Changes In Electrochemical Signals Research Articles

Electrochemical response mechanism of DNA damaged cells: DNA damage repair and purine metabolism activation

In modern society, due to the sharp increase in pollutants that cause DNA damage, there is a growing demand for innovative detection techniques and biomarkers. In this paper, the electrochemical behavior of HepG2 cells exposed to CdCl2 was investigated, and the electrochemical response mechanism of DNA damage was identified by exploring the correlation between the DNA damage response and purine metabolism. Western blot analysis revealed that the expression levels of ATM and Ku70 increased at 0.3 μM CdCl2, indicating a DNA damage response and activation of DNA repair processes. Simultaneously, elevated expression levels of PRPP aminotransferase, HPRT, and XOD were observed, leading to an increase in intracellular purine levels and electrochemical signals. The expression of Ku70 peaked at 0.5 μM CdCl2, indicating the highest DNA repair activity. The expression profiles of these purine metabolism proteins mirrored those of Ku70, suggesting a strong correlation between the activation of purine metabolism and DNA damage repair. Consistently, intracellular purine levels exhibited a similar trend, leading to corresponding changes in electrochemical signals. In summary, electrochemical using intracellular purines as biomarkers has the potential to emerge as a novel method for detecting early DNA damage.

Dual-mode iodine sensing: Colorimetric and electrochemical detection methods using functionalized gold nanoparticles

Iodine in natural and treated waters exists mainly as iodide, iodate, and molecular iodine (I2). I2 is a highly volatile and reactive species impacting biological and chemical systems. Iodine, a vital micronutrient, is essential for human and animal growth and metabolism. It also plays a crucial role in synthesising artificial adrenaline within the metabolic processes of humans and animals. It is also widely used as an antiseptic, disinfectant, and for emergency water disinfection. Moreover, iodine deficiency can result in various diseases, especially hypothyroidism and goitre. Given its critical functions, it is imperative to have a straightforward, dependable, and efficient method for monitoring iodine levels. This study introduces a simple and innovative I2 detection system based on its reactivity, toxicity, and role as an indicator of oxidative conditions in water. It operates in terms of based on optical and electrochemical signal changes, utilising the anti-aggregation mechanism of gold nanoparticles (AuNPs) and 6-mercaptohexanol (MHA) for sensitive and selective detection under mild conditions. I2 determination is achieved by observing the colour change in AuNPs, which is influenced by competitive interactions between MHA, I2, and AuNPs. The optical detection system, with its low detection limit (LOD=260 nM), is based on the straightforward observation of colour changes. On the other hand, the electrochemical detection method utilises changing redox peaks observed in anodic region, providing selective and sensitive I2 detection (LOD=100 nM). The probe effectively detects the presence of I2 in real water samples as a practical application. Moreover, the proposed method revolutionises I2 detection by incorporating a smartphone for signal reading, eliminating the need for specialised equipment and significantly reducing the detection cost. This cost-effective approach carries the potential to expedite on-site and naked-eye I2 detection, opening up new possibilities for research and application.

Tracking epithelial-mesenchymal transition in breast cancer cells based on a multiplex electrochemical immunosensor

Epithelial-mesenchymal transition (EMT) promotes tumor cell infiltration and metastasis. Tracking the progression of EMT could potentially indicate early cancer metastasis. A key characteristic of EMT is the dynamic alteration in the molecular levels of E-cadherin and N-cadherin. Traditional assays have limited sensitivity and multiplexing capabilities, relying heavily on cell lysis. Here, we developed a multiplex electrochemical biosensor to concurrently track the upregulation of N-cadherin expression and reduction of E-cadherin in breast cancer cells undergoing EMT. Small-sized gold nanoparticles (Au NPs) tagged with redox probes (thionin or amino ferrocene) and bound to two types of antibodies were used as distinguishable signal tags. These tags specifically recognized E-cadherin and N-cadherin proteins on the tumor cell surface without cross-reactivity. The diphenylalanine dipeptide (FF)/chitosan (CS)/Au NPs (FF-CS@Au) composites with high surface area and good biocompatibility were used as the sensing platforms for efficiently fixing cells and recording the dynamic changes in electrochemical signals of surface proteins. The electrochemical immunosensor allowed for simultaneous monitoring of E- and N-cadherins on breast cancer cell surfaces in a single run, enabling tracking of the EMT dynamic process for up to 60 h. Furthermore, the electrochemical detection results are consistent with Western blot analysis, confirming the reliability of the methodology. This present work provides an effective, rapid, and low-cost approach for tracking the EMT process, as well as valuable insights into early tumor metastasis.

