scholarly journals Single-Molecule Counting of Nucleotide by Electrophoresis with Nanochannel-Integrated Nano-Gap Devices

Micromachines ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 982
Author(s):  
Takahito Ohshiro ◽  
Yuki Komoto ◽  
Masateru Taniguchi
Keyword(s):  
Single Molecule ◽  
High Performance ◽  
Electrical Measurement ◽  
Identification Accuracy ◽  
Detection And Identification ◽  
Long Duration ◽  
Order Of Magnitude ◽  
Tris Borate Edta ◽  
Optimized Conditions ◽  
Electro Osmotic Flow

We utilized electrophoresis to control the fluidity of sample biomolecules in sample aqueous solutions inside the nanochannel for single-molecule detection by using a nanochannel-integrated nanogap electrode, which is composed of a nano-gap sensing electrode, nanochannel, and tapered focusing channel. In order to suppress electro-osmotic flow and thermal convection inside this nanochannel, we optimized the reduction ratios of the tapered focusing channel, and the ratio of inlet 10 μm to outlet 0.5 μm was found to be high performance of electrophoresis with lower concentration of 0.05 × TBE (Tris/Borate/EDTA) buffer containing a surfactant of 0.1 w/v% polyvinylpyrrolidone (PVP). Under the optimized conditions, single-molecule electrical measurement of deoxyguanosine monophosphate (dGMP) was performed and it was found that the throughput was significantly improved by nearly an order of magnitude compared to that without electrophoresis. In addition, it was also found that the long-duration signals that could interfere with discrimination were significantly reduced. This is because the strong electrophoresis flow inside the nanochannels prevents the molecules’ adsorption near the electrodes. This single-molecule electrical measurement with nanochannel-integrated nano-gap electrodes by electrophoresis significantly improved the throughput of signal detection and identification accuracy.

Substituent-mediated quantum interference toward a giant single-molecule conductance variation

2021 ◽  
Author(s):  
Yi-Fan Zhou ◽  
Wen-Yan Chang ◽  
Jing-Zhe Chen ◽  
Jun-Ren Huang ◽  
Jia-Ying Fu ◽  
...  
Keyword(s):  
Single Molecule ◽  
Quantum Interference ◽  
High Performance ◽  
Substituent Effects ◽  
Molecular Junctions ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Transmission Coefficients ◽  
Order Of Magnitude ◽  
Promising Perspective

Abstract Quantum interference (QI) in single molecular junctions shows a promising perspective for realizing conceptual nanoelectronics. However, controlling and modulating the QI remains a big challenge. Herein, two-type substituents at different positions of meta-linked benzene, namely electron-donating methoxy (-OMe) and electron-withdrawing nitryl (-NO2), are designed and synthesized to investigate the substituent effects on QI. The calculated transmission coefficients T(E) indicates that -OMe and -NO2 could remove the antiresonance and destructive quantum interference (DQI)-induced transmission dips at position 2. -OMe could raise the antiresonance energy at position 4 while -NO2 groups removes the DQI features. For substituents at position 5, both of them are nonactive for tuning QI. The conductance measurements by scanning tunneling microscopy break junction (STM-BJ) show a good agreement with the theoretical prediction. More than two order of magnitude single-molecule conductance on/off ratio could be achieved at the different positions of -NO2 substituent groups at room temperature. The present work proves chemical substituents can be used for tuning QI features in single molecular junctions, which provides a feasible way toward realization of high-performance molecular devices.

scholarly journals A machine learning approach for accurate and real-time DNA sequence identification

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yiren Wang ◽  
Mashari Alangari ◽  
Joshua Hihath ◽  
Arindam K. Das ◽  
M. P. Anantram
Keyword(s):  
Real Time ◽  
Dna Sequence ◽  
Single Molecule ◽  
Identification Accuracy ◽  
Measuring System ◽  
Identification System ◽  
Genetic Sequencing ◽  
Sequence Identification ◽  
Tree Classifier ◽  
Single Mismatch

Abstract Background The all-electronic Single Molecule Break Junction (SMBJ) method is an emerging alternative to traditional polymerase chain reaction (PCR) techniques for genetic sequencing and identification. Existing work indicates that the current spectra recorded from SMBJ experimentations contain unique signatures to identify known sequences from a dataset. However, the spectra are typically extremely noisy due to the stochastic and complex interactions between the substrate, sample, environment, and the measuring system, necessitating hundreds or thousands of experimentations to obtain reliable and accurate results. Results This article presents a DNA sequence identification system based on the current spectra of ten short strand sequences, including a pair that differs by a single mismatch. By employing a gradient boosted tree classifier model trained on conductance histograms, we demonstrate that extremely high accuracy, ranging from approximately 96 % for molecules differing by a single mismatch to 99.5 % otherwise, is possible. Further, such accuracy metrics are achievable in near real-time with just twenty or thirty SMBJ measurements instead of hundreds or thousands. We also demonstrate that a tandem classifier architecture, where the first stage is a multiclass classifier and the second stage is a binary classifier, can be employed to boost the single mismatched pair’s identification accuracy to 99.5 %. Conclusions A monolithic classifier, or more generally, a multistage classifier with model specific parameters that depend on experimental current spectra can be used to successfully identify DNA strands.

