Biology subjects

Smith, C. A. B.

Publications and source records attributed to Smith, C. A. B..

5 recordsLinked to original sources

bioRxiv2025

Thermally controlled state switches for macrophage immunotherapy

Advances in cellular immunotherapy promise new treatments for conditions such as cancer, autoimmune disease, and heart disease. While engineered cells have the ability to recognize clinically relevant signals, traffic to disease sites and interface with the host immune system, their activity must be tightly controlled to minimize undesirable effects in healthy tissues. One approach to obtaining specificity is to activate the cells spatially using externally applied energy, such as ultrasound-delivered heating. To facilitate such control, we designed and characterized a genetic circuit that enables stable transcriptional activation of macrophages after a brief thermal stimulus, resulting in the expression of reporters or secretion of the cytokine IL-12. We demonstrate that in vivo activation of a mouse macrophage cell line containing this bioswitch results in spatially localized gene expression for at least 14 days after ultrasound heating. This thermal bioswitch provides a precise control element for cell-therapeutic agents.

bioengineering↗

bioRxiv2024

Characterisation of Gas Vesicles as Cavitation Nuclei for Ultrasound Therapy using Passive Acoustic Mapping

Genetically encodable gas filled particles known as gas vesicles (GVs) have shown promise as a biomolecular contrast agent for ultrasound imaging and have the potential to be used as cavitation nuclei for ultrasound therapy. In this study, we used passive acoustic mapping techniques to characterize GV-seeded cavitation, utilizing 0.5 and 1.6 MHz ultrasound over peak rarefactional pressures ranging from 100 to 2200 kPa. We found that GVs produce cavitation for the duration of the first applied pulse, up to at least 5000 cycles, but that bubble activity diminishes rapidly over subsequent pulses. At 0.5 MHz the frequency content of cavitation emissions was predominantly broadband in nature, whilst at 1.6 MHz narrowband content at harmonics of the main excitation frequency dominated. Simulations and high-speed camera imaging suggest that the received cavitation emissions come not from individual GVs but instead from the coalescence of GV-released gas into larger bubbles during the applied ultrasound pulse. These results will aid the future development of GVs as cavitation nuclei in ultrasound therapy.

bioengineering↗

bioRxiv2024

Achieving Single Cell Acoustic Localisation with Deactivation Super Resolution

Super-resolution optical microscopy enables optical imaging of cells, molecules and other biological structures beyond the diffraction limit. However, no similar method exists to super-resolve specific cells with ultrasound. Here we introduce Deactivation Super Resolution (DSR), an ultrasound imaging method that uses the acoustic deactivation of genetically encodable contrast agents to super-resolve individual cells with ultrasound as they navigate through structures that cannot be resolved by conventional imaging methods. DSR takes advantage of gas vesicles, which are air-filled sub-micron protein particles that can be expressed in genetically engineered cells to produce ultrasound contrast. Our experimental results show that DSR can distinguish sub-wavelength microstructures that standard B-mode ultrasound images fail to resolve by super- localizing individual mammalian cells. This study provides a proof of concept for the potential of DSR to serve as a super- resolution ultrasound technique for individual cell localization, opening new horizons in the field.

bioengineering↗

bioRxiv2024

Enhanced Ultrasound Image Formation with Computationally Efficient Cross-Angular Delay Multiply and Sum Beamforming

Ultrasound imaging is a valuable clinical tool. It is commonly achieved using the delay and sum beamformer algorithm, which takes the signals received by an array of sensors and generates an image estimating the spatial distribution of the signal sources. This algorithm, while computationally efficient, has limited resolution and suffers from high side lobes. Nonlinear processing has proven to be an effective way to enhance the image quality produced by beamforming in a computationally efficient manner. In this work, we describe a new beamforming algorithm called Cross-Angular Delay Multiply and Sum, which takes advantage of nonlinear compounding to enhance contrast and resolution. This is then implemented with a mathematical reformulation to produce images with tighter point spread functions and enhanced contrast at a low computational cost. We tested this new algorithm over a range of in vitro and in vivo scenarios for both conventional B-Mode and amplitude modulation imaging, and for two types of ultrasound contrast agents, demonstrating its potential for clinical settings.

bioengineering↗

bioRxiv2023

Truly tiny acoustic biomolecules for ultrasound imaging and therapy

Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography has been challenging due to the size and stability constraints of conventional bubble-based agents. Here we describe bicones, truly tiny acoustic contrast agents based on gas vesicles, a unique class of air-filled protein nanostructures naturally produced in buoyant microbes. We show that these sub-80 nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation.

synthetic biology↗