Rational Design of Stimuli-Responsive Polymers Modified Nanopores for Selective and Sensitive Determination of Salivary Glucose

Abstract

The great pain and stress from finger-prick glucose measurements have resulted in great motivation to find noninvasive glucose monitoring technologies where salivary glucose measurement is desirable. However, the relative low concentration of glucose and coexisting chemicals in saliva challenges the sensitive and selective salivary glucose detection. In this article, we have rationally designed and constructed a salivary glucose sensor by modifying the inner wall of the Au-decorated glass nanopore with stimuli-responsive copolymer poly­(3-(acryloylthioureido) phenylboronic acid-co-N-isopropylacrylamide) (denoted as PATPBA-co-PNIPAAm) via Au–S interaction. Notably, upon recognition of glucose, the copolymer could undergo a wettability switch and pKa shifts in the boronic acid functional groups, which significantly regulated the ion transport through nanopores, thus showing improved sensitivity with the detection limit of 1 nM. Moreover, benefiting from the multivalent boronic acid–glucose interaction and the cooperation of thiourea units, the copolymer exhibited good selectivity for glucose detection against the coexisting saccharides and other biological molecules in saliva. The nanopores with well-demonstrated analytical performance were finally applied for monitoring glucose in saliva. Together, this work unveiled a new platform for glucose detection in saliva, and promised to provide a new strategy for detecting other biomolecules in accessible biofluid involved in physiological and pathological events.

Coordination of Ligand-Protected Metal Nanoclusters and Glass Nanopipettes: Conversion of a Liquid-Phase Fluorometric Assay into an Enhanced Nanopore Analysis

“…Taking advantage of the dual signal change (fluorescence and surface charge) for the BSA–Au NC film, dual-modal detection of biothiols based on the BSA–Au NC film-modified glass nanopore was readily developed. Because the ionic current rectification behavior of the conical nanopore is susceptible to the inner surface charge, in this work, the rectification coefficient ( r = ln| I + / I – |, where I + and I – are the absolute value of current recorded at +1 and −1 V) can be used to monitor the modification process. , First, the conical glass nanopores with the orifice dimensions of ∼70 nm were produced (Figure S8). As shown in Figure S9, the unmodified glass nanopore displayed a negative current rectification ( r = −0.59) because its surface with hydroxyl groups was negatively charged in PBS (pH 7.0).…”

Boronic Acid‐containing Stimuli‐responsive Polymers Modified Nanopores for Label‐free Dual‐signal‐output Detection of Glucose

“…Besides the conformation and wettability changes, the binding of glucose to the copolymer also altered the pK a value of ATPBA groups [32]. When tested in a buffer solution at pH 9.0, the copolymers PATPBA-co-PNI-PAAm would transform to polyanions after recognizing glucose [29]. Hence, the positively charged pyrene probes might aggregate near the polyanions due to the electrostatic interaction.…”

“…Boronic acidcontaining stimulus-responsive polymers are especially interesting because not only the morphology of the polymer will transform, but the charges it carries will also make a difference upon molecular recognition [27,28]. After being combined with glucose at pH 9, the polymers will swell and become a polyanion [29]. This is because the initial pK a of phenyl boronic acid is ~8.8.…”

“…After binding to glucose, the pK a value will drop by 2-4 pH units [30]. The polymers have been exploited by us to regulate the ion transfer through the glass nanopore [29]. On the other hand, cationic pyrene may be assembled onto the glucose-bound anionic polymer, and the pyrene excimer emission can be detected due to the π-π stacking of the planar pyrene rings.…”

Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration

“…A variety of beneficial characteristics of MSCs can be maintained in 3D culture because the interactions of cell-to-cell and cell-to-matrix can be maintained better in a 3D environment [13]. Among cell scaffolds, gels and spheroid fusion, the 3D spheroids have attracted widespread attention in terms of uniform cell distribution, high fusion potential, and closeness to the natural cell microenvironment [14][15][16].…”