Abstract
Interfacing solid-state nanopores with biological systems has been exploited as a versatile analytical platform for analysis of individual biomolecules. Although clogging of solid-state nanopores due to nonspecific interactions between analytes and pore walls poses a persistent challenge in attaining the anticipated sensing efficacy, insufficient studies focus on elucidating the clogging dynamics. Herein, we investigate the DNA clogging behavior by passing double-stranded (ds) DNA molecules of different lengths through hafnium oxide(HfO2)-coated silicon (Si) nanopore arrays, at different bias voltages and electrolyte pH values. Employing stable and photoluminescent-free HfO2/Si nanopore arrays permits a parallelized visualization of DNA clogging with confocal fluorescence microscopy. We find that the probability of pore clogging increases with both DNA length and bias voltage. Two types of clogging are discerned: persistent and temporary. In the time-resolved analysis, temporary clogging events exhibit a shorter lifetime at higher bias voltage. Furthermore, we show that the surface charge density has a prominent effect on the clogging probability because of electrostatic attraction between the dsDNA and the HfO2 pore walls. An analytical model based on examining the energy landscape along the DNA translocation trajectory is developed to qualitatively evaluate the DNA–pore interaction. Both experimental and theoretical results indicate that the occurrence of clogging is strongly dependent on the configuration of translocating DNA molecules and the electrostatic interaction between DNA and charged pore surface. These findings provide a detailed account of the DNA clogging phenomenon and are of practical interest for DNA sensing based on solid-state nanopores.
Highlights
Nanopores have emerged as a special class of single-molecule analytical tool that offers immense potential for sensing and characterizing biomolecules such as nucleic acids and proteins.[1−3] Typically, the nanopore measurement involves applying an external bias voltage to electrophoretically and/or electroosmotically drive biomolecules through nanopores in an insulating membrane
An added advantage with solid-state nanopores (SSNPs) is the compatibility of their fabrication with control electronics as well as optical measurement structures.[11−13] One major limitation of SSNPs is the nonspecific interaction between biomolecules and their sidewalls,[14,15] which is an outcome of hydrophobic interaction,[16,17] electrostatic attraction,[18,19] and van der Waals forces.[20,21]
The hydrophobic interaction or van der Waals forces between DNA and pore surface may still lead to pore clogging. These findings suggest that the DNA clogging probability can be modulated by altering the electrolyte pH, whereas it is affected by two distinct manners: (i) the strength of electrostatic attraction influenced by the surface charge density and (ii) the direction of electroosmotic flow (EOF) dragging force determined by the surface charge polarity
Summary
Nanopores have emerged as a special class of single-molecule analytical tool that offers immense potential for sensing and characterizing biomolecules such as nucleic acids and proteins.[1−3] Typically, the nanopore measurement involves applying an external bias voltage to electrophoretically and/or electroosmotically drive biomolecules through nanopores in an insulating membrane. An added advantage with SSNPs is the compatibility of their fabrication with control electronics as well as optical measurement structures.[11−13] One major limitation of SSNPs is the nonspecific interaction between biomolecules and their sidewalls,[14,15] which is an outcome of hydrophobic interaction,[16,17] electrostatic attraction,[18,19] and van der Waals forces.[20,21] These contributing forces can lead to adhesion of biomolecules and clog of the pores, which adversely affect the detection of molecule translocation and the sensing reliability
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