Manipulating nanoscale features on the surface of dye-loaded microbubbles to increase their ultrasound-modulated fluorescence output.

The nanoscale surface features of lipid-coated microbubbles can dramatically affect how the lipids interact with one another as the microbubble diameter expands and contracts under the influence of ultrasound. During microbubble manufacturing, the different lipid shell species naturally partition forming concentrated lipid islands. In this study the dynamics of how these nanoscale islands accommodate the expansion of the microbubbles are monitored by measuring the fluorescence intensity changes that occur as self-quenching lipophilic dye molecules embedded in the lipid layer change their distance from one another. It was found that when the dye molecules were concentrated in islands, less than 5% of the microbubbles displayed measurable fluorescence intensity modulation indicating the islands were not able to expand sufficiently for the dye molecules to separate from one another. When the microbubbles were heated and cooled rapidly through the lipid transition temperature the islands were melted creating an even distribution of dye about the surface. This resulted in over 50% of the microbubbles displaying the fluorescence-modulated signal indicating that the dye molecules could now separate sufficiently to change their self-quenching efficiency. The separation of the surface lipids in these different formations has significant implications for microbubble development as ultrasound and optical contrast agents.

Phospholipid/Carbocyanine Dye-Shelled Microbubbles as Ultrasound-Modulated Fluorescent Contrast Agents.

Fluorescent microbubbles have been fabricated with the capacity to have their emission modulated by ultrasound. These contrast agent particles could potentially be used in the future to extract fluorescence modulation from a strong light background to increase imaging depth and resolution in scattering media. Fluorescence intensity modulation was demonstrated at the ultrasound driving frequency.

Characterization of individual ultrasound microbubble dynamics with a light-scattering system.

Ultrasound microbubbles are contrast agents used for diagnostic ultrasound imaging and as carriers for noninvasive payload delivery. Understanding the acoustic properties of individual microbubble formulations is important for optimizing the ultrasound imaging parameters for improved image contrast and efficient payload delivery. We report here a practical and simple optical tool for direct real-time characterization of ultrasound contrast microbubble dynamics based on light scattering. Fourier transforms of raw linear and nonlinear acoustic oscillations, and microbubble cavitations are directly recorded. Further, the power of this tool is demonstrated by comparing clinically relevant microbubble cycle-to-cycle dynamics and their corresponding Fourier transforms.

Facile One-Pot Synthesis of Polymer-Phospholipid Composite Microbubbles with Enhanced Drug Loading Capacity for Ultrasound-Triggered Therapy.

This paper reports the one-pot synthesis of perfluorocarbon microbubbles with crosslinked shells of poly(acrylic acid) and phospholipid that boast excellent ultrasound contrast enhancement, enhanced loading capacity, and the ability to retain or release their contents through variation in the level of ultrasound exposure.

Performance trade-offs in single-photon avalanche diode miniaturization.

Single-photon avalanche diodes (SPADs) provide photons' time of arrival for various applications. In recent years, attempts have been made to miniaturize SPADs in order to facilitate large-array integration and in order to reduce the dead time of the device. We investigate the benefits and drawbacks of device miniaturization by characterizing a new fast SPAD in a commercial 0.18 microm complementary metal oxide semiconductor technology. The device employs a novel and efficient guard ring, resulting in a high fill factor. Thanks to its small size, the dead time is only 5 ns, resulting in the fastest reported SPAD to date. However, the short dead time is accompanied by a high after-pulsing rate, which we show to be a limiting parameter for SPAD miniaturization. We describe a new and compact active-recharge scheme which improves signal-to-noise tenfold compared with the passive configuration, using a fraction of the area of state-of-the-art active-recharge circuits, and without increasing the dead time. The performance of compact SPADs stands to benefit such applications as high-resolution fluorescence-lifetime imaging, active-illumination three-dimensional imagers, and quantum key distribution systems.