Electrochemical Cytosensor Research Articles

Electrochemical cytosensor utilizing tetrahedral DNA/bimetallic AuPd holothurian-shaped nanoparticles for ultrasensitive non-destructive detection of circulating tumor cells.

As a real-time fluid biopsy method, the detection of circulating tumor cells (CTCs) provides important information for the early diagnosis, precise treatment, and prognosis of cancer. However, the low density of CTCs in the peripheral blood hampers their capture and detection with high sensitivity and selectivity using currently available methods. Hence, we designed a sandwich-type electrochemical aptasensor that utilizes holothurian-shaped AuPd nanoparticles (AuPd HSs), tetrahedral DNA nanostructures (TDNs), and CuPdPt nanowire networks (NWs) interwoven with a graphdiyne (GDY) sheet for ultrasensitive non-destructive detection of MCF-7 breast cancer cells. CuPdPt NW-GDY effectively enhanced the electron transfer rate and coupled with the loaded TDNs. The TDNs could capture MCF-7 cells with precision and firmness, and the resulting composite complex was combined with AuPd HSs to form a sandwich-type structure. This novel aptasensor showed a linear range between 10 and 106 cells mL-1 and an ultralow detection limit of 7 cells mL-1. The specificity, stability, and repeatability of the measurements were successfully verified. Moreover, we used benzonase nuclease to achieve non-destructive recovery of cells for further clinical studies. According to the results, our aptasensor was more sensitive measuring the number of CTCs than other approaches because of the employment of TDNs, CuPdPt NW-GDY, and AuPd HSs. We designed a reliable sensor system for the detection of CTCs in the peripheral blood, which could serve as a new approach for cancer diagnosis at an early stage.

Vertically ordered mesoporous silica film-assisted electrochemical cytosensor for the sensitive detection of HeLa cells.

Designing fast and simple quantitative methods on cheap and disposable electrodes for the early detection of HeLa cells is highly desirable for clinical diagnostics and public health. In this work, we developed a label-free and sensitive electrochemical cytosensor for HeLa cell detection based on the gated molecular transport across vertically ordered mesoporous silica films (VMSFs) on the disposable indium tin oxide (ITO) electrode. As high affinity for a folate receptor existed on the membrane of HeLa cancer cells, folic acid (FA) functionalized VMSF could regulate the transport of electrochemical probe (Fe(CN)6 3-) by the specific recognition and adhesion of HeLa cells toward the VMSF surface. In addition, VMSF, served as a solid skeleton, is able to effectively prevent the direct contact of cells with the underlying electrode, remaining the underlying electrode activity and favoring the diffusion of Fe(CN)6 3-. Once specific adhesion of HeLa cells to the VMSF surface happens, Fe(CN)6 3- redox probe exhibits impeded transport in the silica nanochannels, ultimately resulting in the decreased electrochemical responses and realizing the quantitative determination of HeLa cells with a broad linear range (101-105 cells/mL) and a low limit of detection (4 cells/mL). The proposed electrochemical cytosensor shows a great potential application for the early diagnosis of cervical cancer.

Early stage evaluation of cancer stem cells using platinum nanoparticles/CD133+ enhanced nanobiocomposite

BackgroundCancer stem cells (CSCs) are of great diagnostic importance due to their involvement in tumorigenesis, therapeutic resistance, metastasis and relapse.MethodIn this work, a sensitive electrochemical cytosensor was successfully established to detect HT-29 colorectal cancer stem cells based on a nanocomposite composed of mesoporous silica nanoparticles (MSNs) and platinum nanoparticles (PtNPs) using a simple and fast electrodeposition technique on a glassy carbon electrode (GCE).ResultsAccording to SEM images, the PtNPs nanoparticles formed on the MSNs substrate are about 100 nm. As expected, high-rate porosity, increased surface-to-volume ratio, provides appropriate local electron transfer rate and suitable platform for the efficient formation of PtNPs. These features allow direct and stable binding of biotinylated monoclonal antibody of CD133 to streptavidin (Strep) and the subsequent availability of active sites for CSCs identification. Differential pulse voltammetry (DPV) results show that close interaction of CD133+ cells with monoclonal antibodies reduces charge transfer and electrical current, as confirmed by square wave voltammogram (SWV). Based on the recorded current versus number of CSCs, we noted that our developed system can sense CSCs from 5 to 20 cells/5 μL.ConclusionsAs a proof of concept, the designed nanobiocomposite was able to specifically detect CD133+ cells compared to whole HT-29 cells before magnetic activated cell sorting (MACS) process.