scholarly journals Tomato Leaf Disease Diagnosis Based on Improved Convolution Neural Network by Attention Module

Agriculture ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 651
Author(s):  
Shengyi Zhao ◽  
Yun Peng ◽  
Jizhan Liu ◽  
Shuo Wu
Keyword(s):  
Neural Network ◽  
High Performance ◽  
Model Comparison ◽  
Research Direction ◽  
Disease Diagnosis ◽  
Tomato Leaf ◽  
Identification Accuracy ◽  
Main Research ◽  
Proposed Model ◽  
Complex Features

Crop disease diagnosis is of great significance to crop yield and agricultural production. Deep learning methods have become the main research direction to solve the diagnosis of crop diseases. This paper proposed a deep convolutional neural network that integrates an attention mechanism, which can better adapt to the diagnosis of a variety of tomato leaf diseases. The network structure mainly includes residual blocks and attention extraction modules. The model can accurately extract complex features of various diseases. Extensive comparative experiment results show that the proposed model achieves the average identification accuracy of 96.81% on the tomato leaf diseases dataset. It proves that the model has significant advantages in terms of network complexity and real-time performance compared with other models. Moreover, through the model comparison experiment on the grape leaf diseases public dataset, the proposed model also achieves better results, and the average identification accuracy of 99.24%. It is certified that add the attention module can more accurately extract the complex features of a variety of diseases and has fewer parameters. The proposed model provides a high-performance solution for crop diagnosis under the real agricultural environment.

scholarly journals N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dandan Shan ◽  
Joseph M. Johnson ◽  
Syrena C. Fernandes ◽  
Hannah Suib ◽  
Soyoon Hwang ◽  
...  
Keyword(s):  
Single Molecule ◽  
High Performance ◽  
Point Of Care ◽  
Capillary Blood ◽  
Molecular Testing ◽  
Sample Collection ◽  
Protein Assay ◽  
N Protein ◽  
Protein Levels ◽  
Percent Agreement

AbstractThe COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1–7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.

scholarly journals A Peristaltic Micropump Based on the Fast Electrochemical Actuator: Design, Fabrication, and Preliminary Testing

Actuators ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 62
Author(s):  
Ilia Uvarov ◽  
Pavel Shlepakov ◽  
Artem Melenev ◽  
Kechun Ma ◽  
Vitaly Svetovoy ◽  
...  
Keyword(s):  
High Performance ◽  
Drug Delivery Systems ◽  
Main Part ◽  
Fabrication Technology ◽  
Fabrication Procedure ◽  
Order Of Magnitude ◽  
Peristaltic Micropump ◽  
Biomedical Field ◽  
Lift Off ◽  
Actuator Design

Microfluidic devices providing an accurate delivery of fluids at required rates are of considerable interest, especially for the biomedical field. The progress is limited by the lack of micropumps, which are compact, have high performance, and are compatible with standard microfabrication. This paper describes a micropump based on a new driving principle. The pump contains three membrane actuators operating peristaltically. The actuators are driven by nanobubbles of hydrogen and oxygen, which are generated in the chamber by a series of short voltage pulses of alternating polarity applied to the electrodes. This process guaranties the response time of the actuators to be much shorter than that of any other electrochemical device. The main part of the pump has a size of about 3 mm, which is an order of magnitude smaller in comparison with conventional micropumps. The pump is fabricated in glass and silicon wafers using standard cleanroom processes. The channels are formed in SU-8 photoresist and the membrane is made of SiNx. The channels are sealed by two processes of bonding between SU-8 and SiNx. Functionality of the channels and membranes is demonstrated. A defect of electrodes related to the lift-off fabrication procedure did not allow a demonstration of the pumping process although a flow rate of 1.5 µl/min and dosage accuracy of 0.25 nl are expected. The working characteristics of the pump make it attractive for the use in portable drug delivery systems, but the fabrication technology must be improved.