Enhanced sensitivity in electrochemical detection of ochratoxin A within food samples using ferrocene- and aptamer-tethered gold nanoparticles on disposable electrodes.

Ensuring food security is crucial for public health, and the presence of mycotoxins, produced by fungi in improperly stored processed or unprocessed food, poses a significant threat. This research introduces a novel approach - a disposable aptasensing platform designed for the detection of ochratoxin A (OTA). The platform employs gold-nanostructured screen-printed carbon electrodes functionalized with a ferrocene derivative, serving as an integrated faradaic transducing system, and an anti-OTA aptamer as a bioreceptor site. Detection relies on the ferrocene electrochemical signal changes induced by the aptamer folding in the presence of the target molecule. Remarkably sensitive, the platform detects OTA within the range of 0.5 to 70 ng mL-1 and a detection limit of 11 pg mL-1. This limit is approximately 200 times below the levels stipulated by the European Commission for agricultural commodities. Notably, the sensing device exhibits efficacy in detecting OTA in complex media, such as roasted coffee beans and wine, without the need for sample pretreatment, yielding accurate recoveries. Furthermore, while label-free electrochemical aptasensors have proliferated, this study addresses a gap in understanding the binding mechanisms of some aptasensors. To enhance the experimental findings, a theoretical study was conducted to underscore the specificity of the anti-OTA aptamer as a donor for OTA detection. The molecular docking technique was employed to unveil the key binding region of the aptamer, providing valuable insights into the aptasensor specificity.

A Novel Triazolopyrimidinone Derivative: A Portable Electrochemical Approach to Investigate DNA Interactions

In this study, a novel triazolopyrimidinone derivative, 2-(2-chlorophenyl)-5-(morpholinomethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one, abbreviated as CPD-1, was synthesized as a drug candidate. By employing electrochemical techniques, we analyzed the electrochemical behavior of this compound and its interactions with both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Experimental parameters such as pH, concentration, scan rate, immobilization time were studied using Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV) to obtain the most precise analytical signals. We present an innovative approach to evaluate the toxicity effect of this drug candidate on DNA. We also propose a simplified equation to quantify toxicity effects based on changes in electrochemical signals, specifically peak current of guanine bases, before and after drug-DNA interactions. Our methodology contributes to the burgeoning field of electrochemical toxicity assessment and holds promise for advancing drug development and safety evaluation. Furthermore, stability tests for the drug candidate were conducted on different days. Notably, our investigation revealed significant alterations in guanine bases upon the interaction of CPD-1 with both ssDNA and dsDNA, underscoring the potential impact of these compounds on DNA structure. Based on our experimental data, we conclude that this molecule can be utilized as a drug due to its effects on DNA.

Assessment of oxygenated polycyclic aromatic hydrocarbon cytotoxicity using TiO2-MXene/MWCNTs/PDA/GCE electrochemical sensor

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) present in the environment can enter the skin through direct contact and long-term exposure can increase the risk of skin inflammation, allergic reactions and skin cancer. In this study, a titanium dioxide-two-dimensional transition metal carbide/multi-walled carbon nanotubes/polydopamine/glassy carbon electrode (TiO2-MXene/MWCNTs/PDA/GCE) electrochemical biosensor was prepared to evaluate the cytotoxicity of OPAHs based on the changes in the content of xanthine/guanine (X/G) during cellular metabolism. The TiO2-MXene/MWCNTs/PDA/GCE exhibited excellent electrocatalytic activity and sensitivity. The surface morphology, structure and electrochemical properties of TiO2-MXene/MWCNTs/PDA composite material were characterized using scanning electron microscopy, X-ray diffraction and cyclic voltammetry. Human skin fibroblast cells (HFF-1) were used as model cells, and the cell viability was evaluated based on the electrochemical signal changes of X/G. When exposed to OPAHs for 30 h, the half-maximal inhibitory concentrations (IC50) of 1,4-benzoquinone (1,4-BQ), 1,2-naphthoquinone (1,2-NQ), and 9,10-phenanthrenequinone (9,10-PQ) on HFF-1 cells were 291.88, 67.72, and 4.44 µmol·L−1, respectively, which were lower than the IC50 values of 1075.51, 113.96, and 9.63 µmol·L−1 obtained using the traditional MTT assay, indicating higher sensitivity of the sensor. This study achieved sensitive detection of purines in HFF-1 cells, providing a technical method for evaluating the cytotoxicity of persistent organic pollutants OPAHs in the environment.

