The application of single molecule nanopore sensing for quantitative analysis

Nanopore-based sensors typically work by monitoring transient pulses in conductance via current-time traces as molecules translocate through the nanopore. The unique property of being able to monitor single molecules gives nanopore sensors the potential as quantitative sensors based on the counting of single molecules. This review provides an overview of the concepts and fabrication of nanopore sensors as well as nanopore sensing with a view toward using nanopore sensors for quantitative analysis. We first introduce the classification of nanopores and highlight their applications in molecular identification with some pioneering studies. The review then shifts focus to recent strategies to extend nanopore sensors to devices that can rapidly and accurately quantify the amount of an analyte of interest. Finally, future prospects are provided and briefly discussed. The aim of this review is to aid in understanding recent advances, challenges, and prospects for nanopore sensors for quantitative analysis

Light Hadron Spectroscopy and Decay at BESIII

Light hadron spectroscopy plays an important role in understanding the decay dynamics of unconventional hadronic states, such as strangeonium and glueballs. BESIII provides an ideal avenue to search for these exotic states thanks to a huge amount of data recorded at various energy points in the tau-charm mass region including J/psi resonance. This report summarizes recent results of the BESIII experiment related to the glueballs and strangeonium-like states.Comment: 6 pages, 5 figures, Conference proceeding of FPCP-201

Optical Nanopore Sensors for Quantitative Analysis

Nanopore sensors have received significant interest for the detection of clinically important biomarkers with single-molecule resolution. These sensors typically operate by detecting changes in the ionic current through a nanopore due to the translocation of an analyte. Recently, there has been interest in developing optical readout strategies for nanopore sensors for quantitative analysis. This is because they can utilize wide-field microscopy to independently monitor many nanopores within a high-density array. This significantly increases the amount of statistics that can be obtained, thus enabling the analysis of analytes present at ultralow concentrations. Here, we review the use of optical nanopore sensing strategies for quantitative analysis. We discuss optical nanopore sensing assays that have been developed to detect clinically relevant biomarkers, the potential for multiplexing such measurements, and techniques to fabricate high density arrays of nanopores with a view toward the use of these devices for clinical applications

Spiers Memorial Lecture. Next generation nanoelectrochemistry: the fundamental advances needed for applications

Nanoelectrochemistry, where electrochemical processes are controlled and investigated with nanoscale resolution, is gaining more and more attention because of the many potential applications in energy and sensing and the fact that there is much to learn about fundamental electrochemical processes when we explore them at the nanoscale. The development of instrumental methods that can explore the heterogeneity of electrochemistry occurring across an electrode surface, monitoring single molecules or many single nanoparticles on a surface simultaneously, have been pivotal in giving us new insights into nanoscale electrochemistry. Equally important has been the ability to synthesise or fabricate nanoscale entities with a high degree of control that allows us to develop nanoscale devices. Central to the latter has been the incredible advances in nanomaterial synthesis where electrode materials with atomic control over electrochemically active sites can be achieved. After introducing nanoelectrochemistry, this paper focuses on recent developments in two major application areas of nanoelectrochemistry; electrocatalysis and using single entities in sensing. Discussion of the developments in these two application fields highlights some of the advances in the fundamental understanding of nanoelectrochemical systems really driving these applications forward. Looking into our nanocrystal ball, this paper then highlights: the need to understand the impact of nanoconfinement on electrochemical processes, the need to measure many single entities, the need to develop more sophisticated ways of treating the potentially large data sets from measuring such many single entities, the need for more new methods for characterising nanoelectrochemical systems as they operate and the need for material synthesis to become more reproducible as well as possess more nanoscale control

Development of bidding strategies in electricity markets using possibility theory

In the electricity market environment, bidding strategies employed by generation companies may have significant impacts on their own benefits, and on the operating behaviors of an electricity market as well. Hence, how to develop optimal bidding strategies for generation companies or how to analyze strategic behaviors of them and hence to figure out the potential market power abuse is now a very active research area. A possibility theory based approach is proposed in this work for building optimal bidding strategies for generation companies. Based on historical bidding data, the available (production cost) data before the power industry restructuring and experts' heuristic knowledge, the well-known fuzzy set theory is employed to represent the estimated bidding behaviors of rival generation companies, and a fuzzy programming model is developed and a solution method follows. The approach is especially suitable for those electricity markets recently launched, since sufficient historical bidding data is not available and hence probability methods cannot be employed. Finally, a sample example with six generation companies participating in an electricity market is served for demonstrating the essential features of the presented approach.published_or_final_versio