scholarly journals Highly efficient self-powered perovskite photodiode with an electron-blocking hole-transport NiOx layer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amir Muhammad Afzal ◽  
In-Gon Bae ◽  
Yushika Aggarwal ◽  
Jaewoo Park ◽  
Hye-Ryeon Jeong ◽  
...  
Keyword(s):  
Energy Harvesting ◽  
Bias Voltage ◽  
High Performance ◽  
Hole Transport ◽  
Transport Layer ◽  
Hole Transport Layer ◽  
Zero Bias ◽  
Decay Times ◽  
Order Of Magnitude ◽  
Self Powered

AbstractHybrid organic–inorganic perovskite materials provide noteworthy compact systems that could offer ground-breaking architectures for dynamic operations and advanced engineering in high-performance energy-harvesting optoelectronic devices. Here, we demonstrate a highly effective self-powered perovskite-based photodiode with an electron-blocking hole-transport layer (NiOx). A high value of responsivity (R = 360 mA W−1) with good detectivity (D = 2.1 × 1011 Jones) and external quantum efficiency (EQE = 76.5%) is achieved due to the excellent interface quality and suppression of the dark current at zero bias voltage owing to the NiOx layer, providing outcomes one order of magnitude higher than values currently in the literature. Meanwhile, the value of R is progressively increased to 428 mA W−1 with D = 3.6 × 1011 Jones and EQE = 77% at a bias voltage of − 1.0 V. With a diode model, we also attained a high value of the built-in potential with the NiOx layer, which is a direct signature of the improvement of the charge-selecting characteristics of the NiOx layer. We also observed fast rise and decay times of approximately 0.9 and 1.8 ms, respectively, at zero bias voltage. Hence, these astonishing results based on the perovskite active layer together with the charge-selective NiOx layer provide a platform on which to realise high-performance self-powered photodiode as well as energy-harvesting devices in the field of optoelectronics.

scholarly journals Biosensing with optical fiber gratings

Nanophotonics ◽  
2017 ◽  
Vol 6 (4) ◽  
pp. 663-679 ◽  
Author(s):  
Francesco Chiavaioli ◽  
Francesco Baldini ◽  
Sara Tombelli ◽  
Cosimo Trono ◽  
Ambra Giannetti
Keyword(s):  
Optical Fiber ◽  
Single Molecule ◽  
High Performance ◽  
Performance Metrics ◽  
Surrounding Medium ◽  
Remote Measurement ◽  
Fiber Gratings ◽  
Practical Applications ◽  
Technology Platforms ◽  
Optical Fiber Gratings

AbstractOptical fiber gratings (OFGs), especially long-period gratings (LPGs) and etched or tilted fiber Bragg gratings (FBGs), are playing an increasing role in the chemical and biochemical sensing based on the measurement of a surface refractive index (RI) change through a label-free configuration. In these devices, the electric field evanescent wave at the fiber/surrounding medium interface changes its optical properties (i.e. intensity and wavelength) as a result of the RI variation due to the interaction between a biological recognition layer deposited over the fiber and the analyte under investigation. The use of OFG-based technology platforms takes the advantages of optical fiber peculiarities, which are hardly offered by the other sensing systems, such as compactness, lightness, high compatibility with optoelectronic devices (both sources and detectors), and multiplexing and remote measurement capability as the signal is spectrally modulated. During the last decade, the growing request in practical applications pushed the technology behind the OFG-based sensors over its limits by means of the deposition of thin film overlays, nanocoatings, and nanostructures, in general. Here, we review efforts toward utilizing these nanomaterials as coatings for high-performance and low-detection limit devices. Moreover, we review the recent development in OFG-based biosensing and identify some of the key challenges for practical applications. While high-performance metrics are starting to be achieved experimentally, there are still open questions pertaining to an effective and reliable detection of small molecules, possibly up to single molecule, sensing in vivo and multi-target detection using OFG-based technology platforms.

scholarly journals Nearfield trapping increases lifetime of single-molecule junction by one order of magnitude

2020 ◽  
Author(s):  
Albert C. Aragonès ◽  
Katrin F. Domke
Keyword(s):  
Molecular Electronics ◽  
Single Molecule ◽  
Fold Increase ◽  
Trapping Efficiency ◽  
Non Invasive ◽  
Order Of Magnitude ◽  
Molecule Junction ◽  
Single Molecule Junction ◽  
The Difference ◽  
Power Densities

Abstract Progress in molecular electronics (ME) is largely based on improved understanding of the properties of single molecules (SM) trapped for seconds or longer to enable their detailed characterization. We present a plasmon-supported break-junction (PBJ) platform to significantly increase the lifetime of SM junctions of 1,4-benzendithiol (BDT) without the need for chemical modification of molecule or electrode. Moderate far-field power densities of ca. 11 mW/µm2 lead to a >10-fold increase in minimum lifetime compared to laser-OFF conditions. The nearfield trapping efficiency is twice as large for bridge-site contact compared to hollow-site geometry, which can be attributed to the difference in polarizability. Current measurements and tip-enhanced Raman spectra confirm that native structure and contact geometry of BDT are preserved during the PBJ experiment. By providing a non-invasive pathway to increase short lifetimes of SM junctions, PBJ is a valuable approach for ME, paving the way for improved SM sensing and recognition platforms.

