•A label-free and ultrasensitive EIS cytosensor was developed to detect CTCs.•The viable HepG-2 cells were captured to the senor by a multivalent Gal-ASGP-R binding.•The nanostructured GNI has an enhanced electro-transfer rate and a low LOD of 30 cell mL− 1.•The EIS biosensor has a good reproducibility with the RSD of 1.9% in blood samples.•It provides a versatile and noninvasive sensing platform for early diagnosis of tumor.Circulating tumor cells (CTCs), as potential cancer biomarkers, play a crucial role in cancer diagnosis, prognosis and treatment. However, there are still significant challenges due to their rarity. In this paper, a label-free and ultrasensitive electrochemical impedance cytosensor was developed by a galactosylated gold-nanoisland (Gal-GNI) biointerface for the capture and detection of rare cancer cells (HepG-2) in whole blood samples. By mimic the natural multivalent biorecognition systems, the biointerface was designed to capture the target cancer cells by the specific binding between galactosyl ligands of Gal-GNI and over-expressed asialoglycoprotein receptors (ASGP-R) on the surface of HepG-2. From the results of electrochemical impedance spectroscopy (EIS) and fluorescence spectroscopy, the nanostructured Gal-GNI provides an improved electron-transfer rate, specific detection for HepG-2, and good biocompatibility for viable captured cells. The capture of HepG-2 to the EIS cytosensor increased the electron-transfer resistance, with a good correlation with the logarithm of the concentration from 1.0 × 102 to 1.0 × 105 cells mL− 1, with a low detection limit of 30 cells mL− 1. This cytosensing strategy has good reproducibility with the RSD of 1.9% in blood samples, indicating that it can be used as a potential noninvasive assay tool for the early diagnosis and therapy of tumor.

Rapid and efficient detection of cancer cells at their earliest stages is one of the central challenges in cancer diagnostics. We developed a simple, cost-effective, and highly sensitive colorimetric method for visually detecting rare cancer cells based on cell-triggered cyclic enzymatic signal amplification (CTCESA). In the absence of target cells, hairpin aptamer probes (HAPs) and linker DNAs stably coexist in solution, and the linker DNA assembles DNA-AuNPs, producing a purple solution. In the presence of target cells, the specific binding of HAPs to the target cells triggers a conformational switch that results in linker DNA hybridization and cleavage by nicking endonuclease-strand scission cycles. Consequently, the cleaved fragments of linker DNA can no longer assemble into DNA-AuNPs, resulting in a red color. UV–vis spectrometry and photograph analyses demonstrated that this CTCESA-based method exhibited selective and sensitive colorimetric responses to the presence of target CCRF-CEM cells, which could be detected by the naked eye. The linear response for CCRF-CEM cells in a concentration range from 102 to 104 cells was obtained with a detection limit of 40 cells, which is approximately 20 times lower than the detection limit of normal AuNP-based methods without amplification. Given the high specificity and sensitivity of CTCESA, this colorimetric method provides a sensitive, label-free, and cost-effective approach for early cancer diagnosis and point-to-care applications.

Rapid and efficient measurement of cancer cells is a major challenge in early cancer diagnosis. In the present study, a miniature multiplex chip was created for in situ detection of cancer cells by implementing a novel graphene oxide (GO)-based Förster resonance energy transfer (FRET) biosensor strategy, i.e. assaying the cell-induced fluorescence recovery from the dye-labeled aptamer/graphene oxide complex. Fluorescence intensity measurement and image analyses demonstrated that this microfluidic biosensing method exhibited rapid, selective and sensitive fluorescence responses to the quantities of the target cancer cells, CCRF-CEM cells. Seven different cancer cell samples can be measured at the same time in such a microfluidic chip. The linear response for target CCRF-CEM cells in a concentration range from 2.5 × 101 to 2.5 × 104 cells mL−1 was obtained, with a detection limit about 25 cells mL−1, which is about ten times lower than those of normal biosensors. The novel fluorescence biosensing microfluidic chip supplies a rapid, visible and high-throughput approach for early cancer diagnosis with high sensitivity and specificity.

