Krista Jackson
BME PhD Defense Presentation
Date: 2026-08-27
Time: 1 PM
Location / Meeting Link: Atwood 360 https://emory.zoom.us/j/94819907035?pwd=gMXFtxCWoKh89VO1eivLiESJMmViRF.1
Committee Members:
Dr. Khalid Salaita, Dr. Yonggang Ke, Dr. Gabriel Kwong, Dr. Hang Lu, Dr. Shuchi Takayama
Title: Redefining the Diagnostic Limits of DNA-Based Rolling Machines: Using Aptamer Switches and Diffusional Analysis to Expand the Target Analyte Scope
Abstract:
Rapid and accurate diagnostics are the key to combatting the spread of infectious diseases through control measures and timely administration of treatment. The current gold standard for detection – PCR – is sensitive but requires expensive reagents, experienced personnel, and complex equipment, restricting access to low resource settings. Point-of-care biosensors provide a rapid and accessible alternative to conventional diagnostics. They usually indicate pathogen detection with optical, electrochemical, or mass-based signals. The lateral flow assay (LFA) is an optical biosensor and a popular choice as a companion diagnostic, rapidly indicating detection through facile readout. However, LFA sensitivity is limited by a reliance on endpoint signals, which can mask transient binding interactions that occur with lower concentrations of the target pathogen. Rolosense and Fuel-Free Rolosense can bypass this limitation through mechanotransduction: a novel paradigm for signal generation by indicating viral detection through changes in the diffusional behaviors of aptamer-functionalized microparticles. In these assays, the DNA-based rolling machines either roll across the chip in the absence of viral targets or stall due to multivalent aptamer-target binding. This strategy allows for sensitive and specific readout in as little as 15 minutes without the need for amplification or expensive imaging equipment. Additionally, the stalling of particles in reaction to aptamer-target binding can be viewed in real time. However, the biosensing capacity of the Rolosense assays has only been indicated for intact virions through aptamer sandwich detection, limiting detection to targets above a certain size threshold that present multivalent binding sites. In this dissertation, we broadened the biosensing scope of the Rolosense systems by incorporating aptamers selected to detect alternate target analytes (i.e. bacteria and proteins). Additionally, we used deep learning-assisted diffusional analysis (i.e. DeepSPT) to more precisely examine how and when the aptamer-target interactions translate into changes in particle motion. We then used these new metrics to investigate how that translation varies when different targets beyond viruses are applied in the assay. Finally, we designed Pro-Rolosense, which bypasses the need for sandwich detection by triggering changes in motor motion through conformational switching of aptamers on the DNA motor. In the absence of its protein target, the aptamer binds to its chip-bound DNA complement, causing motor stalling. If the motor is added to the chip after incubating in a protein solution, the aptamer is bound to its protein target and is unavailable to bind to its DNA complement, allowing motor motion. Overall, this work expands the biosensing potential of DNA-based rolling machines as a novel diagnostic approach towards the remaining challenges of infectious disease detection.
