Next-Generation Diagnostics For Respiratory and Blood-Borne Pathogens

Lim, Jongwon

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https://hdl.handle.net/2142/127357 Copy

Description

Title

Next-Generation Diagnostics For Respiratory and Blood-Borne Pathogens

Author(s)

Lim, Jongwon

Issue Date

2024-11-22

Director of Research (if dissertation) or Advisor (if thesis)

Bashir, Rashid

Doctoral Committee Chair(s)

Bashir, Rashid

Committee Member(s)

• Kong, Hyunjoon
• Cunningham, Brian T
• Smith, Andrew M

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Infectious disease diagnostics, Point-of-care diagnostics, bloodstream infection diagnostics

Abstract

Infectious diseases pose a persistent global threat, with the risk of future pandemics heightened by factors such as climate change, deforestation, and increased global travel. Projections indicate a 40% likelihood of another pandemic caused by respiratory viruses by 2050, with the potential impact comparable to the COVID-19 pandemic, which claimed over 7 million lives worldwide. Compounding this challenge is the rise of antimicrobial-resistant (AMR) bacteria, which is projected to cause 10 million deaths annually by 2050. Together, these threats emphasize the urgent need for transformative diagnostic tools that can rapidly and accurately identify infectious agents in both respiratory and bloodstream infections, particularly in resource-limited settings. Traditional diagnostic approaches, such as blood culture for bloodstream infections or PCR-based methods for respiratory viruses, are often slow, expensive, and dependent on centralized laboratory infrastructure. The COVID-19 pandemic highlighted these limitations, as diagnostic delays and complex sample preparation processes significantly hindered efforts to manage and contain the spread of disease. Moreover, bloodstream infections like sepsis require immediate diagnosis, as delays in treatment can increase mortality rates by 7.6% per hour after septic shock onset. Current methods are inadequate for timely and widespread diagnosis, particularly in low- and middle-income regions, contributing to the rise of drug-resistant pathogens. This research addresses the pressing need for accessible, rapid, and cost-effective diagnostic solutions for respiratory and blood-borne infections. Two critical areas of focus include respiratory viruses, such as SARS-CoV-2, and bloodstream infections like sepsis. To tackle respiratory virus outbreaks, a novel diagnostic platform was developed, which employs a 3D-printed disposable cartridge and a smartphone-based reader. This system allows individuals to test for infections at home using saliva samples, eliminating the need for complex laboratory infrastructure. Testing time was reduced from one day to just one hour, enabling the simultaneous detection of both SARS-CoV-2 and its variants. The platform was further extended to detect multiple respiratory viruses, including Influenza A, Influenza B, and RSV, through a single swab, making it a valuable tool for use in resource-limited settings. In parallel, the second focus of this research aimed at developing a blood-drying method to address the challenges of diagnosing bloodstream infections. By utilizing a novel drying-based coagulation process, the sensitivity of pathogen detection was enhanced, achieving a limit of detection of 1 CFU/mL for pathogens such as E. coli, MRSA, and MSSA. This method, validated with 63 clinical samples, provided 100% sensitivity and specificity, while reducing diagnostic time from over 20 hours to under 2.5 hours. The ability to rapidly identify pathogens allows for more targeted antibiotic treatments, minimizing the misuse of broad-spectrum antibiotics, which is crucial in combating the rise of antimicrobial resistance. Additional studies explored the underlying mechanisms of impurity inactivation, providing a material-based understanding of the dried blood matrix, which further advanced the potential of this approach. By integrating molecular biology, materials science, and micro/nano-engineering, this thesis presents next-generation diagnostic platforms designed to address the key limitations of traditional methods. These innovations decentralize diagnostics, making them faster, more accessible, and cost-effective for a wide range of applications, from detecting respiratory viruses to diagnosing sepsis in resource-limited settings. The work presented contributes to global efforts to improve healthcare outcomes and prepare for future pandemics and antimicrobial resistance crises, aiming to build a future where life-saving diagnostics are available to all.

Graduation Semester

2024-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/127357

Copyright and License Information

Copyright 2024 Jongwon Lim

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