Flexible Point-of-Care Electrodes for Ultrasensitive Detection of Bladder Tumor-Relevant miRNA in Urine

Abstract

Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I−III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

Microfluidic Chips Fabrication and Integration for Tumor‐Derived Exosomes Detection

“…[43] Chen et al achieved POCT diagnosis of Bladder Tumor-Relevant miRNA-21 by a flexible electrochemical device. [44] However, miRNAs have the characteristics of short sequence and strong similarity. It is urgent to develop specific and highspeed detection methods.…”

Identification and detection of microRNA kidney disease biomarkers in liquid biopsies

“…Our laboratory has used the ferri/ferrocyanide redox system to provide electrochemical readouts and generated robust data from reusable glassy carbon electrodes (limit of detection of 20 fM) [46], and disposable screenprinted electrodes (17 fM) [47], successfully recapitulating urinary miRNA RT-qPCR data from people with DKD [46,47]. Chen et al [48] produced flexible single-walled carbon nanotube electrodes to which they bound DNA complementary to miR-21, a biomarker of bladder cancer. They then hybridised the sensor with target miR-21 before addition of exogenous methylene blue reporter.…”

“…They then hybridised the sensor with target miR-21 before addition of exogenous methylene blue reporter. These workers achieved a limit of detection of 3 fM, and monitored urinary miR-21 to successfully distinguish between prostate and bladder cancer patients compared with controls [48].…”

A bimetallic metal–organic framework with high enzyme-mimicking activity for an integrated electrochemical immunoassay of carcinoembryonic antigen

“…16,17 For example, Chen et al reported an integrated flexible electrode for the rapid detection of cancer-related RNA in human urine samples with excellent sensitivity and stability. 18…”