2022 Thayer Investiture

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PhD Thesis Defense: Alison Burklund

Apr

05

Monday
1:00pm - 2:00pm EST

Videoconference

For info on how to attend this videoconference, please email alison.burklund.TH@dartmouth.edu

"Micro-Scale Bacterial Isolation & Detection Platforms for Rapid Disease Diagnosis"

Abstract

The rapid characterization of bloodstream infections is critical to informing targeted and effective antibiotic therapy and improving patient outcomes. That said, time-intensive, culture-based methods are still ubiquitous for pathogen detection due to the low concentration of bacteria in the bloodstream. Following pathogen detection, additional molecular and/or culture-based methods are required to identify and characterize the antibiotic susceptibility of the sepsis-causing pathogen. Integrated micro-scale systems could aid in shortening diagnostic timelines, due their demonstrated efficacy as high-throughput, sensitive, and specific biomarker isolation and detection platforms.

This thesis demonstrates the development of micro-scale systems for bacterial isolation, lysis, and detection in effort to decrease total-analytical-time and increase diagnostic specificity. First, we investigate the use of porous and dual-functional materials for pathogen screening and sample preparation. We demonstrate the use of a novel paper-based analytical device for the colorimetric detection of species-specific volatile biomarkers in the headspace of bacterial culture. We also describe a size-based filtration methodology using actuated polyvinylidene fluoride to separate bacteria from blood. Next, we discuss the development of microfluidic separation approaches, novel lysis methodologies, and species-specific detection modalities. We present a method for on-chip, contact-free bacterial lysis using an AC magnetic field to enable downstream molecular characterization of captured bacteria. As a capstone to this work, we describe an integrated microsystem that couples microfluidic immunomagnetic bacterial localization to nanoplasmonic molecular profiling for the rapid, species-level characterization of bacteria. The continued development of this integrated system aims to enable culture-free and amplification-free, multiplexed pathogen detection from complex biological matrices.

Thesis Committee

  • John X.J. Zhang, PhD (Chair)
  • Margaret E. Ackerman, PhD
  • Isabella W. Martin, MD
  • Stephen Laderman, PhD (Agilent Research Labs)

Contact

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.