Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid

A new approach has been developed to prepare stable microbubbles (MBs) by interfacial nanoprecipitation of bioabsorbable polymers at air/liquid interfaces. This facile method offers robust control over the morphology and chemophysical properties of MBs by simple chemical modifications. This approach is amenable to large‐scale manufacturing, and is useful to develop functional MBs for advanced biomedical applications. To demonstrate this, a MB‐based intravenous oxygen carrier was created that undergoes pH‐triggered self‐elimination. Intravenous injection of previous MBs increased the risk of pulmonary vascular obstruction. However, we show, for the first time, that our current design is superior, as they 1) yielded no evidence of acute risks in rodents, and 2) improved the survival in a disease model of asphyxial cardiac arrest (from 0 to 100 %), a condition that affects more than 100 000 in‐hospital patients, and carries a mortality of about 90 %.     

One‐Step Microfluidic Coating of Phospholipid Microbubbles with Natural Alginate Polymer as a Delivery System for Human Epithelial Lung Adenocarcinoma

In this study, the neoplastic drug frequently used in the treatment of lung cancer, carboplatin is loaded to microbubbles via a microfluidic platform. In order to increase the drug loading capacity of microbubbles, carboplatin is encapsulated into alginate polymer layer. The phospholipid microbubbles (MBs) are synthesized by MicroSphere Creator, which is connected with T‐junction and micromixer for the treatment with CaCl₂ solution to provide gelation of the alginate coated phospholipid microbubbles (AMBs). The carboplatin loaded alginate coated phospholipid microbubbles (CAMBs) result in 12.2 ± 0.21 µm mean size, obtained by mixing with 0.05% CaCl₂ using T‐junction. The cytotoxic activities of the synthesized MBs, AMBs, and CAMBs are also investigated with the 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) (MTT) and live/dead fluorescent dying assays in the A549 and BEAS‐2B cell lines. The one‐step microfluidic coating of lipid microbubbles with natural alginate polymer appears to be a promising strategy for enhanced drug reservoir properties.     

Magnetic microbubble:A biomedical platform co-constructed from magnetics and acoustics

Generation of magnetic micrbubbles and their basic magnetic and acoustic mechanism are reviewed. The ultrasound （US） and magnetic resonance （MR） dual imaging, the controlled therapeutic delivery, as well as theranostic multifunctions are all introduced based on recent research results. Some on-going research is also discussed.     

Performances of a Pristine Graphene–Microbubble Hybrid Construct as Dual Imaging Contrast Agent and Assessment of Its Biodistribution by Photoacoustic Imaging

Coupling near‐infrared (NIR) nanoscale absorbing materials with microbubbles (MBs) can generate a multifunctional dual imaging contrast agent. A new approach is presented for a hybrid photoacoustic/ultrasound contrast enhancer where pristine graphene is stably tethered to poly(vinyl alcohol) (PVA)‐based MBs. The main advantages of this approach are i) the preservation of optical and mechanical properties of intact graphene for an efficient photoacoustic (PA) enhancement and ii) the echogenicity and biocompatibility due to the robust anchoring of graphene to the bioinert PVA shell. PVA MBs provide ideal platforms for drug loading and ligand tethering for specific tumor targeting. One of the crucial goals toward this direction is optimizing this system in terms of balance between favorable acoustic/photoacoustic properties, immune shielding, and cytotoxicity. Such a combination strongly depends on the bridging moieties between graphene and the microbubble surface and can be easily tuned by PEGylation. The optimized graphene PVA MBs as contrast agent provide an efficient enhancement in vivo both in ultrasound and photoacoustic modes. The spectrally separable absorbance profile allows to a first demonstration of performing real‐time in vivo multiplexed photoacoustic imaging of graphene PVA MBs, and assessment of their full body biodistribution using a Vevo LAZR‐X photoacoustic imaging system.     

