Harmonic imaging for nonlinear detection of acoustic biomolecules.

Gas vesicles (GVs) based on acoustic reporter genes have emerged as potent contrast agents for cellular and molecular ultrasound imaging. These air-filled, genetically encoded protein nanostructures can be expressed in a variety of cell types to visualize cell location and activity or injected systemically to label and monitor tissue function. Distinguishing GV signal from tissue deep inside intact organisms requires imaging approaches such as amplitude modulation (AM) or collapse-based pulse sequences.

Directed Evolution of Acoustic Reporter Genes Using High-Throughput Acoustic Screening.

A major challenge in the fields of biological imaging and synthetic biology is noninvasively visualizing the functions of natural and engineered cells inside opaque samples such as living animals. One promising technology that addresses this limitation is ultrasound (US), with its penetration depth of several cm and spatial resolution on the order of 100 μm. Within the past decade, reporter genes for US have been introduced and engineered to link cellular functions to US signals heterologous expression in commensal bacteria and mammalian cells.

Harmonic imaging for nonlinear detection of acoustic biomolecules.

Gas vesicles (GVs) based on acoustic reporter genes have emerged as potent contrast agents for cellular and molecular ultrasound imaging. These air-filled, genetically encoded protein nanostructures can be expressed in a variety of cell types to visualize cell location and activity or injected systemically to label and monitor tissue function. Distinguishing GVs from tissue signal deep inside intact organisms requires imaging approaches such as amplitude modulation (AM) or collapse-based pulse sequences, however they have limitations in sensitivity or require irreversible collapse of the GVs that restricts its scope for imaging dynamic cellular processes.

Directed Evolution of Acoustic Reporter Genes Using High-Throughput Acoustic Screening.

A major challenge in the fields of biological imaging and synthetic biology is noninvasively visualizing the functions of natural and engineered cells inside opaque samples such as living animals. One promising technology that addresses this limitation is ultrasound (US), with its penetration depth of several cm and spatial resolution on the order of 100 µm. Within the past decade, reporter genes for US have been introduced and engineered to link cellular functions to US signals via heterologous expression in commensal bacteria and mammalian cells.

Ultrasonic reporters of calcium for deep tissue imaging of cellular signals.

Calcium imaging has enabled major biological discoveries. However, the scattering of light by tissue limits the use of standard fluorescent calcium indicators in living animals. To address this limitation, we introduce the first genetically encoded ultrasonic reporter of calcium (URoC).

Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound.

External control of chemical reactions in biological settings with spatial and temporal precision is a grand challenge for noninvasive diagnostic and therapeutic applications. While light is a conventional stimulus for remote chemical activation, its penetration is severely attenuated in tissues, which limits biological applicability. On the other hand, ultrasound is a biocompatible remote energy source that is highly penetrant and offers a wide range of functional tunability.

Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria.

Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)-one for use in bacteria and one for use in mammalian cells-identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively.

Geometric effects in gas vesicle buckling under ultrasound.

Acoustic reporter genes based on gas vesicles (GVs) have enabled the use of ultrasound to noninvasively visualize cellular function in vivo. The specific detection of GV signals relative to background acoustic scattering in tissues is facilitated by nonlinear ultrasound imaging techniques taking advantage of the sonomechanical buckling of GVs. However, the effect of geometry on the buckling behavior of GVs under exposure to ultrasound has not been studied.

Ultrafast amplitude modulation for molecular and hemodynamic ultrasound imaging.

Ultrasound is playing an emerging role in molecular and cellular imaging thanks to new micro- and nanoscale contrast agents and reporter genes. Acoustic methods for the selective detection of these imaging agents are needed to maximize their impact in biology and medicine. Existing ultrasound pulse sequences use the nonlinearity in contrast agents' response to acoustic pressure to distinguish them from mostly linear tissue scattering.

Self-assembly of protein superstructures by physical interactions under cytoplasm-like conditions.

The structure-driven assembly of multimeric protein complexes and the formation of intracellular phase-like protein condensates have been the subject of intense research. However, the assembly of larger superstructures comprising cellular components, such as protein nanoparticles driven by general physical rather than specific biochemical interactions, remains relatively uncharacterized. Here, we use gas vesicles (GVs)-genetically encoded protein nanoparticles that form ordered intracellular clusters-as a model system to study the forces driving multiparticle assembly under cytoplasm-like conditions.

Ultrasound Technologies for Imaging and Modulating Neural Activity.

Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 μm and 1 ms.

Publisher Correction: Acoustic biosensors for ultrasound imaging of enzyme activity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Acoustic biosensors for ultrasound imaging of enzyme activity.

Visualizing biomolecular and cellular processes inside intact living organisms is a major goal of chemical biology. However, existing molecular biosensors, based primarily on fluorescent emission, have limited utility in this context due to the scattering of light by tissue. In contrast, ultrasound can easily image deep tissue with high spatiotemporal resolution, but lacks the biosensors needed to connect its contrast to the activity of specific biomolecules such as enzymes.

An Online Impedance Analysis and Matching System for Ultrasonic Transducers.

Electrical impedance matching of ultrasonic transducers is important in optimizing the energy consumption as well as guaranteeing equipment safety for ultrasonic systems in both laboratories and industries. The existing solutions usually rely on expensive instruments to conduct off-line impedance measurements and deploying static impedance matching networks for each specific transducer across a target frequency band. Here, we present an initial prototype of an online impedance analysis and matching system (OIAMS).

Experimental Investigation on Graphene Oxide/SrCl₂·6H₂O Modified CaCl₂·6H₂O and the Resulting Thermal Performances.

Although the inorganic salt hydrate phase change materials (PCMs) such as CaCl₂·6H₂O have promising potential for thermal energy storage in building application, the issue of supercooling has restricted their practical application. In this study, graphene oxide (GO) and SrCl₂·6H₂O as binary nucleation agents were used to modify CaCl₂·6H₂O and reduce its supercooling degree. Compared with pure CaCl₂·6H₂O, the incorporation of graphene oxide (GO)/SrCl₂·6H₂O reduced the supercooling degree to 0.