Accessing the spatiotemporal heterogeneities of single nanocatalysts by optically imaging gas nanobubbles

Catalysts that catalyze the generation of products in the gas phase, especially those involved in the hydrogen evolution reaction (HER), hold great promise for ecofriendly and sustainable energy development. In general, gas chromatography is widely used to measure catalytic activity. Unfortunately, it gives an averaged output that washes out the heterogeneities among individuals. To assess the unique catalytic properties at the single nanoparticle level, various methods based on single particle catalysis have been proposed. Over the past fifteen years, tremendous breakthroughs have been achieved, which uncovered hidden spatial and temporal heterogeneities. Although powerful, effectively quantifying the activities of single HER nanocatalysts remains challenging because of the fast diffusion of hydrogen (H₂). In 2017, a novel approach based on a nanobubble indicator was proposed to correlate the kinetics of gas bubble evolution with the catalytic activities of individual nanoentities during the HER process. Since then, a plethora of optical microscopy techniques have been utilized to monitor dynamically evolved nanobubbles and to measure the catalytic activities of single HER catalysts. In this minireview, we summarized state-of-the-art optical microscopy for in operando imaging of dynamic nanobubbles involved in gas-generating reactions while highlighting some important discoveries, including the blinking photocatalytic activity and heterogeneous distribution of active sites. Finally, challenges and future perspectives in this promising field were identified.     

Differentiating bulk nanobubbles from nanodroplets and nanoparticles

History has shown that it is not as easy as one might think to differentiate between bulk nanobubbles and nanodroplets or nanoparticles. It is generally easy to detect colloids (i.e. something that looks different, e.g. scatters light differently than its surrounding solvent), but less easy to determine the nature of these colloids. This has led to misinterpretations in the literature, where nanodroplets or nanoparticles have mistakenly been assumed to be nanobubbles. In this paper, we review a multitude of experimental methods and approaches to prove the existence of bulk nanobubbles. We conclude that combinations of optical detection with physical perturbations such as pressure or ultrasound, or phase-sensitive holographic methods are the most promising and convenient approaches.     

Direct measurement of weak depletion force between two surfaces

In a mixture of colloidal particles and polymer molecules,the particles may experience an attractive"depletion force"if the size of the polymer molecule is larger than the interparticle separation.This is because individual polymer molecules experience less conformational entropy if they stay between the particles than they escape the inter-particle space, which results in an osmotic pressure imbalance inside and outside the gap and leads to interparticle attraction.This depletion force has been the subject of several studies since the 1980s,but the direct measurement of this force is still experimentally challenging as it requires the detection of energy variations of the order of k_BT and beyond.We present here our results for applying total internal reflection microscopy(TIRM) to directly measure the interaction between a free-moving particle and a flat surface in solutions consisting of small water-soluble organic molecules or polymeric surfactants.Our results indicate that stable nanobubbles(ca.150 nm) exist free in the above aqueous solutions.More importantly,the existence of such nanobubbles induces an attraction between the spherical particle and flat surface.Using TIRM,we are able to directly measure such weak interaction with a range up to 100 nm.Furthermore,we demonstrate that by employing thermo-sensitive microgel particles as a depleting agent,we are able to quantitatively measure and reversibly control k_BYT-scale depletion attraction as function of solution pH.     

Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique.     

Leveraging re-chargeable nanobubbles on amine-functionalized ZnO nanocrystals for sustained ultrasound cavitation towards echographic imaging

Nanoparticles able to promote inertial cavitation when exposed to focused ultrasound have recently gained much attention due to their vast range of possible applications in the biomedical field, such as enhancing drug penetration in tumor or supporting ultrasound contrast imaging. Due to their nanometric size, these contrast agents could penetrate through the endothelial cells of the vasculature to target tissues, thus enabling higher imaging resolutions than commercial gas-filled microbubbles. Herein, Zinc Oxide NanoCrystals (ZnO NCs), opportunely functionalized with amino-propyl groups, are developed as novel nanoscale contrast agents that are able, for the first time, to induce a repeatedly and over-time sustained inertial cavitation as well as ultrasound contrast imaging. The mechanism behind this phenomenon is investigated, revealing that re-adsorption of air gas nanobubbles on the nanocrystal surface is the key factor for this re-chargeable cavitation. Moreover, inertial cavitation and significant echographic signals are obtained at physiologically relevant ultrasound conditions (MI < 1.9), showing great potential for low side-effects in in-vivo applications of the novel nanoscale agent from diagnostic imaging to gas-generating theranostic nanoplatforms and to drug delivery.     

Stability of surface and bulk nanobubbles

The existence of stable nanoscopic gaseous domains in liquids, or nanobubbles, has attracted both skepticism and intrigue since classical theory predicts that spherical gas bubbles cannot achieve stable equilibrium. Can we prove these gaseous domains exist, and if they do, how do they survive? We critically review contemporary theoretical perspectives of the stability of surface and bulk nanobubbles and explain how experiments either vindicate or disprove them. We conclude with a discussion of unanswered questions and propose future directions for the field at large.     

Bursting microbubbles: How nanobubble contrast agents can enable the future of medical ultrasound molecular imaging and image-guided therapy

The field of medical ultrasound has undergone a significant evolution since the development of microbubbles as contrast agents. However, because of their size, microbubbles remain in the vasculature and therefore have limited clinical applications. Building a better—and smaller—bubble can expand the applications of contrast-enhanced ultrasound by allowing bubbles to extravasate from blood vessels—creating new opportunities. In this review, we summarize recent research on the formulation and use of nanobubbles (NBs) as imaging agents and as therapeutic vehicles. We discuss the ongoing debates in the field and reluctance to accepting NBs as an acoustically active construct and a potentially impactful clinical tool that can help shape the future of medical ultrasound. We hope that the overview of key experimental and theoretical findings in the NB field presented in this article provides a fundamental framework that will help clarify NB–ultrasound interactions and inspire engagement in the field.     

Electrokinetic potential reduction of fine particles induced by gas nucleation

Electrokinetic potential of particles has been extensively studied in colloidal systems over the past century, while up to date, the influence of gas on electrokinetic behaviors of particles has not been fully understood yet. In this study, the electrokinetic response of particles to gas nucleation was systematically investigated with coal as the object. The results showed that the nucleation of gas (both on particle surfaces and in water) significantly changed the particle’ electrokinetic behaviors. Higher gas content and particle’s surface hydrophobicity normally trigger more intensive gas nucleation, thus inducing more significant reduction of particle zeta potential. After gas nucleation, numerous nanobubbles (NBs) appear in the suspensions mainly in two forms: NBs adhering onto solid surfaces (ANBs) and NBs stagnating in bulk solutions (BNBs). ANBs not only enhance the surface heterogeneity, but also cause the “steric hindrance” effect, and electric double layer (EDL) overlapping and associated ions shielding towards charged particles, which significantly decrease their electrokinetic potentials. Although BNBs can also reduce the zeta potential of particles by EDL compressing, their functions are rather limited.     

Nanobubbles for therapeutic delivery: Production,stability and current prospects

Nanobubbles (NBs) have recently garnered widespread attention for their potential use as dual diagnostic and therapeutic agents. Similar to their micron-sized relatives (microbubbles), NBs are shell-stabilized, gas-cored bubbles that in conjunction with ultrasound can be used to increase imaging contrast, as well as provide a mechanism for trigger drug release and increased therapeutic delivery.In this review, we specifically focus on their development as agents to enhance drug delivery, discussing theory, characterization techniques, key formulations and prospects for translation into clinical use.