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2023 , Vol. 81 >Issue 7: 857 - 868

DOI: https://doi.org/10.6023/A23040149

综述

受限纳尺度下蛋白质输运的主动操纵技术

  • 马超凡 ,
  • 徐伟 ,
  • 刘巍 ,
  • 徐昌晖 ,
  • 沙菁?
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  • a 东南大学机械工程学院 南京 211189
    b 东南大学 江苏省微纳生物医学仪器设计与制造重点实验室 南京 211189

马超凡, 男, 东南大学机械工程学院博士研究生. 主要从事生物纳米孔蛋白质检测与构象分析的研究.

沙菁㛃, 女, 东南大学机械工程学院设计工程系, 教授, 博士生导师. 主要研究方向为微纳流体系统、微纳传感器设计. 先后主持或完成包括4项国家自然科学基金(其中一项优秀结题)、参与1项973计划、1项国家自然科学基金重点项目. 近几年, 在JACS、ACS Nano、Small、Nanoscale、Analytical Chemistry、ACS Sensors、Nanotechnology、Appl. Phys. Lett.等微纳领域权威国际期刊发表SCI论文50余篇(含JCR一区、二区论文近50篇, 影响因子超10.0论文6篇). 申请发明专利18项, 已经获得授权13项. 中国机械工程学会高级会员、ASME会员、长期担任《Lab on a Chip》、《Nanotechnology》、《BIOTECHNOLOGY AND BIOENGINEERING》、《中国科学》等期刊的审稿人.

收稿日期: 2023-04-20

  网络出版日期: 2023-06-01

基金资助

国家自然科学基金(52075099); 国家自然科学基金(52035003)

收起

Proactive Manipulation Techniques for Protein Transport at Confined Nanoscale

  • Chaofan Ma ,
  • Wei Xu ,
  • Wei Liu ,
  • Changhui Xu ,
  • Jingjie Sha
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  • a School of Mechanical Engineering, Southeast University, Nanjing 211189
    b Jiangsu Key Laboratory for Design and Manufacture of Micro-nano Biomedical Instruments, Southeast University,Nanjing 211189
*E-mail:

Received date: 2023-04-20

  Online published: 2023-06-01

Supported by

National Natural Science Foundation of China(52075099); National Natural Science Foundation of China(52035003)

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摘要

蛋白质是人体细胞、组织的重要组成部分, 与众多代谢活动密切相关, 它们的一些微小改变就可能引发人体的重大疾病. 因此, 蛋白质检测是生物化学领域的重要课题. 纳米孔技术能够在单分子水平甚至单氨基酸水平上实时检测蛋白质, 有望成为最低成本和最高效的蛋白质检测方法之一. 然而, 使用纳米孔检测蛋白质时, 由于实验条件和检测策略的原因, 使得蛋白质在纳米孔中驻留时间过短, 无法从蛋白质捕获的电信号中清晰地反映更多的生物细节信息. 解决这一问题的关键在于控制蛋白质通过纳米孔时的输运速度, 满足传感器件带宽的要求. 本综述从外部力场竞争、内部力场相互作用、亲疏水相互作用、空间位阻效应等角度综述了蛋白质在纳米孔中输运的主动操纵技术, 目的是提高纳米孔对蛋白质的捕获频率, 延长蛋白质在纳米孔内的驻留时间, 以实现高分辨率的蛋白质检测, 充分揭示蛋白质分子的构象变化机制、反应动力学, 甚至实现蛋白质测序等. 最后对纳米孔传感技术在蛋白质检测方面存在的巨大挑战和发展趋势进行了详细展望和总结阐述.

关键词： 蛋白质检测; 纳米孔; 操纵方法; 捕获时间; 纳尺度输运

本文引用格式

马超凡 , 徐伟 , 刘巍 , 徐昌晖 , 沙菁? . 受限纳尺度下蛋白质输运的主动操纵技术[J]. 化学学报, 2023 , 81(7) : 857 -868 . DOI: 10.6023/A23040149

Abstract

Proteins are important components of human cells and tissues and are closely related to numerous metabolic activities, and some small changes in them may trigger major diseases in the human body. Therefore, protein detection is an important topic in the field of biochemistry. Nanopore technology is capable of real-time protein detection at the single molecule level or even at the single amino acid level, and is expected to be one of the lowest costs and most efficient protein detection methods. However, when using nanopores to detect proteins, the experimental conditions and detection strategy make the protein residence time in the nanopore too short to clearly reflect more detailed biological information from the electrical signal captured by the protein. The critical solution to this problem lies in controlling the transport rate of proteins through the nanopore to meet the bandwidth of the sensor device. In this paper, the active manipulation techniques of protein transport in nanopores are reviewed from the perspectives of external force field competition, internal force field interaction, hydrophilic interaction, and spatial resistance effect, with the aim of improving the capture frequency of proteins by nanopores and prolonging the residence time of proteins in nanopores to achieve high-resolution protein detection, fully reveal the conformational change mechanism of protein molecules, reaction kinetics, and even realize protein sequencing, etc. Finally, the great challenges and development trends of nanopore sensing technology for protein detection are described in detail.

Key words： protein detection; nanopore; manipulation method; residence time; nanoscale transport

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