A sensitive and reagentless electrochemical aptamer-based (E-AB) sensor for specific recognition of thrombin was developed based on the Fe3O4-nanoparticle(FNP)-tagged technique. The FNP-tagged aptasensor was fabricated with a bifunctional aptamer covalently linked by a FNP tag at 3′-terminus and self-assembled on the gold electrode at 5′-terminus, which were characterized by TEM, AFM, UV–Vis and electrochemical impedance spectra. Specific binding of thrombin with the aptamer on this aptasensor produced a redox signal and detected by differential pulse voltammetry, where FNP-tag could gain signal-amplification due to its containing more redox centers. The aptasensor showed a linear response for thrombin in the range of 1.0–75 nM, and a lower detection limit of 0.1 nM (at S/N = 3). The E-AB sensor was high sensitive and stable, and could be used to detect target protein at a clinic level in biological samples.Research highlights► A reagentless aptasensor for specific recognition of thrombin was developed. ► Specific binding of thrombin with the aptamer on this aptasensor produced a redox signal. ► The Fe3O4-nanoparticle tag is sensitive and can gain signal-amplification. ► A detection limit of 0.1 nM for thrombin with desirable specificity, stability and sensitivity. ► The aptasensor can selectively detect the target protein in complex samples.

A sensitive molecularly imprinted electrochemical sensor was created for selective detection of a tricyclic antidepressant imipramine by combination of Au nanoparticles (Au-NPs) with a thin molecularly imprinted film. The sensor was fabricated onto the indium tin oxide (ITO) electrode via stepwise modification of Au-NPs by self-assembly and a thin film of molecularly imprinted polymers (MIPs) via sol–gel technology. It was observed that the molecularly imprinted film displayed excellent selectivity towards the target molecule imipramine. Meanwhile, the introduced Au-NPs exhibited noticeable catalytic activities towards imipramine oxidation, which remarkably enhanced the sensitivity of the imprinted film. Due to such combination, the as-prepared sensor responded quickly to imipramine, within only 1 min of incubation. The differential voltammetric anodic peak current was linear to the logarithm of imipramine concentration in the range from 5.0 × 10−6 to 1.0 × 10−3 mol L−1, and the detection limits obtained was 1.0 × 10−9 mol L−1. This method proposed was successfully applied to the determination of imipramine in drug tablets, and proven to be reliable compared with conventional UV method. These results reveal that such a sensor fulfills the selectivity, sensitivity, speed and simplicity requirements for imipramine detection, and provides possibilities of clinical application in physiological fluids.

A sensitive and label-free electrochemical impedance immunosensor via covalent coupling the antibody with functionalized gold nanoparticles (FAuNP) for probing apolipoprotein A-I was presented. The hybrid gold nanoparticles were prepared with a two-in-one strategy, i.e. via the stepwise employment of self-assembled monolayer (SAM) and sol–gel techniques, to improve the performance of such a label-free immunosensor, which was investigated by electrochemical impedance spectroscopy. It was found that this novel FAuNP immunosensor showed higher protein-loading capacity and better response properties (6–17 times) than that fabricated by normal SAM technique did. The remarkably improved properties of the immunosensor were ascribed to FAuNP with the larger surface-to-volume ratio, more free amino linkage groups, and the lower nonspecific protein adsorption. As a result, the thus-prepared antibody-modified immunosensor showed reproducible (R.S.D. = ±3.2%, n = 10) linear response to apolipoprotein A-I (Apo A-I) antigens in the range of 0.1–10 ng mL−1. The detection limit of this immunosensor was 50 pg mL−1 (corresponding to 1.8 pmol L−1), which was two orders of magnitude lower than that of the traditional methods. These results exhibited the novel immunosensor had a high sensitivity, stability and selectivity for the determination of Apo A-I, especially in clinic microanalysis.

•A label-free GO-based aptasensor for detecting low quantity cancer cells based on CTCESA.•A good amplification efficiency and specificity of CTCESA makes a low LOD of 25 cells.•This homogeneous cell-assay method is simple, avoiding cell-immobilization and washing.•The method provides a generic approach with a specific HAP for early cancer diagnosis.A label-free and high-efficient graphene oxide (GO)-based aptasensor was developed for the detection of low quantity cancer cells based on cell-triggered cyclic enzymatic signal amplification (CTCESA). In the absence of target cells, hairpin aptamer probes (HAPs) and dye-labeled linker DNAs stably coexisted in solution, and the fluorescence was quenched by the GO-based FÖrster resonance energy transfer (FRET) process. In the presence of target cells, the specific binding of HAPs with the target cells triggered a conformational alternation, which resulted in linker DNA complementary pairing and cleavage by nicking endonuclease-strand scission cycles. Consequently, more cleaved fragments of linker DNAs with more the terminal labeled dyes could show the enhanced fluorescence because these cleaved DNA fragments hardly combine with GOs and prevent the FRET process. Fluorescence analysis demonstrated that this GO-based aptasensor exhibited selective and sensitive response to the presence of target CCRF-CEM cells in the concentration range from 50 to 105 cells. The detection limit of this method was 25 cells, which was approximately 20 times lower than the detection limit of normal fluorescence aptasensors without amplification. With high sensitivity and specificity, it provided a simple and cost-effective approach for early cancer diagnosis.