Reversible Cation Response with a Protein-Modified Nanopipette

Abstract

b S Supporting Information E lectrical devices that can measure ion current through a nanopore are gaining attention as a new way to design sensors with nanoscale resolution. 1,2 Receptors immobilized to nanopore-based ion current sensors have included proteins, 3À5 enzymes, 6 DNA, 7 aptamers, 8 ligands, 9,10 and small biomolecules, 11,12 allowing nanoscale measurement of a variety of analytes. Sensing by modulation of ion current in functionalized nanopores is distinct from the technique of resistive-pulse sensing, which is used to characterize macromolecules by translocation through a pore. 13 To distinguish this mechanism in functionalized nanopipette sensors, 14 we coined the term signal transduction by ion nanogating (STING), evoking both the role of ion current and the needlelike shape of the nanopipette. Essential to the sensitivity of many solid-state nanopore sensors is selective permeability of electrolytes, or ion current rectification, when a bias is applied across the nanopore. Ion current rectification (ICR) arises from the selective interaction between ions in solution and the surface of a charged, asymmetrically shaped nanochannel or conical nanopore. 15 Nanomaterials exhibiting ICR and used as sensors include track-etched nanopores in polymer membranes 16 and quartz nanopipettes. 17 In either case, the surface modification of nanopores with appropriate receptors is a key challenge to sensor development.To date, the reversible binding of analytes with nanopore sensors has proven challenging. However, this is a critical issue if such devices are to be used for applications such as continuous monitoring or repeated measurements with one sensor. Multiple uses for a single sensor will also overcome problems in reproducible nanopore fabrication, which limits quantitative measurements for many sensors reported in the literature. For applications using

Probing the size of proteins with glass nanopores

“…24,25 Their fabrication is fast, cost-effective, and does not require a clean room. [26][27][28] Moreover, they can be easily combined with optical tweezers and segmented flow microfluidics which opens novel avenues to measure forces and develop new lab-on-the-chip applications. [29][30][31][32][33][34] In the beginning, classical solid-state nanopores and glass nanocapillaries were used to detect DNA.…”

Carbohydrate-actuated nanofluidic diode: switchable current rectification in a nanopipette

“…13 By using chemical receptors, solid-state nanopores have been engineered to respond to stimuli such as nucleic acids, 14 proteins, 15 small molecules, 16 and metal ions. 17, 18, 19, 20 As with binding of metal ions, the most sensitive and reversible systems are those in which the stimulus modulates surface charge within the nanopores. This is true for pH-responsive nanopores, prepared by attaching acidic or basic moieties onto pore walls and causing current rectification to be modulated with protonation state.…”

Ionic Current Rectification in Organic Solutions with Quartz Nanopipettes

“…Baker et al 22 have suggested that ICR could be enhanced or reduced through the electrostatic interactions between a neutral or a charged nanopipette and a charged substrate. In addition, many others have modified the surface of pipettes to explore the ICR phenomenon with different types of polymers, such as polylysine, 23 poly(acrylic acid), 24 chitosan, 25 and polymine. 26 Currently, almost all of the studies about ICR have been carried out in aqueous solutions, and mostly using KCl as the electrolyte; 26 only a few solvents other than water have been involved.…”