A three-site recognition cytosensor based on multi-active AuIrPt polyhedral nanozymes for detection of CTCs

We developed a novel electrochemical cytosensor based on AuIrPt nanozymes and three-site recognition strategy for the detection of specific CTCs. Using pluronic F127 as the organic framework, new trimetallic AuIrPt nanozymes with exceptional multiple enzyme-like activities were synthesized, which could mimic the activities of three enzymes, SOD, POD, and CAT. Nanozymes linked with EpCAM (Epithelial cell adhesion molecule) aptamers served as signal tags to enhance sensitivity of the cytosensor, and anti-MUC1 (Mucin 1) and anti-EGFR (Epidermal growth factor receptor) antibodies for isolation and capture of the target CTCs, respectively. The AuIrPt nanozymes could approach the sensing interface and generate obvious currents through their exceptional catalytic activity only when all three proteins (MUC1, EpCAM, and EGFR) were simultaneously expressed on the cell membrane. Benefiting from the aforementioned advantages, our cytosensor could accurately distinguish between target cells and other cancer cells with a wide concentration range from 5 to 1 × 106 cells mL−1 and a low detection limit of 2 cells mL−1. Notably, the biosensor could assay target CTCs in complex whole blood matrixes, validating its resistance to interference and utility. By combining catalytic nanomaterials and three-site recognition strategy, a sensitive, accurate, and stable novel sensing platform has been developed, promising to facilitate the application of CTCs in early cancer screening.

Intelligent recognition of CTCs from gallbladder cancer by ultrasensitive electrochemical cytosensor and diagnosis of chemotherapeutic resistance

Gallbladder carcinoma (GBC) is one of most aggressive and lethal malignancies. Early diagnosis of GBC is crucial for determining appropriate treatment and improving chances of cure. Chemotherapy represents the main therapeutic regimen for unresectable GBC patients to inhibit tumor growth & metastasis. But, chemoresistance is the major cause of GBC recurrence. Thus, there is an urgent need to explore potentially non-invasive and point-of-care approaches to screen GBC and monitor their chemoresistance. Herein, we established an electrochemical cytosensor to specifically detect circulating tumor cells (CTCs) and their chemoresistance. Trilayer of CdSe/ZnS quantum dots (QDs) were cladded upon SiO2 nanoparticles (NPs), forming Tri-QDs/PEI@SiO2 electrochemical probes. Upon conjugation of anti-ENPP1, the electrochemical probes were able to specifically label captured CTCs from GBC. The detection of CTCs and chemoresistance were realized by square wave anodic stripping voltammetric (SWASV) responses to anodic stripping current of Cd 2+ ion when cadmium in electrochemical probes was dissolved and eventually electrodeposited on bismuth film-modified glassy carbon electrode (BFE). Taking use of this cytosensor, one ensured the screening of GBC and limit of detection for CTCs approaches to ～10 cells/mL. Furthermore, by monitoring phenotypic changes of CTCs after drug treatment, the diagnosis of chemoresistance was achieved by our cytosensor.

Multivalent aptamer nanoscaffold cytosensor for glioma circulating tumor cells during Epithelial–Mesenchymal transition

The key factor that causes glioma invasion and metastasis is circulating tumor cells (CTCs) undergoing epithelial–mesenchymal transition (EMT). Effective analysis of EMT-CTCs can provide an important foundation for early detection and prognosis monitoring of glioma, but the changes in the biomarkers of CTCs in different states of EMT make detection difficult. In this study, we developed a multivalent aptamer nanoscaffold-based electrochemical cytosensor (MAS-cytosensor) to efficiently detect EMT-CTCs. The two chains forming the MAS are composed of a specific aptamer detector, a binding region for DNA self-assembly, and a foothold for interface anchoring. When target CTCs exist, the bisaptamer detector on MAS can sensitively identify CTCs and pull them to the electrode surface, generating electrochemical signals. It has been demonstrated that the MAS-cytosensor can not only detect EMT-CTCs sensitively (detection limit of 6 cells/mL in buffer), but also allows for further downstream analysis after release with high viability. Overall, this cytosensor provides a reliable detection solution for CTCs regardless of their EMT status, and provides an efficient method for in-depth study role of the post-EMT CTCs in clinical application and metastasis mechanisms.

