Fabrication And Sensing Applications Of Glass Nanopore

Transmembrane mass transportation via transmembrane channels or ion channels on the cell membrane of organisms is one of the essential nature of life.These channels play an important role in various life activities,such as maintaining cell osmotic balance and stabilizing cell volume.Inspired by this natural phenomenon,scientists have developed biomimetic nanodevices for sensitive sensing and biosensing,among which biological or artificial solid-state nanopore-based single-molecule analytics have attracted enormous research interest.Compared with biological nanopores,solid state nanoporeshave stable physical and chemical properties,easy to modify,and can be prepared with a variety of sizes.Recently,scientists have used glass nanopore confinement effect to detect the life activity of single cells.In this paper,we studied and analyzed the surface charge of single nanoparticle during collision with nanopore,the translocation behavior of multi-arm DNA assembly,and succeeded in discrimination of different base groups of oligonucleotides,by using functional glass nanopores as sensing platforms.The details are as follows:(1)We used the Au@SiO2 nanoparticle with a size of 83.5±6.5 nm to collide with the glass nanopore with a size of about 40 nm.When the nanoparticle approaches the opening of the nanopore and collide,the current will change dramatically,and there is a good linear relationship between the current amplitude and applied voltage.In this system,the collision current signal is related to electrophoretic force,electroosmotic flow and electrostatic effect,in which electroosmotic flow plays a leading role in the collision process.Therefore,the collision current signal can reflect the charge state of the nanoparticle and the nanopore wall.If the size of the nanopore and the nanoparticle is kept the same,the charge of the nanopore and the pore wall can be distinguished by the current amplitude and the collision time of the nanoparticles.The study highlights the potential of single particle impact systems based on glass nanopore to analyze the surface charge of nanoparticles in solution.(2)The conformational changes of a single multi-arm DNA concatemers duringthetranslocation process were detected using glass nanopore with a diameter of about 15 nm.We studied the translocation behavior ofthe three-arm DNA concatemers and found that the three-arm DNA concatemers has a certain orientation in the process of translocation.It will pass through the glass nanopore with the form of one arm first and the other two following up.This is mainly related to the steric hindrance of the DNA concatemers.In addition,we found that there is a certain relationship between the number of arms and the translocation frequency of DNA concatemers.This is caused by the competition between the surface charge and the steric hindrance of the DNA concatemers.At the same time,the conformational changes of the three-arm DNA concatemersthrough the glass nanopore with different diameters were investigated by the frequency and profile of the current signal.The developed nanopore sensing platform is promising forinvestigatingthe structural change of DNA concatemers in the future.(3)In general,the translocation events of individual oligonucleotides can usually be achieved by using biological nanopore.Because of its relatively big size and fast translocation velocity,nanopipettes are not suitable for detection of individual oligonucleotide.In this paper,a simple and convenient method for in situ polymerization of dopamine(PDA)on glass nanopipettes was developed.The diameter of the functionalized nanopipettes was changed from 100 nm to 10-20 nm.Since PDA contains a variety of functional groups,such as 1,2-dihydroxybenzene,amino,imine,phenol,carboxyl and so on,the resultingPDA-functionalized nanopipettes are capable of sensitive detection of single short oligonucleotides.The interaction between oligonucleotide and PDA allows the recognition of A/T/C/G groups of oligonucleotide of the same length.The PDA-functionalizednanopipettes can also distinguish oligonucleotides of different lengths based on dwell time.