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Advanced healthcare materials: four considerations of protein detection by solid-state nanopore Electrical Technology

With the development of life science especially molecular biology biotechnology

has entered the era of "molecular diagnosis treatment". "Molecular diagnosis treatment" provides personalized medical services for human beings which can greatly improve the efficiency of disease diagnosis treatment. The core of realizing promoting "molecular diagnosis treatment" is to develop low-cost high sensitive high-throughput molecular detection technology. Solid state nanopore electrical technology based on current detection mode has attracted great interest in scientific research industry because it can detect single molecule in body fluid samples quickly sensitively.

solid-state nanopores refer to nanopores on solid material films prepared by a series of micro nano processing techniques. Its detection principle is similar to Coulter counter which is to identify characterize single molecule by detecting the current signal generated by a single molecule passing through a solid nanopore. Compared with natural membrane protein channels the mechanical thermal chemical properties of solid-state nanopores are more stable which can cover more extreme detection environment. In addition the pore size of solid-state nanopore can be flexibly adjusted which makes solid-state nanopore electrical technology can detect other molecules except single or double stred DNA str such as proteins nucleosomes viruses.

Professor Zhao Qing School of physics Peking University has been engaged in the research of solid-state nanopore electrical technology for the detection of single molecule for a long time. In a newly published review the key technical problems progress of solid-state nanopore electrical technology in protein quality inspection in recent years are summarized summarized. Based on the analysis of the current research status many years of experimental research in our laboratory four main problems (pore preparation sensitivity selectivity stability) on the road to clinical application of solid-state nanopore electrical technology are pointed out the solutions to these four problems in the current academic circles are also pointed out. The first problem of

is the preparation of pores. Rapid low-cost high-throughput preparation of solid-state nanopores is the core of clinical application of this technology. This paper reviews the evolution innovation of solid-state nanopore preparation methods from argon ion beam bombardment to focused electron beam etching finally to feedback controlled electrical breakdown which indicates that the preparation of solid-state nanopore is gradually evolving to high efficiency low cost. The second problem is the sensitivity of the hole. The sensitivity of solid-state nanopore electrical technology refers to the ability to distinguish different molecules or different configurations of a single molecule according to the current signal. This paper summarizes several key factors that affect the sensitivity such as the molecular through-hole time the thickness of solid-state nanopore the diameter of solid-state nanopore. The third problem is pore selectivity. Selectivity is the ability of solid-state nanopore to specifically recognize a protein in heterogeneous samples. This paper summarizes the potential of "surface modification method" "DNA probe method" in improving the selectivity of solid-state nanopore electrical technology. Finally we focus on the problem of the size expansion of solid-state nanopores in solution environment that is the stability point out that the stability is the key factor affecting the repeatability of the experiment. The related review papers were published in advanced healthcare materials Wiley journal. (DOI: 10.1002/adhm.202000933)

As a highly sensitive label free high-throughput single molecule detection technology

solid-state nanopore electrical technology has important application prospects in the field of in vitro diagnosis in the future. This review aims to summarize sort out the main problems innovative solutions in the current solid-state nanopore electrical technology lead readers to have a comprehensive profound understing of solid-state nanopore electrical technology so as to attract more attention In order to promote the development of this technology.

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