High Sensitivity Frequency Modulation Spectroscopy and the Path to Single Molecule Detection

2021 ◽  
Author(s):  
Gary C. Bjorklund ◽  
Edward A. Whittaker
Keyword(s):  
Single Molecule ◽  
Frequency Modulation ◽  
High Sensitivity ◽  
Single Molecule Detection ◽  
Modulation Spectroscopy

scholarly journals Nanopore Technology for the Application of Protein Detection

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1942
Author(s):  
Xiaoqing Zeng ◽  
Yang Xiang ◽  
Qianshan Liu ◽  
Liang Wang ◽  
Qianyun Ma ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Detection ◽  
High Sensitivity ◽  
Single Molecule Detection ◽  
Sequence Detection ◽  
Fast Detection ◽  
Material Basis ◽  
Sensing Technology ◽  
Detection Technology ◽  
Structure Recognition

Protein is an important component of all the cells and tissues of the human body and is the material basis of life. Its content, sequence, and spatial structure have a great impact on proteomics and human biology. It can reflect the important information of normal or pathophysiological processes and promote the development of new diagnoses and treatment methods. However, the current techniques of proteomics for protein analysis are limited by chemical modifications, large sample sizes, or cumbersome operations. Solving this problem requires overcoming huge challenges. Nanopore single molecule detection technology overcomes this shortcoming. As a new sensing technology, it has the advantages of no labeling, high sensitivity, fast detection speed, real-time monitoring, and simple operation. It is widely used in gene sequencing, detection of peptides and proteins, markers and microorganisms, and other biomolecules and metal ions. Therefore, based on the advantages of novel nanopore single-molecule detection technology, its application to protein sequence detection and structure recognition has also been proposed and developed. In this paper, the application of nanopore single-molecule detection technology in protein detection in recent years is reviewed, and its development prospect is investigated.

High-sensitivity frequency-modulation spectroscopy with a GaAlAs diode laser

1989 ◽  
Vol 6 (5) ◽  
pp. 871 ◽  
Author(s):  
Liang-Guo Wang ◽  
Duncan A. Tate ◽  
Haris Riris ◽  
Thomas F. Gallagher
Keyword(s):  
Diode Laser ◽  
Frequency Modulation ◽  
High Sensitivity ◽  
Modulation Spectroscopy

scholarly journals A microfluidic chip-compatible bioassay based on single-molecule detection with high sensitivity and multiplexing

Lab on a Chip ◽  
2010 ◽  
Vol 10 (7) ◽  
pp. 843 ◽  
Author(s):  
Randall E. Burton ◽  
Eric J. White ◽  
Ted R. Foss ◽  
Kevin M. Phillips ◽  
Robert H. Meltzer ◽  
...  
Keyword(s):  
Single Molecule ◽  
Microfluidic Chip ◽  
High Sensitivity ◽  
Single Molecule Detection

DNA Fragment Sizing by High-Sensitivity Flow Cytometry: Applications in Bacterial Identification

2005 ◽  
Author(s):  
Babetta L. Marrone ◽  
Robert C. Habbersett
Keyword(s):  
Flow Cytometry ◽  
Single Molecule ◽  
High Sensitivity ◽  
Flow Cytometer ◽  
Single Molecule Detection ◽  
Bacterial Identification ◽  
Probe Volume ◽  
Single Dna Molecules ◽  
Biological Particles ◽  
Dna Fragment

High-sensitivity, single-molecule detection in flow is a paradigm that has been defined at Los Alamos over the last two decades. A recent focus has been on applications of single- molecule detection for DNA fragment sizing using a compact, low-power, highsensitivity flow cytometer (HSFCM). There are three key aspects of our approach that distinguish it from conventional flow cytometry and yield the high level of sensitivity that we achieve: a detector with high photon-detection efficiency, a small probe volume to reduce background noise, and slow flow to provide extended analyte dwell time in the probe volume. An additional factor for applications in DNA fragment sizing is a DNA stain with significant fluorescence enhancement when bound to double-stranded DNA, and low background fluorescence in the unbound state. DNA fragment sizing by HSFCM has important applications in bacterial species and strain identification, where it can replace the cumbersome and time-consuming pulsed-field gel electrophoresis (PFGE) approach routinely used by public health labs for bacterial identification. The revolutionary capability to interrogate single DNA molecules, as well as potentially other submicron-sized biological particles, in a high-sensitivity flow cytometer will provide new scientific insights into cellular and molecular biology and introduce high-sensitivity flow cytometry to a wide variety of new applications in biotechnology. Flow cytometry has enabled major advances in the biomedical sciences by providing rapid, quantitative, and sensitive multiparameter measurements of individual cells and subcellular particles such as chromosomes. This analysis of individual entities produces information on population heterogeneity that is not revealed in ensemble measurements and that allows more precise quantitation of distinct attributes than is possi ble when measurements are done in bulk. However, one limitation of conventional flow cytometry is the inability to measure submicron-sized particles or weakly fluorescent particles labeled with fewer than several hundred fluorophores, primarily as a result of insufficient detection sensitivity. A wide variety of important biological particles, molecules, and molecular assemblies fall into these categories. There have been many reports of bacterial measurement and characterization by conventional flow cytometry, dating back to 1947. In 1979, Steen developed a microscope-based system specifically for applications in microbiology. Many bacteria are large enough to generate a light-scatter signal, which is useful for their detection.

