Transient Adsorption Behavior of Single Fluorophores on an Electrode-Supported Nanobubble.

Here we report the use of a Langmuir isotherm model to analyze and better understand the dynamic adsorption and desorption behavior of single fluorophore molecules at the surface of a hydrogen nanobubble supported on an indium tin oxide (ITO) electrode. Three rhodamine dyes, rhodamine 110 (R110, positively charged), rhodamine 6G (R6G, positively charged), and sulforhodamine G (SRG, negatively charged) were chosen for this study. The use of the Langmuir isotherm model allows us to determine the equilibrium constant and the rate constants for the adsorption and desorption processes. Of the three fluorophores used in this study, SRG was found to have the greatest equilibrium constant. No significant potential dependence was observed on the adsorption characteristics, which suggests the nanobubble size, geometry, and surface properties are relatively constant within the range of potentials used in this study. Our results suggest that the use of the Langmuir isotherm model is a valid and useful means for probing and better understanding the unique adsorption behavior of fluorophores at surface-supported nanobubbles.

Nanobubble Labeling and Imaging with a Solvatochromic Fluorophore Nile Red.

Herein, we report the use of a polarity-sensitive, solvatochromic fluorophore Nile red to label and probe individual hydrogen nanobubbles on the surface of an indium-tin oxide (ITO) electrode. Nanobubbles are generated from the reduction of water on ITO and fluorescently imaged from the transient adsorption and desorption process of single Nile red molecules at the nanobubble surface. The ability to label and fluorescently image individual nanobubbles with Nile red suggests that the gas/solution interface is hydrophobic in nature. Compared to the short labeling events using rhodamine fluorophores, Nile red-labeled events appear to be longer in duration, suggesting that Nile red has a higher affinity to the bubble surface. The stronger fluorophore-bubble interaction also leads to certain nanobubbles being co-labeled by multiple Nile red molecules, resulting in the observation of super-bright and long-lasting labeling events. Based on these interesting observations, we hypothesize that Nile red molecules may start clustering and form some kind of molecular aggregates when they are co-adsorbed on the same nanobubble surface. The ability to observe super-bright and long-lasting multifluorophore labeling events also allows us to verify the high stability and long lifetime of electrochemically generated surface nanobubbles.

Single-Molecule Fluorescence Microscopy for Probing the Electrochemical Interface.

The electrochemical interface is an ultrathin interfacial region between the electrode and solution where electrochemical reactions occur. The study of the electrochemical interface continues to be one of the most exciting directions in modern electrochemistry research. Much of our existing knowledge about the electrochemical interface comes from ensemble measurements and ex situ imaging of the electrode surface. Due to its enormous complexity and highly dynamic nature, however, new imaging tools that can probe the interface in situ with ultrahigh spatial and temporal resolution and single-molecule sensitivity are apparently needed. Single-molecule fluorescence microscopy (SMFM) has emerged as a powerful tool that is uniquely suited for studying the electrochemical interface. In this mini-review, we first give a brief overview of various existing SMFM methods for studying electrochemical problems. We then discuss several exciting research topics involving the use of SMFM methods for studying surface-immobilized molecules, single freely diffusing molecules, single molecules as catalytic reaction indicators, and single-molecule labeling and imaging of interfacial nanobubbles. We anticipate that we will continue to see a rapid increase in publications on stochastic electrochemistry of single molecules and nanoparticles. The increased use of SMFM will likely bring new information to our study of the electrochemical interface.

Collision and Coalescence of Single Attoliter Oil Droplets on a Pipet Nanopore.

We describe the use of a quartz pipet nanopore to study the collision and coalescence of individual emulsion oil droplets and their subsequent nanopore translocation. Collision and coalescence of single toluene droplets at a nanopore orifice are driven primarily by electroosmosis and electrophoresis and lead to the fast growth of a trapped oil droplet. This results in a stepwise current response due to the coalesced oil droplet increasing its volume and its ability to partially block the nanopore's ionic current, allowing us to use the resistive-pulse method to resolve single droplet collisions. Further growth of the trapped oil droplet leads to a complete blockage of the nanopore and a nearly 100% current decay. The trapped oil droplet shows enormous mechanical stability at lower voltages and stays in its trapped status for hundreds of seconds. An increased voltage can be used to drive the trapped droplet into the pipet pore within several milliseconds. Simultaneous fluorescence imaging and amperometry were performed to examine droplet collision, coalescence, and translocation, further confirming the proposed mechanism of droplet-nanopore interaction. Moreover, we demonstrate the unique ability to perform fast voltammetric measurements on a nanopore-supported attoliter oil droplet and study its voltage-driven ion transfer processes.

Anti-Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated anti-programmed cell death (PD)-1 immunotherapy (nivolumab or pembrolizumab) for overall efficacy, safety, and effective dose relative to standard chemotherapy or other conventional drugs in the treatment of malignant tumors. We searched the following databases, PubMed, Medline, Embase, Cochrane, Wangfang Data, Weipu, and China National Knowledge Infrastructure, and the reference lists of the selected articles for randomized controlled trials (RCTs) of anti-PD-1 therapies in humans. The outcome measures were overall survival, treatment response, and adverse events. Only four randomized controlled trials met our inclusion criteria. Three of these evaluated responses to nivolumab, whereas one tested pembrolizumab. The result of our analysis suggested that nivolumab may improve the overall response rate in treating melanoma relative to chemotherapy and has few associated adverse events. Similarly, in metastatic melanoma patients, nivolumab had a significant advantage over dacarbazine in terms of 1-year survival, progression-free survival, and objective response rate. Regarding dose levels of nivolumab for patients with metastatic renal cell carcinoma, the outcomes in response to 2 and 10 mg/kg were similar, but both had significant advantages over 0.3 mg/kg. In addition, pembrolizumab showed similar outcomes in response to 2- and 10-mg/kg treatment. Anti-PD-1 immunotherapy appears to be safe and effective for patients with melanoma or metastatic renal cell carcinoma. Our meta-analysis is limited, but additional clinical trials are warranted to verify this preliminary evidence of positive outcomes and before anti-PD-1 therapy can be recommended for routine clinical use.