Applications of single-molecule detection in early disease diagnosis and enzymatic reaction study

Various single-molecule techniques were utilized for ultra-sensitive early diagnosis of viral DNA and antigen and basic mechanism study of enzymatic reactions. DNA of human papilloma virus (HPV) served as the screening target in a flow system. Alexa Fluor 532 (AF532) labeled single-stranded DNA probes were hybridized to the target HPV-16 DNA in solution. The individual hybridized molecules were imaged with an intensified charge-coupled device (ICCD) in two ways. In the single-color mode, target molecules were detected via fluorescence from hybridized probes only. This system could detect HPV-16 DNA in the presence of human genomic DNA down to 0.7 copy/cell and had a linear dynamic range of over 6 orders of magnitude. In the dual-color mode, fluorescence resonance energy transfer (FRET) was employed to achieve zero false-positive count. We also showed that DNA extracts from Pap test specimens did not interfere with the system. A surface-based method was used to improve the throughput of the flow system. HPV-16 DNA was hybridized to probes on a glass surface and detected with a total internal reflection fluorescence (TIRF) microscope. In the single-probe mode, the whole genome and target DNA were fluorescently labeled before hybridization, and the detection limit is similar to the flow system. In the dual-probe mode, a second probe was introduced. The linear dynamic range covers 1.44-7000 copies/cell, which is typical of early infection to near-cancer stages. The dual-probe method was tested with a crudely prepared sample. Even with reduced hybridization efficiency caused by the interference of cellular materials, we were still able to differentiate infected cells from healthy cells. Detection and quantification of viral antigen with a novel single-molecule immunosorbent assay (SMISA) was achieved. Antigen from human immunodeficiency virus type 1(HIV-1) was chosen to be the target in this study. The target was sandwiched between a monoclonal capture antibody and a polyclonal detector antibody. The capture antibody was covalently immobilized on modified glass slides. The detector antibody was conjugated with AF532 labeled secondary antibody prior to being used as probe for the antigen. Imaging was performed with a TIRF system. This technique is demonstrated for detecting HIV-1 p24 antigen down to 0.1 pg/mL with a dynamic range of over 4 orders of magnitude. A Langmuir isotherm fit the molecule count dependence on the target concentration. The results also showed that neither sensitivity nor dynamic range was affected by the biological matrix. SMISA is therefore a promising approach for the early diagnosis of virus-induced diseases. Single-molecule enzymatic kinetics and enantioselectivity were monitored in real time by using TIRF microscopy. AF532 labeled poly-L-lysine (PLL) or poly-D-lysine (PDL) was covalently immobilized on a dithiobis (succinimidyl undecanoate) self-assembled monolayer (DSU SAM). Chain shortening due to enzymatic hydrolysis resulted in the reduction of the individual fluorescence intensities. A broad distribution was obtained when 100 single-molecule half-lives were analyzed. However, the detailed hydrolysis process involved also a long-lived component and an induction period that varied significantly among molecules. Charge and steric heterogeneity at the surface are responsible for these features

Verification of arbitrary entangled states with homogeneous local measurements

Quantum state verification (QSV) is the task of using local measurements only to verify that a given quantum device does produce the desired target state. Up to now, certain types of entangled states can be verified efficiently or even optimally by QSV. However, given an arbitrary entangled state, how to design its verification protocol remains an open problem. In this work, we present a systematic strategy to tackle this problem by considering the locality of what we initiate as the choice-independent measurement protocols, whose operators can be directly achieved when they are homogeneous. Taking several typical entangled states as examples, we demonstrate the explicit procedures of the protocol design using standard Pauli projections. Moreover, our framework can be naturally extended to other tasks such as the construction of entanglement witness, and even parameter estimation.Comment: 6+7 pages, 1 figure; Comments are welcome

Deterministic realization of collective measurements via photonic quantum walks

Collective measurements on identically prepared quantum systems can extract more information than local measurements, thereby enhancing information-processing efficiency. Although this nonclassical phenomenon has been known for two decades, it has remained a challenging task to demonstrate the advantage of collective measurements in experiments. Here we introduce a general recipe for performing deterministic collective measurements on two identically prepared qubits based on quantum walks. Using photonic quantum walks, we realize experimentally an optimized collective measurement with fidelity 0.9946 without post selection. As an application, we achieve the highest tomographic efficiency in qubit state tomography to date. Our work offers an effective recipe for beating the precision limit of local measurements in quantum state tomography and metrology. In addition, our study opens an avenue for harvesting the power of collective measurements in quantum information processing and for exploring the intriguing physics behind this power.Comment: Close to the published versio

Aligning Linguistic Words and Visual Semantic Units for Image Captioning

Image captioning attempts to generate a sentence composed of several linguistic words, which are used to describe objects, attributes, and interactions in an image, denoted as visual semantic units in this paper. Based on this view, we propose to explicitly model the object interactions in semantics and geometry based on Graph Convolutional Networks (GCNs), and fully exploit the alignment between linguistic words and visual semantic units for image captioning. Particularly, we construct a semantic graph and a geometry graph, where each node corresponds to a visual semantic unit, i.e., an object, an attribute, or a semantic (geometrical) interaction between two objects. Accordingly, the semantic (geometrical) context-aware embeddings for each unit are obtained through the corresponding GCN learning processers. At each time step, a context gated attention module takes as inputs the embeddings of the visual semantic units and hierarchically align the current word with these units by first deciding which type of visual semantic unit (object, attribute, or interaction) the current word is about, and then finding the most correlated visual semantic units under this type. Extensive experiments are conducted on the challenging MS-COCO image captioning dataset, and superior results are reported when comparing to state-of-the-art approaches.Comment: 8 pages, 5 figures. Accepted by ACM MM 201

Revealing the pulse-induced electroplasticity by decoupling electron wind force

Micro/nano electromechanical systems and nanodevices often suffer from degradation under electrical pulse. However, the origin of pulse-induced degradation remains an open question. Herein, we investigate the defect dynamics in Au nanocrystals under pulse conditions. By decoupling the electron wind force via a properly-designed in situ TEM electropulsing experiment, we reveal a non-directional migration of Σ3{112} incoherent twin boundary upon electropulsing, in contrast to the expected directional migration under electron wind force. Quantitative analyses demonstrate that such exceptional incoherent twin boundary migration is governed by the electron-dislocation interaction that enhances the atom vibration at dislocation cores, rather than driven by the electron wind force in classic model. Our observations provide valuable insights into the origin of electroplasticity in metallic materials at the atomic level, which are of scientific and technological significances to understanding the electromigration and resultant electrical damage/failure inmicro/ nano-electronic devices