scholarly journals A plasmonic “ac Wheatstone bridge” circuit for high-sensitivity phase measurement and single-molecule detection

2009 ◽  
Vol 106 (4) ◽  
pp. 043502 ◽  
Author(s):  
T. J. Davis ◽  
K. C. Vernon ◽  
D. E. Gómez
Keyword(s):  
Single Molecule ◽  
Bridge Circuit ◽  
Phase Measurement ◽  
High Sensitivity ◽  
Wheatstone Bridge ◽  
Single Molecule Detection

A Novel Tapered Optical Fiber-Based F0F1-ATPase Nanobiosensor

2014 ◽  
Vol 687-691 ◽  
pp. 3403-3406 ◽  
Author(s):  
Guan Jun Wang ◽  
Zhi Bin Wang
Keyword(s):  
Optical Fiber ◽  
Single Molecule ◽  
Molecular Motor ◽  
High Sensitivity ◽  
Fast Response ◽  
Experimental Results ◽  
Single Molecule Detection ◽  
Multimode Fiber ◽  
Tapered Optical Fiber ◽  
Detection Of Biomolecules

In this paper, a novel high sensitive nanobiosensor based on the combination of F0F1-ATPase molecular motor and Φ100nm tapered optical fiber is described, which as we known has never been reported before. Since the tapered optical fiber tip is well matched with the F0F1-ATPase complex in size, a superb sensitivity is theoretically expected. Experimental results show that this nanobiosensor’s sensitivity is about 3.5 times higher than the result of the experiment conducted on a F0F1-ATPase modified ordinary Φ50μm multimode fiber biosensor. The detecting time could be decreased correspondingly. Therefore a cheap, high sensitivity ,fast response, single molecule detection of biomolecules such as epidemic viruses would be achievable using this tapered optical fiber-based F0F1-ATPase nanobiosensor.

Direct Read and Quantify Damage Nucleotide from an Oligonucleotide Using a Single Molecule Interface

2019 ◽  
Author(s):  
Jiajun Wang ◽  
Meng-Yin Li ◽  
Jie Yang ◽  
Ya-Qian Wang ◽  
Xue-Yuan Wu ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Single Molecule ◽  
Genetic Diseases ◽  
High Sensitivity ◽  
Dna Lesions ◽  
Lesion Detection ◽  
The Novel ◽  
Structural Variations ◽  
Dna Lesion ◽  
Base Lesion

DNA lesion such as metholcytosine(<sup>m</sup>C), 8-OXO-guanine(<sup>O</sup>G), inosine(I) <i>etc</i> could cause the genetic diseases. Identification of the varieties of lesion bases are usually beyond the capability of conventional DNA sequencing which is mainly designed to discriminate four bases only. Therefore, lesion detection remain challenge due to the massive varieties and less distinguishable readouts for minor structural variations. Moreover, standard amplification and labelling hardly works in DNA lesions detection. Herein, we designed a single molecule interface from the mutant K238Q Aerolysin, whose confined sensing region shows the high compatible to capture and then directly convert each base lesion into distinguishable current readouts. Compared with previous single molecule sensing interface, the resolution of the K238Q Aerolysin nanopore is enhanced by 2-order. The novel K238Q could direct discriminate at least 3 types (<sup>m</sup>C, <sup>O</sup>G, I) lesions without lableing and quantify modification sites under mixed hetero-composition condition of oligonucleotide. Such nanopore could be further applied to diagnose genetic diseases at high sensitivity.

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