Hierarchal polyaniline-folic acid nanostructures act as a platform for electrochemical detection of tumor cells

The fabrication of electrochemical sensing platforms for cancer monitoring by quantifying circulating tumor cells (CTCs) in blood holds promise for providing a low-cost, rapid, feasible, and safe approach for cancer diagnosis. Here, we isolate cancer cells using CoFe2O4 nanoparticles functionalized with folic acid and chitosan as an inexpensive magnetic nanoprobe. This electrochemical cytosensing platform was realized using polyaniline-folic acid nanohybrids with a three-dimensional hierarchical structure that presents abundant affinity sites toward overexpressed folate bioreceptors on cancer cells, in addition to retaining satisfied conductivity. Furthermore, 3D modeling and simulation of the polyaniline-folic acid structures were conducted to investigate the stable complex between aniline and folate, and the interaction between the polyaniline-folate complex and folate receptor alpha1, a bioreceptor on MCF-7 was revealed for the first time. The limit of detection was calculated to be 4 cells mL−1 with a linear range from 50 to 106 cells mL−1.

A Proof-of-Concept Electrochemical Cytosensor Based on Chlamydomonas reinhardtii Functionalized Carbon Black Screen-Printed Electrodes: Detection of Escherichia coli in Wastewater as a Case Study.

Herein, we report a proof-of-concept algal cytosensor for the electrochemical quantification of bacteria in wastewater, exploiting the green photosynthetic alga Chlamydomonas reinhardtii immobilized on carbon black (CB) nanomodified screen-printed electrodes. The CB nanoparticles are used as nanomodifiers, as they are able to sense the oxygen produced by the algae and thus the current increases when algae are exposed to increasing concentrations of bacteria. The sensor was tested on both standard solutions and real wastewater samples for the detection Escherichia coli in a linear range of response from 100 to 2000 CFU/100 mL, showing a limit of detection of 92 CFU/100 mL, in agreement with the maximum E. coli concentration established by the Italian law for wastewater (less than 5000 CFU/100 mL). This bacterium was exploited as a case study target of the algal cytosensor to demonstrate its ability as an early warning analytical system to signal heavy loads of pathogens in waters leaving the wastewater treatment plants. Indeed, the cytosensor is not selective towards E. coli but it is capable of sensing all the bacteria that induce the algae oxygen evolution by exploiting the effect of their interaction. Other known toxicants, commonly present in wastewater, were also analyzed to test the cytosensor selectivity, with any significant effect, apart from atrazine, which is a specific target of the D1 protein of the Chlamydomonas photosystem II. However, the latter can also be detected by chlorophyll fluorescence simultaneously to the amperometric measurements. The matrix effect was evaluated, and the recovery values were calculated as 105 ± 8, 83 ± 7, and 88 ± 7% for 1000 CFU/100 mL of E. coli in Lignano, San Giorgio, and Pescara wastewater samples, respectively.

DNA walker induced “signal off” electrochemical cytosensor strategy for ultrasensitive detection of tumor cells

The fragments of molecular motors can be transported and operated autonomously along a track. Most molecular walker systems are assembled from DNA building modules, exhibiting great potential applications in biocomputing, drug transport, sensing, etc. Hereby, we report a DNA walker driven by endonuclease Nt.BbvC I that can autonomously induce “signal off” sensing platform for highly sensitive detection of tumor cells. DNA density and trajectory conformation can affect DNA walker properties. Molybdenum selenide@gold nanoparticles (MoSe2@AuNPs) are modified on the electrode surface as a scaffold to accommodate more hairpin probe (H1) and provide a good interface for DNA walking. Magnetic beads are used to enrich target tumor cells, release single-stranded DNA (S1) and trigger DNA walker-based amplification strategy. Upon addition of tumor cells, more DNA-methylene blue (DNA-MB) is cracked from the electrode surface. Benefiting from efficient electrode modification, magnetic enrichment, DNA walker and enzyme-assisted amplification, an ultra-high sensitivity electrochemical cell analysis is realized, with a detection limit of 2 cells mL−1. More importantly, this DNA walker strategy is available for tumor cell analysis in clinical samples, suggesting the potential diagnostic applications.

Platinum-Based Nanocomposite Pt@BSA as an Efficient Electrochemical Biosensing Interface for Rapid and Ultrasensitive Determination of Folate Receptor-Positive Tumor Cells.