Magnetically induced self-assembly electrochemical biosensor with ultra-low detection limit and extended measuring range for sensitive detection of HER2 protein

An innovative electrochemical biosensor was fabricated for sensitive detection of human epidermal growth factor receptor 2 (HER2) protein, which was considered as an essential tumor marker for diagnosis and treatment evaluation of breast cancer. The sensor was constructed using Apt and PNA as recognition probes incorporated with magnetic Fe3O4/α-Fe2O3@Au nanocomposites. The sensing strategy was designed to lower the detection limit of HER2, and avoid the large steric interference caused by macromolecular HER2 on the electrode surface. Rigid structure dsDNA (Apt/ssDNA) was designed to improve the sensitivity of the sensor. Apt captured the macromolecular HER2 protein, and ssDNA chains were simultaneously released, causing a sensitive change in the electrochemical signal. PNA captured the released ssDNA chains, which converted the electrochemical signal changes caused by HER2 to those caused by the number of short strand ssDNA, so the detection range was extended. Under optimized conditions, this sensing strategy realized an ultra-low detection LOD of HER2 (4.1 fg·mL−1), and the detection range was 10 fg·mL−1–5 × 106 fg·mL−1. The experimental results confirmed that the electrochemical biosensor had excellent selectivity, reproducibility, and storage stability. Analysis of spiked serum samples exhibited a recovery rate of 95.9–115.7 %, which indicated great promise for HER2 detection in serum samples.

Concentration analysis of metal-labeled nanoplastics in different water samples using electrochemistry

Despite the threats posed by nanoplastics to the environment and human health, little was known about the occurrence, formation, migration, and environmental impacts of nanoplastics due to the lack of quantitative and sensitive detection techniques. In this work, an electrochemical strategy for the detection of nanoplastics based on Ag labeling was proposed. Positively charged silver ions were attached to negatively charged polystyrene nanoplastics (PSNPs), and then the silver ions on the surface of PSNPs were reduced to Ag by sodium borohydride. Subsequently, the concentration of PSNPs was determined by identifying the signal of Ag by differential pulse voltammetry. The method showed different sensitivity for PSNPs of different sizes (100, 367, 500 nm). For tap water samples, the reason for the change in Ag electrochemical signal was discussed. The sensitivity of the method to PSNPs in tap water was investigated. The feasibility of the method for environmental water samples was verified using spiked lake water and spiked seawater, and satisfactory recoveries (93–112 %) were obtained for PSNPs of different sizes and concentrations. This study provided a sensitive, low-cost, and simple method without complex instrumentation, which was important for the determination of PSNPs in environmental water samples.

Programmable electrochemical biosensing platform based on catalytic hairpin assembly and entropy-driven catalytic cascade amplification circuit

Herein, powerful DNA strand displacement reaction and sensitive electrochemical analysis method were ingeniously integrated to develop a programmable biosensing platform. Using DNA as the detection model, a cascade amplification system based on catalytic hairpin assembly and entropy-driven catalytic was constructed, and the reaction rate and signal amplification effect were significantly improved. The product of the cascade amplification circuit could undergo strand displacement reaction with the signal probe on the electrode surface to obtain sensitive electrochemical signal changes and realize highly sensitive detection of the target. In addition, without redesigning the DNA sequences in the cascade amplification circuit, the by-product strand typically wasted in traditional entropy-driven catalytic reactions can be fully utilized to construct a single-signal output biosensing system and even a dual-signal output ratiometric biosensing platform, improving the detection repeatability and reliability of the system, and expanding the application of DNA strand displacement reaction in electrochemical biosensing. Furthermore, benefiting from the design flexibility of the DNA molecules, the constructed biosensing platform realized the sensitive detection of aptamer substrate (kanamycin as an example) and certain metal ion (mercury as an example) by simply recoding the corresponding recognition sequence, demonstrating the good versatility of the biosensing platform.