scholarly journals Workstation benchmark of Spark Capable Genome Analysis ToolKit 4 Variant Calling

2020 ◽  
Author(s):  
Marcus H. Hansen ◽  
Anita T. Simonsen ◽  
Hans B. Ommen ◽  
Charlotte G. Nyvold
Keyword(s):  
Dna Sequencing ◽  
Genome Analysis ◽  
High Speed ◽  
High Performance ◽  
Variant Calling ◽  
Amplicon Sequencing ◽  
Targeted Sequencing ◽  
Sequencing Analysis ◽  
Genome Analysis Toolkit ◽  
Order Of Magnitude

AbstractBackgroundRapid and practical DNA-sequencing processing has become essential for modern biomedical laboratories, especially in the field of cancer, pathology and genetics. While sequencing turn-over time has been, and still is, a bottleneck in research and diagnostics, the field of bioinformatics is moving at a rapid pace – both in terms of hardware and software development. Here, we benchmarked the local performance of three of the most important Spark-enabled Genome analysis toolkit 4 (GATK4) tools in a targeted sequencing workflow: Duplicate marking, base quality score recalibration (BQSR) and variant calling on targeted DNA sequencing using a modest hyperthreading 12-core single CPU and a high-speed PCI express solid-state drive.ResultsCompared to the previous GATK version the performance of Spark-enabled BQSR and HaplotypeCaller is shifted towards a more efficient usage of the available cores on CPU and outperforms the earlier GATK3.8 version with an order of magnitude reduction in processing time to analysis ready variants, whereas MarkDuplicateSpark was found to be thrice as fast. Furthermore, HaploTypeCallerSpark and BQSRPipelineSpark were significantly faster than the equivalent GATK4 standard tools with a combined ∼86% reduction in execution time, reaching a median rate of ten million processed bases per second, and duplicate marking was reduced ∼42%. The called variants were found to be in close agreement between the Spark and non-Spark versions, with an overall concordance of 98%. In this setup, the tools were also highly efficient when compared execution on a small 72 virtual CPU/18-node Google Cloud cluster.ConclusionIn conclusion, GATK4 offers practical parallelization possibilities for DNA sequence processing, and the Spark-enabled tools optimize performance and utilization of local CPUs. Spark utilizing GATK variant calling is several times faster than previous GATK3.8 multithreading with the same multi-core, single CPU, configuration. The improved opportunities for parallel computations not only hold implications for high-performance cluster, but also for modest laboratory or research workstations for targeted sequencing analysis, such as exome, panel or amplicon sequencing.

scholarly journals A simple surface modification to generate atomically-flat and hydrophobic substrates for gliding assays with protein motors

2021 ◽  
Author(s):  
Isadonna Tengganu ◽  
Neil Karerakattil ◽  
Swarup Dey ◽  
Devika Kishnan ◽  
Rizal Hariadi
Keyword(s):  
Single Molecule ◽  
Vapor Deposition ◽  
Glass Capillary ◽  
High Background ◽  
Protein Motors ◽  
Order Of Magnitude ◽  
Protein Motor ◽  
Glass Surfaces ◽  
Atomically Flat

In vitro gliding assay is a well-established assay for determining the activity of protein motors, such as actin-associated myosins and microtubule-associated kinesins and dyneins. In one of the conventional methods, protein motors are immobilized onto a nitrocellulose-coated coverslip and it propels actin filaments in the presence of ATP. Gliding assays also serve as the foundation for protein-motor-based nanotechnological devices such as biosensing and sorting. However, the preparation of nitrocellulose-coated coverslips is time-consuming and produces rough surfaces. Furthermore, the nitrocellulose film exhibits high background autofluorescence, which can be a problem in single-molecule measurements. Here, we investigated the use of hexamethyldisilazane (HMDS) to study actomyosin function and characterized its physical properties on glass coverslips and glass capillary tubes. We showed that the total preparation time to coat a coverslip with HMDS is <30 minutes, which is 1 order of magnitude faster than the >12-hour protocol for coating glass surfaces with nitrocellulose. In contrast to nitrocellulose film, HMDS vapor deposition is effortless and provides an atomically flat surface with low autofluorescence. In addition, HMDS does not interfere with myosin function, which is indicated by the similar actin gliding speed when compared with nitrocellulose. Our results show that HMDS vapor deposition is a more favorable surface treatment to nitrocellulose for in vitro gliding assay.

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