Developing a cytosensing strategy based on electrochemical approaches has attracted wide interest due to the low cost, rapid response, and simple instrumentation. In this work, an electrochemical cytosensor employing the Pt@BSA nanocomposite as the biosensing substrate along with the covalent cross-linking of targeting molecules folic acid (FA) was constructed for highly sensitive determination of folate receptor (FR)-positive tumor cells. The prepared Pt@BSA nanocomposite revealed excellent biocompatibility for cell adhesion and proliferation, which was confirmed by cell viability evaluation using thiazolyl blue tetrazolium bromide (MTT) colorimetric methods. Due to the satisfactory electrical conductivity originating from Pt@BSA and the high binding affinity of FA to FR on the cell surface, an ultrasensitive and specific cytosensing device was designed for rapid and quantitative determination of HeLa cells (a model system) by differential pulse voltammetry (DPV) tests. This proposed cytosensor resulted in a wide HeLa cell determination range of 2.8 × 101-2.8 × 106 cells mL-1 with a low DPV detection limit of 9 cells mL-1. The developed cytosensing approach exhibited highly specific recognition of FR-positive tumor cells, excellent inter-assay reproducibility with a relative standard deviation (RSD) of 4.7%, acceptable intra-assay precision, and favorable storage stability, expanding the application of electrochemical measurement technology in the biomedical field of early detection and diagnosis of cancers.

Design of a nanocytosensor for isolation and electrochemical detection of folate-overexpressed circulating tumor cells

Magnetic nanomaterial-based electrochemical cytosensor holds great promise to tackle the challenges in isolation and detection of circulating tumor cells (CTCs) by the combination of the selectivity of magnetic cell separation with high sensitivity of electrochemical sensing platforms. Herein, by leveraging nanomaterials with L-cysteine and folic acid, we design innovative biomaterials for electrochemical cell detection, with minimal materials and materials manufacturing steps. Folic acid-L-cysteine-capped CoFe2O4 nanoparticles (CCF) are developed to magnetically capture folate-overexpressed tumor cells. Hybrids of L-cysteine-folic acid and silver nanowires (FAgNWs) are synthesized using a green, convenient and template-free approach without any surfactant. Direct immobilization of L-cysteine and folic into silver nanowires hybrids facilitates the electrode preparation and cell detection. The density functional theory and molecular dynamics simulations were also used to provide deep insight into the interaction of silver nanowires with L-cysteine coupled with folic acid (LCFA). An affordable nanocytosensor is proposed for the detection of CTCs by sandwiching the MCF-7 cells captured between CCF and FAgNWs. This nanocytosensor has the low detection limit of 5 MCF-7 cells/mL with the wide dynamic range of 50–106 cells/mL. The presented nanomaterial-based sensing platform is promising for convenient cell isolation and detection.

A c-MWCNTs/AuNPs-based electrochemical cytosensor to evaluate the anticancer activity of pinoresinol from Cinnamomum camphora against HeLa cells

A sensitive, simple, label-free electrochemical cytosensor was developed to evaluate the anticancer activity of pinoresinol against human cervical carcinoma (HeLa) cells. HeLa cells were immobilised on carboxylated multi-walled carbon nanotubes (c-MWCNTs)/gold nanoparticles (AuNPs) nanocomposite-modified glassy carbon electrodes. Scanning electron microscopy, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray diffractometry were used to characterise the morphology, crystallinity, and composition of the nanocomposites. Cyclic voltammetry was used to characterise and optimise the cytosensor. Both c-MWCNTs and AuNPs increased the electron-transfer rate between the HeLa cells and the electrode, retaining good cell compatibility. The concentration of HeLa cells immobilised on the nanocomposite electrode exhibited a good correlation with the impedance values determined by electrochemical impedance spectroscopy in the range of 102–106 cells/mL (detection limit of 102 cells/mL) with R2 = 0.975. HeLa cells were then immobilised on the nanocomposite electrode at a concentration of 104 cells/mL, and it was used as a cytosensor. The anticancer activity of pinoresinol from Cinnamomum camphora was evaluated by determining the median inhibitory concentration using the proposed cytosensor. For comparison, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and fluorescent imaging were simultaneously performed, which confirmed the results of the cytosensor. The cytosensor is promising for future applications in anticancer drug screening.

Electrochemical Cytosensor Based on a Gold Nanostar-Decorated Graphene Oxide Platform for Gastric Cancer Cell Detection.