High-sensitive and rapid electrochemical detection of miRNA-31 in saliva using Cas12a-based 3D nano-harvester with improved trans-cleavage efficiency

Salivary miRNA-31 is a reliable diagnostic marker for early-stage oral squamous cell carcinoma (OSCC), but accurate detection of miRNA-31 in saliva samples is a challenge because of its low level and high sequence homology. The CRISPR/Cas12a system has the exceptional potential to enable simple nucleic acid analysis but suffers from low speed and sensitivity. To achieve rapid and high-sensitive detection of miRNA-31 using the CRISPR/Cas12a system, a Cas12a-based nano-harvester activated by a polymerase-driven DNA walker, named as dual 3D nanorobots, was developed. The target walked rapidly on the surface of DNA hairpin-modified magnetic nanoparticles driven by DNA polymerase, generating numerous double-strand DNA (dsDNA). Then, the Cas12a bound to the generated dsDNA for activating its trans-cleavage activity, forming 3D nano-harvester. Subsequently, the harvester cut and released methylene blue-labeled DNA hairpins immobilized on the sensing interface, leading to the change in electrochemical signal. We found that the trans-cleavage activity of the harvester was higher than the conventional CRISPR/Cas12a system. The developed dual 3D nanorobots could enable rapid (detection time within 60 min), high-sensitive (detection limit of femtomolar), and specific analysis of miRNA-31 in saliva samples. Thus, our established electrochemical biosensing strategy has great potential for early diagnosis of OSCC.

Aerosol Jet Printing-Enabled Dual-Function Electrochemical and Colorimetric Biosensor for SARS-CoV-2 Detection.

An aerosol jet printing-enabled dual-function biosensor for the sensitive detection of pathogens using SARS-CoV-2 RNA as an example has been developed. A CRISPR-Cas13:guide-RNA complex is activated in the presence of a target RNA, leading to the collateral trans-cleavage of ssRNA probes that contain a horseradish peroxidase (HRP) tag. This, in turn, catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by HRP, resulting in a color change and electrochemical signal change. The colorimetric and electrochemical sensing protocol does not require complicated target amplification and probe immobilization and exhibits a detection sensitivity in the femtomolar range. Additionally, our biosensor demonstrates a wide dynamic range of 5 orders of magnitude. This low-cost aerosol inkjet printing technique allows for an amplification-free and integrated dual-function biosensor platform, which operates at physiological temperature and is designed for simple, rapid, and accurate point-of-care (POC) diagnostics in either low-resource settings or hospitals.

Fabrication of metal–organic framework based electrochemical Leishmania immunosensor

Leishmaniasis is a disease with a high impact on public health in many countries. In this study, an electrochemical immunosensor for Leishmania major surface protease (Gp63) antibody detection was developed using copper metal organic framework (Cu-(NH2-BDC)-MOF) modified gold screen printed electrode (AuSPE). For this purpose, after modification step of AuSPE with Cu-(NH2-BDC)-MOF, recombinant L.donovani antigen was immobilized on to electrode surface via crosslinker where change in electrochemical signal was monitored with electrochemical impedance spectroscopy technique. After conducting comprehensive optimization studies on experimental parameters of developed Leishmania immunosensor, analytical characteristics were searched. As a result, it was observed that anti-gp63 solution diluted up to the ratio of 1:1500 could be detected with the developed sensor. Meanwhile, relative standard deviation value was found as 4.67% for anti-gp63 diluted in the ratio of 1:80 (n = 3). Accordingly, real sample analysis was also performed by using Leishmania parasite crude antigen and rabbit serum which were positive and negative control samples, respectively. According to the results obtained, it can be concluded that a practical immunosensor that can allow the early diagnosis of leishmaniasis was developed.

Electrochemical Cellulase-Linked ELASA for Rapid Liquid Biopsy Testing of Serum HER-2/neu.

Non-invasive liquid biopsy assays for blood-circulating biomarkers of cancer allow both its early diagnosis and treatment monitoring. Here, we assessed serum levels of protein HER-2/neu, overexpressed in a number of aggressive cancers, by the cellulase-linked sandwich bioassay on magnetic beads. Instead of traditional antibodies we used inexpensive reporter and capture aptamer sequences, transforming the enzyme-linked immuno-sorbent assay (ELISA) into an enzyme-linked aptamer-sorbent assay (ELASA). The reporter aptamer was conjugated to cellulase, whose digestion of nitrocellulose film electrodes resulted in the electrochemical signal change. ELASA, optimized relative aptamer lengths (dimer vs monomer and trimer), and assay steps allowed 0.1 fM detection of HER-2/neu in the 10% human serum in 1.3 h. Urokinase plasminogen activator and thrombin as well as human serum albumin did not interfere, and liquid biopsy analysis of serum HER-2/neu was similarly robust but 4 times faster and 300 times cheaper than both electrochemical and optical ELISA. Simplicity and low cost of cellulase-linked ELASA makes it a perspective diagnostic tool for fast and accurate liquid biopsy detection of HER-2/neu and of other proteins for which aptamers are available.

