Bioinspired Trans‐Scale Functional Interface for Enhanced Enzymatic Dynamics and Ultrasensitive Detection of microRNA

Abstract

Protein interactions with specific nucleic acid sequences are crucial in cell growth. Inspired by such binding events that often occur at nanoscale biointerface, here a trans‐scale functional interface capable of considerably enhancing in vitro DNA‐enzyme interaction is reported. Using a screen‐printed electrode with nanoroughened carbon surface, the high‐curvature gold nanostructures in a single electrodeposition step can be programmed. In this process, a synergistic effect is found between nanoroughened carbon and polyelectrolyte multilayer enabling the formation of high‐stability and high‐curvature nanostructures. More importantly, these fractal nanostructures effectively overcome neighboring probes aggregation at high density and allow the probes to be more freely accessed by target molecules. As compared to its planar counterparts, this nanostructuring interface demonstrates faster enzymatic dynamics that enables ultrasensitive detection of microRNA with a detection limit of 35 × 10−18 m. Such an efficient trans‐scale biosensing interface has also accurately differentiated the patients with rheumatic arthritis from the health ones, signifying its great potential in precision medicine.

Synergy of Peptide–Nucleic Acid and Spherical Nucleic Acid Enabled Quantitative and Specific Detection of Tumor Exosomal MicroRNA

“…This is because the nanoscale control (1.9 nm intermolecular spacing) of the “electroneutral” PNA assembly can improve molecular recognition efficiency by minimizing the steric hindrance and electrostatic repulsion. It is anticipated that the sensitivity could be further improved by integration with a high-curvature functional interface or microfluidics to meet the direct, unamplified sample detection on site. ,− …”

“…(iv) The SEEmiR sensor is enzyme-free and can operate at room temperature. We envisage that our sensor can be integrated readily with framework nucleic acid probes, trans-scale interface, single-step microfluidics, and/or magnetically or electrically accelerated hybridization to enable rapid and inexpensive detection of a wide range of clinical-related miRNAs for precision medicine. ,,− …”

“…Given the small size and low abundance of miRNA, many biosensing schemes have been devised to improve the probe design and signal readout for reliable ExomiR detection. , Usually, the fully complementary sequences are used as recognition probes to capture the target miRNAs for profiling. This design allows high-efficiency hybridization that maximizes the participation of short miRNA bases in sequence-specific recognition, whereas such full-match strategies often suffer from limited signal-enhancing means that rely on either enzymes (e.g., duplex-specific nuclease) or ultrasensitive transducers (e.g., nanopores, surface-enhanced Raman scattering, nanoplasmonic and field-effect transistors) to enhance detection sensitivity. − Partially hybridized toehold DNA-based branch migration provides another opportunity to enable enzyme-free signal-amplified detection of ExomiR. − These approaches often require “DNA walker” design or consecutive exposure of the toehold domain, which is necessary to drive cyclic signal amplification without enzyme. Nevertheless, these strategies are hampered by the sophisticated probe design, multiple labels, and the accurate control of dynamic equilibrium in reaction, especially in solution phase.…”

Integrated Microdroplets Array for Intelligent Electrochemical Fabrication

“…The gold nanostructures have attracted sustained attention in catalysis, sensing, and electronic field due to the diversified nanostructures 28–31. Electrochemical deposition is a traditional technique for fabricating gold nanostructures (e.g., nanoparticle, nanowires, nanoflowers, nanodendrites) 32–35. Therefore, we chose the electrochemical deposition of gold nanostructures as a model to verify feasibility and practicality of such platform.…”

Fabrication of a Free‐Standing MWCNT Electrode by Electric Field Force for an Ultra‐Sensitive MicroRNA‐21 Nano‐Genosensor

“…[6,7] For the detection of miR-21, several electrochemical biosensors have been proposed and showed the potential for diagnosing colorectal cancer at an early stage. [8][9][10][11][12][13] Meanwhile, electrochemical biosensors by modifying carbon nanotubes (CNTs, including single-walled CNTs and Multi-walled CNTs) or the other 1D-nanomaterials could improve the analytical performance for detecting miR-21 in sensitivity, selectivity, rapidity, and accuracy, due to high specific surface area. [14][15][16][17][18][19][20] Currently, CNTs were incorporated into the polymer to form modification materials for electrochemicalsignal amplification in CNT-modified biosensors.…”