Rapid and ultrasensitive electrochemical detection of circulating tumor DNA by hybridization on the network of gold-coated magnetic nanoparticles

An accurate and robust method for quantifying the levels of circulating tumor DNA (ctDNA) is vital if this potential biomarker is to be used for the early diagnosis of cancer. The analysis of ctDNA presents unique challenges because of its short half-life and ultralow abundance in early stage cancers. Here we develop an ultrasensitive electrochemical biosensor for rapid detection of ctDNA in whole blood. The sensing of ctDNA is based on hybridization on a network of probe DNA modified gold-coated magnetic nanoparticles (DNA-Au@MNPs). This DNA-Au@MNPs biosensor can selectively detect short- and long-strand DNA targets. It has a broad dynamic range (2 aM to 20 nM) for 22 nucleotide DNA target with an ultralow detection limit of 3.3 aM. For 101 nucleotide ctDNA target, a dynamic range from 200 aM to 20 nM was achieved with a detection limit of 5 fM. This DNA-Au@MNPs based sensor provides a promising method to achieve 20 min response time and minimally invasive cancer early diagnosis

Key Parameters That Determine the Magnitude of the Decrease in Current in Nanopore Blockade Sensors

Nanopore blockade sensors were developed to address the challenges of sensitivity and selectivity for conventional nanopore sensors. To date, the parameters affecting the current of the sensor have not been elucidated. Herein, the impacts of nanopore size and charge and the shape, size, surface charge, and aggregation state of magnetic nanoparticles were assessed. The sensor was tolerant to all parameters contrary to predictions from electronic or geometric arguments on the current change. Theoretical models showed the greater importance of the polymers around nanoparticles and the access resistance of nanopores to the current, when compared with translocation-based nanopore sensors. The signal magnitude was dominated by the change in access resistance of ∼4.25 Mω for all parameters, resulting in a robust system. The findings provide understandings of changes in current when nanopores are blocked, like in RNA trapping or nanopore blockade sensors, and are important for designing sensors based on nanopore blockades

An expedient strategy for the diversity-oriented synthesis of macrocyclic compounds with natural product-like characteristics

Naturally-derived macrocyclic compounds are associated with a diverse range of biological activities, including antibacterial effects, and there are over 100 marketed macrocycle drugs derived from natural products. However, synthetic macrocycles are widely considered to be poorly explored in antibiotic development (indeed, within drug discovery in general). This has been attributed to challenges associated with the generation of such compounds. Whilst there are synthetic methods that can produce large collections of structurally similar macrocycles (i.e., compounds with varying appendages based around similar core macrocyclic ring architectures) there is a relative dearth of strategies for the efficient generation of more structurally diverse macrocycle collections in which there is greater variation in the nature of macrocyclic scaffolds present. Such macrocycle collections should contain compounds with a broad range of biological activities (including antibacterial activities) and the requisite robust synthetic methodology useful for analogue synthesis and lead optimization once an active compound has been identified in a biological screen. Herein, we describe a new and expedient diversity-oriented synthesis (DOS) strategy for the generation of a library of novel structurally diverse macrocyclic compounds with a high level of scaffold diversity. The strategy is concise, proceeds from readily-available starting materials, is modular in nature and features a variety of macrocyclisation techniques. In this proof-of-concept study, the synthesis of several previously unreported macrocyclic compounds was achieved. Each of these macrocycles was based around a distinct molecular scaffold and contained natural product-like structural features (e.g., three-dimensionality and multiple hydrogen bond donors and acceptors) as well as synthetic handles for potential further elaboration. The successful generation of these macrocycles demonstrates the feasibility of the new DOS strategy as a synthetic platform for library generation.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council and Welcome Trust

Self-Propelled Initiative Collision at Microelectrodes with Vertically Mobile Micromotors

Impact experiments enable single particle analysis for many applications. However, the effect of the trajectory of a particle to an electrode on impact signals still requires further exploration. Here, we investigate the particle impact measurements versus motion using micromotors with controllable vertical motion. With biocatalytic cascade reactions, the micromotor system utilizes buoyancy as the driving force, thus enabling more regulated interactions with the electrode. With the aid of numerical simulations, the dynamic interactions between the electrode and micromotors are categorized into four representative patterns: approaching, departing, approaching-and-departing, and departing-and-reapproaching, which correspond well with the experimentally observed impact signals. This study offers a possibility of exploring the dynamic interactions between the electrode and particles, shedding light on the design of new electrochemical sensors