Immunosensor fabrication methods: A scoping review

Various methods of establishing a diagnosis, especially for initial diagnosis, have been widely developed, such as Rapid Diagnostic Test (RDT), Enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR). However, those tools have several different limitations in each tool. The limitations of this tool include a fairly high error rate and the need for complex tools. The work can only be used by special personnel and a long processing time. Immunosensors are tools that can be used as an alternative. Immunosensor is a sensor used to detect specific immune reactions between antibodies and targets in the form of antigens and can detect interactions between analyte targets and antibodies from changes in electrochemical signal, sot the examination time is relatively faster. This scoping review aims to review each immunosensor fabrication parameter. The results proved that each analyte has a different characterization and is very diverse. So it is necessary to select the right parameters (electrode type, immunoassay configuration, electrode modification, receptor immobilization, and electrochemical characterization). The linear range and detection limit are also important parameters that can be developed so that very limited analyte concentrations in the sample can be detected. It is necessary to review fabrication methods to improve the stability of immunosensors so that the ligands contained in the immunosensor electrodes can last a long time to be able to carry out mass production.

Ultrafast Biomarker Quantification through Reagentless Capacitive Kinetics.

We introduce a facile assessment of binding kinetics at bioreceptive redox-active interfaces as a means of quantifying target proteins. This is achieved by monitoring the redox capacitance (Cr) of a receptor-modified conductive polymer interface under continuous flow. Exemplified with the quantification of C-reactive protein (CRP), capacitance analyses resolve both the association and dissociation regimes in real-time. Significantly, the rate of electrochemical signal change within the association regime is a sensitive function of target concentration, enabling marker assaying down to picomolar levels, comparable to end-point assays, in 15 s. This reagentless proof-of-principle methodology is envisioned to be widely applicable to the facile quantification of a range of other pertinent, clinically relevant targets.

A duplex-specific nuclease based electrochemical biosensor for the assay of SARS-CoV-2 RdRp RNA

We present a method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection based on the dual amplification effect of duplex-specific nuclease (DSN). In this scheme, we cleverly employed a 2-OMe-RNA modified DNA to prevent hairpin nucleic acid from being digested by DSN. The target RNA and 2-OMe-RNA are released when DSN cleaves just the double-stranded RNA/hairpin nucleic acid DNA. The target RNA then forms a circular reaction when it hybridizes with another hairpin nucleic acid. Simultaneously, the released target 2-OMe-RNA turns on the hairpin DNA2 on the electrode surface, and when the DSN cleaves the DNA in the hairpin DNA2/2-OMe-RNA duplex, the 2-OMe-RNA is released and hybridized with the other hairpin DNA2. The hairpin DNA2 on the electrode surface is split off after many cycles, exposing the gold electrode surface. As a consequence, there is more K4[Fe(CN)6]/K3[Fe(CN)6] redox near to the electrode surface, and the electrochemical signal increases. As a result, the change in electrochemical signal may be used to calculate the quantity of RNA that has to be measured. The protocol has good sensitivity in the detection of SARS-CoV-2: the detection limit reached 21.69 aM. This protocol provides an effective solution for the highly sensitive screening of SARS-CoV-2.

CoNi-RGO and NiCo2S4-ZIF/g-C3N4 signal amplified electrochemical immunosensors for sensitive detection of CYFRA 21-1

Herein, a signal amplified electrochemical immunosensor for the sensitive detection of cytokeratin 19 fragments (CYFRA 21-1) in human serum was discussed. The CoNi-RGO was used as a substrate for the sensor with excellent specific surface area and strong electrical conductivity, which enables more efficient attachment of antibodies. The introduction of the bimetallic sulfide NiCo2S4 composite ZIF material provides strong catalytic performance for the immunosensor. It is worth noting that, in addition to these satisfactory advantages, these two materials also show amazing signal amplification capacity. When the immunosensor works, the increase in electrical impedance decreases the electron transfer rate, making the electrochemical signal change obvious. The signal enhancement of immunosensors was emphasized by the marker during construction, and the experimental results were satisfactory. The proposed signal enhanced immunosensor had a linear relationship in the range of 0.001–10 ng/mL for CYFRA 21-1, and the minimum detection limit was 0.33 pg/mL for △I = 95.22 + 23.27 lg c. This demonstrates that the electrochemical immunosensor we constructed is successful and has a great developing potential.

