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Acoustic Biomolecules for Diagnostic Ultrasound Imaging


Ling, Bill (2023) Acoustic Biomolecules for Diagnostic Ultrasound Imaging. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/va8g-tb47.


Nanotechnology has enabled significant breakthroughs in the early detection and treatment of disease, but many of these advances rely on expensive and less-accessible imaging modalities. Ultrasound, on the other hand, is a noninvasive imaging modality that stands out for its universal availability, cost-effectiveness, and safety. However, harnessing the benefits of nanomaterials for ultrasound has been challenging due to the size and stability constraints of typical ultrasound contrast agents. Recently, an innovative solution has emerged in the form of gas vesicles (GVs), a class of air-filled protein nanostructures found in certain aquatic microbes. These promising next-generation ultrasound contrast agents offer a crucial bridge between nanotechnology and ultrasonography.

In this thesis, we investigate the in vivo behavior of GVs, explore their potential applications as nanodiagnostic agents, and consider key factors for their future clinical deployment. In Chapter 2, we examine the interactions of GVs with blood components, focusing on imaging performance and immunogenicity. In Chapter 3, we show that intravenously injected GVs are cleared by liver-resident macrophages and subsequently undergo lysosomal degradation. We leverage this finding to develop an ultrasound-based method for visualizing cellular degradative processes and demonstrate its potential as a liver disease diagnostic. In Chapter 4, we introduce bicone GVs, the smallest known ultrasound contrast agent. We show that these sub-80 nm particles can penetrate tumors, deliver potent ultrasound-induced mechanical effects, and are readily engineered for molecular targeting, extended circulation time, and payload conjugation.

Together, these findings highlight the tremendous potential of GVs as injectable nanomaterials for ultrasound imaging, laying the foundation for future studies to further refine the design and application of these agents.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:gas vesicles, ultrasound imaging, nanomedicine, protein corona, liver disease
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemical Engineering
Awards:Constantin G. Economou Memorial Prize, 2017.
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Shapiro, Mikhail G.
Thesis Committee:
  • Ismagilov, Rustem F. (chair)
  • Davis, Mark E.
  • Chan, Warren C. W.
  • Shapiro, Mikhail G.
Defense Date:26 May 2023
Record Number:CaltechTHESIS:05312023-220301021
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 3
Ling, Bill0000-0002-1276-7204
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15248
Deposited By: Bill Ling
Deposited On:01 Jun 2023 17:00
Last Modified:16 Jun 2023 17:50

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