Columbia University

University of Colorado

The University of North Carolina at Chapel Hill

The University of Arizona

Children's Medical Center Corporation

Board of Regents of the University of Nebraska

Massachusetts Institute of Technology

Mark A Borden

Terry Onichi Matsunaga

Paul Alexander Dayton

Paul Steven Sheeran

Elisa E Konofagou

Clark T Hung

Eric G Lima

Benjamin S Terry

Edward J Swanson

Shashank Ramesh Sirsi

Daniel S Kohane

John N Kheir

James J Choi

Hila Epstein-Barash

Jameel A Feshitan

Fotios Vlachos

Francis X McGowan

A system and methods for the delivery of oxygen through a body cavity of a subject using oxygen microbubbles. Through circulation of oxygen microbubbles through the body cavity, oxygen and carbon dioxide exchange may occur. Overall improvement in extending survival rate time during emergency situations caused by pulmonary or similar oxygen-intake restricting injury and/or failure may be achieved through use of the invented system and methods.

Systems and methods for ventilation through a body cavity

Acoustically activatable particles having low vaporization energy are disclosed. A particle of material includes a first substance that includes at least one component that has a boiling point below 25&#xb0; C. at atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create the particle. The particle has a core consisting of a liquid and is an activatable phase change agent. The second substance includes a polymeric brush layer to prevent aggregation and coalescence.

Formulation of acoustically activatable particles having low vaporization energy and methods for using same

An acoustically activatable particle of material includes a first substance that includes a component that is a gas 25&#xb0; C. and atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure. At least some of the first substance exists in a gaseous phase at the time of encapsulation of the first substance within the second substance to form a bubble. After formation of the bubble, the bubble is condensed into a liquid phase, which causes the bubble to transform into the droplet or emulsion having a core consisting of a liquid. The droplet or emulsion is an activatable phase change agent having a core consisting of a liquid at 25&#xb0; C. and atmospheric pressure. The first substance has a boiling point below 25&#xb0; C. at atmospheric pressure.

System and methods for ventilation through a body cavity

Gas-filled microbubbles can be synthesized using a continuous flow chamber and a sonicator. The resulting microbubble solution can be size-sorted for a particular application, such as injection into a patient for gas delivery thereto. The microbubble solution may be concentrated to have greater than 50% volume gas while maintaining microbubble sizes below 10 &#x3bc;m. Control of the microbubble generation process can yield highly stable microbubbles. The microbubbles may retain over half of their original gas payload for over three weeks while exhibiting minimal change in microbubble size. The systems, methods, and devices described herein thus allow for continuous or batch-wise continuous production of gas-filled microbubbles that readily release their gas payload when introduced into an under-saturated or de-saturated solution.

Systems, methods, and devices for production of gas-filled microbubbles

Injectable or implantable drug delivery systems providing on-demand ultrasound-triggered drug release and methods for controlling the release of drug in a patient are provided herein. The on-demand drug delivery systems contain a drug depot and a drug encapsulated in an encapsulating material, where the encapsulating material is different from the depot. In the preferred embodiment, the depot also contains microbubbles that encapsulate one or more gases. The microbubbles enhance the drug release when ultrasound is applied compared to the same system in the absence of microbubbles. In a preferred embodiment, the drug delivery system, contains an encapsulating material, preferably liposomes, a drug to be delivered, microbubbles, and at least two hydrogel-forming precursor components. Following injection or implantation, the patient can control the time, location and dosage released by administering ultrasound.

Composition for on-demand ultrasound-triggered drug delivery

A hydrogel tissue engineering scaffold having microbubbles dispersed therein is disclosed. Also, a system for cell culturing including a controller and actuator to apply dynamic deformational loading to a hydrogel is disclosed. Also disclosed are methods for producing hydrogels with microbubbles and for culturing cells using hydrogels with microbubbles.

Microbubble devices, methods and systems

A method of producing particles of materials includes, with a first substance that includes at least one component that is a gas at room temperature and atmospheric pressure, extruding or emulsifying the first substance into or in the presence of a second substance to create a bubble in which the first substance is encapsulated by the second substance and wherein at least some of the first substance is in a gaseous phase, and causing the first substance to condense to a liquid phase, which causes the bubble to transform into a droplet or emulsion. The droplet or emulsion so created is an activatable phase change agent that is stable at room temperature and pressure.

Systems and methods for opening a tissue to a target value are disclosed herein. In an exemplary method, a region of the tissue is targeted for opening, a size range of microbubbles corresponding to the target value is determined, microbubbles of the size range are positioned in proximity to the targeted region, and an ultrasound beam is applied to the targeted region such that the tissue is opened with the assistance of the microbubbles to the target value.

Systems and methods for opening a tissue

Systems, methods, and devices for generating and using size-selected lanthanide-coated microbubbles for controlling an imaging signal via microbubble fragmentation and for magnetic resonance imaging guided focused ultrasound therapy.

Medical imaging contrast devices, methods, and systems

A suspension of gas-filled microbubbles can be synthesized by sonicating a lipid solution and a first gas in a reaction volume. The resulting microbubble suspension can be stored for later use, for example, for infusion into a patient for gas delivery thereto. Various techniques can improve the shelf life of the microbubbles. For example, the microbubble suspension can be freeze-dried to remove water and the first gas therefrom while leaving the microbubble shells intact. In an alternative, the microbubble suspension can be frozen. In still another alternative, the microbubble suspension can be formed with a first gas that has a low solubility, thereby creating microbubbles with increased stability. Prior to use, the microbubble suspension can be prepared by exchanging the gas in the microbubble cores, rehydrating, and/or raising the temperature of the stored microbubbles.

Systems, methods, and devices for microbubbles

Compositions containing a carrier and microbubbles encapsulating one or more gases, preferably oxygen, and methods for making and using the compositions are described herein. The microbubbles contain a lipid envelope. The compositions may be administered to a patient to quickly deliver large amounts of oxygen to the patient's blood supply or directly to a tissue in need of oxygen. The compositions may be administered via injection or as a continuous infusion. The compositions contain a concentrated microbubble suspension, where the suspension contains at least 40 mL oxygen/dL suspension. The microbubbles are preferably less than 20 microns in diameter, more preferably less than 15 microns in diameter. The microbubbles described herein may be administered to a patient in an effective amount to increase in oxygen concentration in the patient's blood, and/or one or more tissues or organs.

Growing community of inventors

Boulder, CO, United States of America

Mark A Borden