A High Spatiotemporal Iontronic Single-Cell Viscometer

Abstract

Ideal single-cell viscometer has remained unachieved, leaving a gap in current palette of single-cell nanotools. Information of single-cell viscosity could contribute to our knowledge of fundamental biological processes, e.g., mass diffusion, biochemical interaction, and cellular responses to many diseases and pathologies. Although advances have been made to this end, existing methods generally suffer from limitations, e.g., low spatiotemporal resolution. Here, we describe a high spatiotemporal iontronic single-cell viscometer that operates upon a patch clamp integrated with double-barreled nanopores separated by a septum of ca. 32 nm. The system enables reversible electroosmotic manipulation of the adjacent small fluid bridging two nanopores, the viscous alternation of which could be sensitively monitored by the ionic responses. In practical cellular studies, significantly, our findings reveal not only the less deviated medium viscosities than those of lysosomes and mitochondria but also the highest viscosities in the near-nuclear region than those of mitochondrion-dense and lysosome-dense regions. This work has provided an accessible single-cell viscometer and enriched the armory of single-cell nanotools.

Iontronic Sensing Based on Confined Ion Transport

“…The viscous alteration of this fluid was sensitively monitored through the ionic responses, as depicted in Figure 6E. 248 In a recent development, Wang et al introduced a nanoelectrochemical system, combining clustered regularly interspaced short palindromic repeat (CRISPR)/Casnanopipette technology for highly sensitive microRNA detection (Figure 6F). The nanoconfinement of CRISPR/ Cas13a within the nanopipette resulted in an exceptionally high catalytic efficacy, approximately 169 times higher than that in bulk electrolyte, leading to amplified electrochemical responses.…”

θ-Nanopore Ratiometry

“…Different from the single-barrel nanopipette, − double-barrel θ-nanopores, with two adjacent nanopores on one nanotip, have attracted interest across diverse sectors (Table S2) especially in single-cell studies. For example, Ivanov et al have developed θ-nanopores into nanotweezers for single-cell biopsies .…”

Alkaline Phosphatase-Mediated Bioetching of CoOOH/BiVO4 for Signal-On Organic Photoelectrochemical Transistor Bioanalysis

“…For example, Liu et al introduced energy transfer-based PEC sensors for in vivo monitoring neurochemicals in the brain; Fu and Zhang reported a synergistic resonance-mediated PEC system to real time recognize tumor cells in the mouse tail; and Dai et al constructed a switchable dual-modal colorimetric and PEC biosensing platform for DNA analysis . More recently, we engineered nanopipettes − into nanoscale PEC electrodes , toward intracellular probing down to single-cell levels. However, one major problem was still concentrated on its intrinsic inability to amplify signals.…”