scholarly journals Application of Solid-State Nanopore in Protein Detection

2020 ◽  
Vol 21 (8) ◽  
pp. 2808 ◽  
Author(s):  
Yuhan Luo ◽  
Linlin Wu ◽  
Jing Tu ◽  
Zuhong Lu

A protein is a kind of major biomacromolecule of life. Its sequence, structure, and content in organisms contains quite important information for normal or pathological physiological process. However, research of proteomics is facing certain obstacles. Only a few technologies are available for protein analysis, and their application is limited by chemical modification or the need for a large amount of sample. Solid-state nanopore overcomes some shortcomings of the existing technology, and has the ability to detect proteins at a single-molecule level, with its high sensitivity and robustness of device. Many works on detection of protein molecules and discriminating structure have been carried out in recent years. Single-molecule protein sequencing techniques based on solid-state nanopore are also been proposed and developed. Here, we categorize and describe these efforts and progress, as well as discuss their advantages and drawbacks.

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongcheng Yang ◽  
Muhammad Saqib ◽  
Rui Hao

Nanopore-based single-entity detection shows immense potential in sensing and sequencing technologies. Solid-state nanopores permit unprecedented detail while preserving mechanical robustness, reusability, adjustable pore size, and stability in different physical and chemical environments. The transmission electron microscope (TEM) has evolved into a powerful tool for fabricating and characterizing nanometer-sized pores within a solid-state ultrathin membrane. By detecting differences in the ionic current signals due to single-entity translocation through the nanopore, solid-state nanopores can enable gene sequencing and single molecule/nanoparticle detection with high sensitivity, improved acquisition speed, and low cost. Here we briefly discuss the recent progress in the modification and characterization of TEM-fabricated nanopores. Moreover, we highlight some key applications of these nanopores in nucleic acids, protein, and nanoparticle detection. Additionally, we discuss the future of computer simulations in DNA and protein sequencing strategies. We also attempt to identify the challenges and discuss the future development of nanopore-detection technology aiming to promote the next-generation sequencing technology.


Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1942
Author(s):  
Xiaoqing Zeng ◽  
Yang Xiang ◽  
Qianshan Liu ◽  
Liang Wang ◽  
Qianyun Ma ◽  
...  

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.


2021 ◽  
Author(s):  
Chic-Ping Mao ◽  
Shih-Chin Wang ◽  
Yu-Pin Su ◽  
Ssu-Hsueh Tseng ◽  
Liangmei He ◽  
...  

The ability to identify and characterize individual biomarker protein molecules in patient blood samples could enable diagnosis of diseases at an earlier stage, when treatment is typically more effective. Single-molecule imaging offers a promising approach to accomplish this goal. However, thus far single-molecule imaging methods have only been used to monitor protein molecules in solutions or cell lysates, and have not been translated into the clinical arena. Furthermore, the detection limit of these methods has been confined to the picomolar (10-12 M) range. In many diseases, the circulating concentrations of biomarker proteins fall several orders of magnitude below this range. Here we describe Single-Molecule Augmented Capture (SMAC), a single-molecule imaging technique to visualize, quantify, and characterize individual protein molecules of interest down to the subfemtomolar (<10-15 M) range, even in complex biologic fluids. We demonstrate SMAC in a wide variety of applications with human blood samples, including the analysis of disease-associated secreted proteins, membrane proteins, and rare intracellular proteins. Using ovarian cancer as a model, a lethal malignancy in which high-grade disease is driven almost universally by alterations in the TP53 gene and frequently only diagnosed at a late, incurable stage, we found that mutant pattern p53 proteins are released into the blood in patients at an early stage in disease progression. SMAC opens the door to the application of single-molecule imaging in non-invasive disease profiling and allows for the analysis of circulating mutant proteins as a new class of highly specific disease biomarkers. The SMAC platform can be adapted to multiplex or high-throughput formats to characterize heterogeneous biochemical and structural features of circulating proteins-of-interest.


2020 ◽  
Vol 1 (8) ◽  
pp. 2908-2916 ◽  
Author(s):  
Rameshwar L. Kumawat ◽  
Biswarup Pathak

The TOC features a scheme of solid-state nanochannel-based DNA sequencing techniques. DNA nucleobases can be analyzed at the single-molecule level by adsorption on topologically extended line defects in the graphene-based electrode setup.


2020 ◽  
Vol 165 ◽  
pp. 112289 ◽  
Author(s):  
Youwen Zhang ◽  
Xiaohan Chen ◽  
Ceming Wang ◽  
Golbarg M. Roozbahani ◽  
Hsueh-Chia Chang ◽  
...  

2017 ◽  
Vol 53 (2) ◽  
pp. 436-439 ◽  
Author(s):  
Jinglin Kong ◽  
Jinbo Zhu ◽  
Ulrich F. Keyser

A novel nanopore-DNA carrier method is demonstrated for SNP detection and following DNA strand displacement kinetics at the single molecule level.


2017 ◽  
Vol 46 (13) ◽  
pp. 3962-3979 ◽  
Author(s):  
Jian-Feng Li ◽  
Chao-Yu Li ◽  
Ricardo F. Aroca

Fluorescence spectroscopy with strong emitters is a remarkable tool with ultra-high sensitivity for detection and imaging down to the single-molecule level.


Sensors ◽  
2019 ◽  
Vol 19 (24) ◽  
pp. 5403 ◽  
Author(s):  
Adi Hendler-Neumark ◽  
Gili Bisker

Nanosensors have a central role in recent approaches to molecular recognition in applications like imaging, drug delivery systems, and phototherapy. Fluorescent nanoparticles are particularly attractive for such tasks owing to their emission signal that can serve as optical reporter for location or environmental properties. Single-walled carbon nanotubes (SWCNTs) fluoresce in the near-infrared part of the spectrum, where biological samples are relatively transparent, and they do not photobleach or blink. These unique optical properties and their biocompatibility make SWCNTs attractive for a variety of biomedical applications. Here, we review recent advancements in protein recognition using SWCNTs functionalized with either natural recognition moieties or synthetic heteropolymers. We emphasize the benefits of the versatile applicability of the SWCNT sensors in different systems ranging from single-molecule level to in-vivo sensing in whole animal models. Finally, we discuss challenges, opportunities, and future perspectives.


2021 ◽  
Vol 7 (33) ◽  
pp. eabg6522
Author(s):  
Chih-Ping Mao ◽  
Shih-Chin Wang ◽  
Yu-Pin Su ◽  
Ssu-Hsueh Tseng ◽  
Liangmei He ◽  
...  

The ability to characterize individual biomarker protein molecules in patient blood samples could enable diagnosis of diseases at an earlier stage, when treatment is typically more effective. Single-molecule imaging offers a promising approach to accomplish this goal. However, thus far, single-molecule imaging methods have not been translated into the clinical setting. The detection limit of these methods has been confined to the picomolar (10−12 M) range, several orders of magnitude higher than the circulating concentrations of biomarker proteins present in many diseases. Here, we describe single-molecule augmented capture (SMAC), a single-molecule imaging technique to quantify and characterize individual protein molecules of interest down to the subfemtomolar (<10−15 M) range. We demonstrate SMAC in a variety of applications with human blood samples, including the analysis of disease-associated secreted proteins, membrane proteins, and rare intracellular proteins. SMAC opens the door to the application of single-molecule imaging in noninvasive disease profiling.


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