Sensitive Dual Electrochemical-Colorimetric Point-of-Care (POC) Sensor for the Rapid Detection of Mycoplasma pneumoniae

Mycoplasma pneumoniae (M. pneumoniae) is a problem affecting the health of children and adolescents worldwide. Thus, there is a pressing need to construct a point-of-care (POC) method for the rapid detection of M. pneumoniae. In this work, a sensitive dual electrochemical-colorimetric POC sensor was constructed based on reduced graphene oxide (RGO) and a polyaniline (PANI) modified surface for the rapid diagnosis of M. pneumoniae. The POC sensor showed excellent performance with a sensitivity of 69.78 mV/pH. The pH measurement was minimally affected in the presence of interfering ions and the durability of the electrochemical sensor was 2.54 mV/d. The device was sensitive for M. pneumoniae from 102 copies/reaction to 105 copies/reaction and satisfactorily validated in 18 clinical specimens. The entire nucleic acid extraction and detection process was completed within 30 min which was 9 minutes less than the commercial fluorescence and colorimetric kits. More interestingly, the results were monitored by the electrochemical signal and solution color change. The results are expected to have a positive impact on the quantitative detection of M. pneumoniae and allow the rapid diagnosis of M. pneumoniae infections.

A specially designed DNA-assembled framework structure probe coupled with loop-mediated isothermal amplification (LAMP)-DNA signal transducer for rapid and sensitive electrochemical detection of miRNA

Herein, a new DNA-assembled framework structure (DAFS) probe coupled with LAMP-DNA signal transducer is developed for rapid and sensitive detection of miRNA let-7a. The DAFS probe was formed via self-assembly of capture strand (P) and ferrocene-labelled DNA strands (P1, P2) and was immobilized via hybridization of P1 and P2 with the DNA strands tethered to electrode surfaces. On the other hand, forward primer (FP) of LAMP was hybridized with assistant strand (AS) attached on Au@Fe3O4 composite nanoparticles. After LAMP reaction started, the duplex FP:AS was separated to expose the AS. Then, with a facile magnetic separation, the exposed AS was collected and further cut by Mn2+, outputting the signal transducer T *. The DAFS probe could disassemble by the T *in the presence of two hairpin DNA probes (H1, H2) and release the P1 and P2 into the solution, causing an electrochemical signal change for realizing sensitive detection of final target let-7a. The electrochemical detection could complete within 50 min with a good linear relationship from 100 aM to 20 pM and a detection limit of 48 aM. Our biosensors performed well in human serum spiked with the let-7a and the let-7a extracts obtained from the human breast cancer cell (MCF-7).

An electrochemical aptasensor with N protein binding aptamer-complementary oligonucleotide as probe for ultra-sensitive detection of COVID-19

The emergence of the COVID-19 epidemic has affected the lives of hundreds of millions of people globally. There is no doubt that the development of fast and sensitive detection methods is crucial while the worldwide effective vaccination programs are miles away from actualization. In this study, we have reported an electrochemical N protein aptamer sensor with complementary oligonucleotide as probe for the specific detection of COVID-19. The electrochemical aptasensor was prepared by fixing the double-stranded DNA hybrid obtained by the hybridization of N protein aptamer and its Fc-labeled complementary strand on the surface of a gold electrode. After incubation with the target, the aptamer dissociated from the labeled complementary DNA oligonucleotide hybrid to preferentially bind with N protein in the solution. The concentration of N protein was measured by detecting the changes in electrochemical current signals induced by the conformational transformation of the complementary DNA oligonucleotide left on the electrode surface. The sensor had a linear relationship between the logarithm of the N protein concentration from 10 fM to 100 nM (ΔIp = 0.098 log CN protein/fM - 0.08433, R2 = 0.99), and the detection limitation was 1 fM (S/N = 3). The electrochemical aptamer sensor was applied to test the spiked concentrations of throat swabs and blood samples from three volunteers, and the obtained results proved that the sensor has great potentials for the early detection of COVID-19 in patients.