, providing insights into pandemic preparedness and highlighting gaps in diagnostic technologies. Building on these insights, the main body of the thesis is organized into four interconnected main chapters, all of which corresponding to a key manuscript, focusing on µPADs and tablet-based assays.

First, a review examines µPADs and tablet-based assays focusing on their history, fabrication methods, and detection strategies. Importantly, this work presents the first dedicated literature review of tablet-based assays, consolidating information previously scattered across the literature.

Next, a simplified fabrication method combining Parafilm® heating and CO2 laser cutting was developed, enabling high-resolution µPADs. Novel multi-inlet and segmented detection zones reduced color gradients by more than half, improving precision in colorimetric glucose detection in urine.

Following up, for electrochemical sensing, a do-it-yourself screen-printing method was established using portable equipment costing under 50 USD. Combined with laser-cut vinyl masks, this approach enabled rapid, on-demand electrode fabrication with high resolution. A simple water treatment enhanced signal intensity by over 75-fold, which was nearly doubled again by sandwiching electrodes between two paper layers. These devices were validated for glucose detection in cell culture media, relevant to biotechnology and biopharmaceutical applications.

Finally, tablet-based assays with rapid auto-mixing capability were developed, achieving more than a 100-fold increase in mixing speed and successful operation in viscous media up to 1700 mPa·s. A proof-of-concept was demonstrated for nitrite detection in human saliva, a challenging medium due to its variable viscosity. In addition, a simple mist-sprayer method for reagent encapsulation in trehalose was developed, enabling incorporation of bioreagents into tablets without costly equipment. Using this approach, the first tablet-based biosensor with rapid auto-mixing capability was realized and validated for glucose detection in real human urine.

Overall, the strategies developed herein simplify fabrication, improve performance, and expand the applicability of µPADs and tablet-based assays. By lowering technical and economic barriers, this work hastens research in these areas and advances the translation of these platforms from laboratories toward widespread, real-world use in healthcare, environmental safety, and beyond.