Quantitative Screening of Cell‐Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection

A screening strategy involving designed extractors and collectors was used for the nondestructive quantitation of gangliosides on cell surfaces. The extractors were constructed by functionalizing maleimide silica bubbles with a DNA probe, which contains an endonuclease cleavage site and a boronic acid end to extract cell‐surface sialic acid‐containing compounds through simple centrifugation. After the extractors containing the extracted compounds were incubated with endonuclease, the released oligonucleotide‐gangliosides were selectively collected by silanized collector bubbles through hydrophobic interactions. The in vitro fluorescent signals from the collectors were used for the quantitation of cell‐surface gangliosides. By combining with sialidase cleavage, a protocol for the identification of ganglioside subtypes was developed. The successful monitoring of the regeneration of cell‐surface gangliosides demonstrates the potential of this strategy in probing related biological processes.     

Recruitment and Immobilization of a Fluorinated Biomarker Across an Interfacial Phospholipid Film using a Fluorocarbon Gas

Perfluorohexane gas when introduced in the air atmosphere above a film of phospholipid self‐supported on an aqueous solution of C₂F₅‐labeled compounds causes the recruitment and immobilization of the latter in the interfacial film. When the phospholipid forms a liquid‐condensed Gibbs monolayer, which is the case for dipalmitoylphosphatidylcholine (DPPC), the C₂F₅‐labeled molecule remains trapped in the monolayer after removal of F‐hexane. Investigations involve bubble profile analysis tensiometry (Gibbs films), Langmuir monolayers and microbubble experiments. The new phenomenon was utilized to incorporate a hypoxia biomarker, a C₂F₅‐labeled nitrosoimidazole (EF5), in microbubble shells. This finding opens perspectives in the delivery of fluorinated therapeutic molecules and biomarkers.     

多层膜磁性微泡的非线性声振动特性

超顺磁性氧化铁纳米粒子与造影剂微泡结合形成磁性微泡,用于产生多模态造影剂,以增强医学超声和磁共振成像.将装载有纳米磁性颗粒的微泡包膜层看作由磁流体膜与磷脂膜组合而成的双层膜结构,同时考虑磁性纳米颗粒体积分数a对膜密度及黏度的影响,从气泡动力学基本理论出发,构建多层膜结构磁性微泡非线性动力学方程.数值分析了驱动声压和频率等声场参数、颗粒体积分数、膜层厚度以及表面张力等膜壳参数对微泡声动力学行为的影响.结果表明,当磁性颗粒体积分数较小且a≤0.1时,磁性微泡声响应特性与普通包膜微泡相似,微泡的声频响应与其初始尺寸和驱动压有关;当驱动声场频率f为磁性微泡共振频率f0的2倍(f=2f0)时,微泡振动失稳临界声压最低;磁性颗粒的存在抑制了泡的膨胀和收缩但抑制效果非常有限;磁性微泡外膜层材料的表面张力参数K及膜层厚度d也会影响微泡的振动,当表面张力参数及膜厚取值分别为0.2—0.4 N/m及50—150 nm时,可观察到气泡存在不稳定振动响应区.     

Improvement of the axial trapping effect using azimuthally polarised trapping beam

A dual optical tweezers system,which consists of a doughnut mode optical tweezer (DMOT) with the azimuthally polarised trapping beam and a solid mode optical tweezer (SMOT) with the Gauss trapping beam was constructed to compare the axial trapping effect of DMOT and SMOT.The long-distance axial trapping of ST68 microbubbles (MBs) achieved by DMOT was more stable than that of SMOT.Moreover the axial trapping force measured using the viscous drag method,was depended on the diameter of the particle,the laser power,and the numerical aperture (NA) of the objective lens.The measurement of the axial trapping force and the acquisition of CCD images of trapping effect confirmed that the DMOT showed excellent axial trapping ability than SMOT.A simple and effective method is developed to improve axial trapping effect using the azimuthally polarized beam as trapping beam.This is helpful for the long-distance manipulating of particles especially polarised biological objects in axial direction.     

Magnetic Resonance Detection of Gas Microbubbles via HyperCEST: A Path Toward Dual Modality Contrast Agent

Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful magnetic resonance (MR) intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules (concentrations well below the NMR detection threshold) that exchange hyperpolarized ¹²⁹Xe. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of ¹²⁹Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.