Effectively capturing and sensitively detecting cancer cells are critical to clinical diagnosis and cancer therapy. In this work, we prepared gold nanostar-decorated graphene oxide (GO-AuNSs) nanocomposites using a ultraviolet (UV)-induced strategy, and then modified them with a layer of bio-complex rBSA-FA (coupled reduced bovine serum albumin with folic acid) to generate GO-AuNSs@rBSA-FA nanocomposites. Herein, the application of GO and AuNSs not only strengthened the conductivity of the sensing platform but also guaranteed nanocomposites with biocompatible performance. Moreover, the adopted rBSA-FA layer could effectively enhance the stability and specificity towards gastric cancer cells (MGC-803). According to a systemic construction procedure, a novel electrochemical cytosensor based on GO-AuNSs@rBSA-FA was fabricated for MGC-803 cell detection. With the assistance of cyclic voltammetry (CV) and differential pulse voltammetry (DPV), the cytosensor reached a detection limit of 100 cell/mL in a wide linear range of 3 × 102~7 × 106 cell/mL towards MGC-803 cells. The good electrochemical characteristics for the cancer cell analysis indicate a promising prospect of this electrochemical cytosensor in clinical cancer diagnosis.

A highly sensitive electrochemical cytosensor based on a triple signal amplification strategy using both nanozyme and DNAzyme.

The development of a sensitive cytosensor is beneficial for the early diagnosis and treatment of cancer. Herein, highly sensitive cytosensing was achieved by applying triple signal amplification strategies with Fe3O4@Au nanozymes and DNAzyme hybrids as electrochemical nanoprobes and toluidine blue (Tb) as the electron transfer medium. The Fe3O4@Au nanocomposites not only acted as nanozymes with excellent catalytic performance towards H2O2 reduction but also served as promising scaffolds to carry massive electroactive substances and DNA probes. The dual-functional DNA probes were designed with the sequence of hemin/G-quadruplex to serve as the DNAzyme and the sequence of aptamer to recognize cancer cells. Furthermore, Tb was also conjugated to the surface of the Fe3O4@Au nanohybrids, working as the electron transport medium to magnify the electrochemical response. With the above design, the Fe3O4@Au nanozymes and hemin/G-quadruplex DNAzyme efficiently co-catalyzed the reduction of H2O2 to accelerate the electron transfer of Tb, which realized triple signal amplification and finally improved the performance of the electrochemical cytosensor. The proposed cytosensor achieved a sensitive detection of HepG2 cells with a low detection limit of 20 cells mL-1, and could be potentially used as an effective analysis tool in early cancer diagnosis in the future.

DNA Walker Induced “Signal Off” Electrochemical Cytosensor Strategy for Ultrasensitive Detection of Tumor Cells

DNA Walker Induced “Signal Off” Electrochemical Cytosensor Strategy for Ultrasensitive Detection of Tumor Cells

Multifunctional Gold Nano-Cytosensor With Quick Capture, Electrochemical Detection, and Non-Invasive Release of Circulating Tumor Cells for Early Cancer Treatment.

Circulating tumor cells (CTCs) are metastatic tumor cells that shed into the blood from solid primary tumors, and their existence significantly increases the risk of metastasis and recurrence. The timely discovery and detection of CTCs are of considerable importance for the early diagnosis and treatment of metastasis. However, the low number of CTCs hinders their detection. In the present study, an ultrasensitive electrochemical cytosensor for specific capture, quantitative detection, and noninvasive release of EpCAM-positive tumor cells was developed. The biosensor was manufactured using gold nanoparticles (AuNPs) to modify the electrode. Three types of AuNPs with controllable sizes and conjugated with a targeting molecule of monoclonal anti-EpCAM antibody were used in this study. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) of the cytosensors were performed to evaluate the cell capture efficiency and performance. The captured 4T1 cells by the AuNPs hindered electron transport efficiency, resulting in increased EIS responses. The cell capture response recorded using EIS or DPV indicated that the optimal AuNPs size should be 17 nm. The cell capture response changed linearly with the concentration range from 8.0 × 10 to 1 × 107 cells/mL, and the limit of detection was 50 cells/mL. After these measurements, glycine-HCl (Gly-HCl) was used as an antibody eluent to destroy the binding between antigen and antibody to release the captured tumor cells without compromising their viability for further clinical research. This protocol realizes rapid detection of CTCs with good stability, acceptable assay precision, significant fabrication reproducibility with a relative standard deviation of 2.09%, and good recovery of cells. Our results indicate that the proposed biosensor is promising for the early monitoring of CTCs and may help customize personalized treatment options.

