Generation of bubbles is disclosed to occur within a flow of an aqueous fluid. The bubbles may be formed within a tube of a selected diameter and the bubbles are controlled to exit the tube at a selected diameter. Generally, bubbles are formed to include a diameter of less than 1 millimeter, including less than about 20 microns.

Disclosed herein are a microbubble-extracellular vesicle complex, a production method therefor, and a system for driving the same. In one aspect, preferred microbubble-extracellular vesicle complexes may comprise an ultrasound contrast agent-based microbubble, an extracellular cell derived from a natural killer cell (NK cell), a human glial cell, or a human mesenchymal stem cell, and a coupling medium and can be derive in a 3D mode using ultrasonic waves and deliver a drug loaded in the extracellular vesicle to a target site.

The invention provides, inter alia, improved lipid formulations used to generate lipid-encapsulated gas microspheres, and methods of their use.

The invention discloses a recombinant protein (P-selectin glycoprotein ligand-1 and Neural Retina-specific Leucine Zipper) PSGL-1-NRL chimeric protein comprising a Selectin Binding domain and a non-covalent dimerization domain, which is a leucine zipper and is more preferably the leucine zipper domain of the human or mouse Neural Retina-specific Leucine Zipper. The chimeric protein further comprises a covalent dimerization domain with at least one cysteine suitable to form a disulfide bridge with another chimeric protein to form a homodimer.

In the chimeric protein, the PSGL-1 domain corresponds to the extracellular region of Human PSGL-1 and is more preferably the selectin binding region of the mature protein.

The chimeric protein is correctly post-translationally modified and is efficiently expressed in a mammalian system. It is sulfated, O-linked glycosylated and sialylated and binds P, E and L selectin, allowing in vivo and in vitro targeting for diagnostic or therapeutic purposes.

Provided herein are improved methods for preparing phospholipid formulations including phospholipid UCA formulations.

Ultrasound imaging is a non-invasive, non-radioactive, and low cost technology for diagnosis and identification of implantable medical devices in real time. Developing new ultrasound activated coatings is important to broaden the utility of in vivo marking by ultrasound imaging. Ultrasound responsive macro-phase segregated micro-composite thin films were developed to be coated on medical devices composed of multiple materials and with multiple shapes and varying surface area. The macro-phase segregated in films having silica micro-shells in polycyanoacrylate produces strong color Doppler signals with the use of a standard clinical ultrasound transducer. Electron microscopy showed a macro-phase separation during slow curing of the cyanoacrylate adhesive, as air-filled silica micro-shells were driven to the surface of the film. The air sealed in the hollow space of the silica shells acted as an ultrasound contrast agent and echo decorrelation of air exposed to ultrasound waves produces color Doppler signals.

Provided herein are genetically engineered gas vesicle expression systems (GVES) that are configured to express gas vesicles (GVs) in a mammalian cell, related gas vesicle polynucleotide constructs, gas vesicle reporting genetic circuits, vectors, genetically engineered mammalian cells, non-human mammalian hosts, compositions, methods and systems, which in several embodiments can be used together with contrast-enhanced imaging techniques to detect and report biological events in an imaging target site comprising a mammalian cell and/or organism.

The present disclosure includes system, methods, and kits relating to creating a second structure with a plurality of first structures at a target site inside or adjacent to a host object. The methods include the step of generating a field that non-invasively penetrates into the host object. The methods further include the step of positioning a first portion of the plurality of first structures at the target site using a force corresponding to the field. Additionally, the methods include the step of linking the first portion of the plurality of first structures with one another and/or the host object at the target site to form the second structure.

The present invention provides oxygenized nanobubbles and their uses in imaging and cancer treatment when combined with therapeutic drugs and precise ultrasound beam steering.

The present disclosure relates to a method of imaging, involving administration of a bi-phasic formulation followed by application of high frequency sound waves to identify a region of interest. Following identification, a phase shift of the bi-phasic formulation may be activated by a second administration of high frequency sound waves such that gaseous components of the bi-phasic formulation are enlarged and localised at the region of interest.