Electrochemical Sensors for Detection of Markers on Tumor Cells.

In recent years, the increasing incidence and mortality of cancer have inspired the development of accurate and rapid early diagnosis methods in order to successfully cure cancer; however, conventional methods used for detecting tumor cells, including histopathological and immunological methods, often involve complex operation processes, high analytical costs, and high false positive rates, in addition to requiring experienced personnel. With the rapid emergence of sensing techniques, electrochemical cytosensors have attracted wide attention in the field of tumor cell detection because of their advantages, such as their high sensitivity, simple equipment, and low cost. These cytosensors are not only able to differentiate tumor cells from normal cells, but can also allow targeted protein detection of tumor cells. In this review, the research achievements of various electrochemical cytosensors for tumor cell detection reported in the past five years are reviewed, including the structures, detection ranges, and detection limits of the cytosensors. Certain trends and prospects related to the electrochemical cytosensors are also discussed.

An Efficient Graphene Quantum Dots-Based Electrochemical Cytosensor for the Sensitive Recognition of CD123 in Acute Myeloid Leukemia Cells

Leukemia stem cells (LSCs) are suitable candidates to be deployed for the diagnosis and therapy of acute myeloid leukemia (AML) patients. In this study, a novel electrochemical cytosensor was designed for the sensitive detection and quantification of KG1a cells as a model of LSCs. The developed cytosensor was based on the overexpression of cell surface protein CD123 by leukemia KG1a cells. For this purpose, the glassy carbon electrode was modified by graphene quantum dots (GQDs), Au nanoparticles, streptavidin coated AuNPs, biotinylated CD123 antibody and target cells. The dense loading of CD123 antibody and electrical enhancement on the modified electrode were carried out using GQDs, this resulting in a sensitive detection of CD123 positive cells within KG1a cells. Step by step preparation of the nanomaterial-based cytosensor and its optimization steps were confirmed by different electrochemical techniques. The field emission scanning electron microscopy (FE-SEM) images also confirmed the proper attachment of the materials and the cells on the surface of the modified electrode. The linear detection range (LDR) and limit of detection (LOD) of the developed electrochemical biosensor were recorded as 1 cell/mL and 1-25 cells/mL, respectively, which is remarkable. Importantly, the present findings are precise and highly selective in the presence of other leukemia cells (NB4, HL60, and U937 cells). Further, the versatility and accuracy of the proposed cytosensor were evaluated using clinical samples. We believe that the cytosensor proposed in this study has the potential to serve as a next generation sensor for the early detection of leukemia stem cells.

Cell-based electrochemical cytosensor for rapid and sensitive evaluation of the anticancer effects of saponin on human malignant melanoma cells

Discovering new anticancer agents and analyzing their activities is a vital part of drug development, but it requires a huge amount of time and resources, leading to the increasing demands for more-effective techniques. Herein, a novel and simple cell-based electrochemical biosensor, referred to as a cytosensor, was proposed to investigate the electrochemical behavior of human skin malignant melanoma (SK-MEL28) cells and the anticancer effect of saponin on cell viability. To enhance both electrocatalytic properties and biocompatibility, gold nanoparticles were electrochemically deposited onto a conductive substrate, and poly-L-lysine was further added to the electrode surface. Electric signals from SK-MEL28 cells on the electrodes were obtained from cyclic voltammetry and differential pulse voltammetry. The cathodic peak current was proportional to the cell viability and showed a detection range of 2,880–40,000 cells per device with an excellent linear cell number-intensity relationship (R2= 0.9952). Furthermore, the anticancer effect of saponin on SK-MEL28 cells was clearly established at concentrations higher than 20 μM, which was highly consistent with conventional assays. Moreover, the developed electrochemical cytosensor for evaluating anticancer effects enabled rapid (<2 min), sensitive (LOQ: 2,880cells/device), and non-invasive measurements, thus providing a new avenue for assessing the anticancer drugs in vitro.

Electrochemical detection of circulating tumor cells: A mini review

Circulating tumor cell (CTC) is an important biomarker for early diagnosis of cancer. Among a number of greatly advanced strategies, electrochemical CTC sensors show advantages such as simplicity, fast response, low cost and the capability for miniaturization. In this mini review, we present recent development of the electrochemical cytosensors primarily in the past 5 years based on different detection principles. In the conclusion, we point out the current challenges of the electrochemical CTC detection platform and highlight the importance of single CTC detection. An outlook particularly on the impact method for single CTC analysis is also given.