Search

Tumor cells in blood circulation (CTCs) are vital biomarkers for noninvasive cancer diagnosis. We developed a simple and sensitive electrochemical biosensor based on dual-toehold accelerated catalytic hairpin assembly (DCHA) to distinguish CTCs from blood cells. In the presence of CTCs, the aptamer probe initiates the DCHA process, which produces amplified electrochemical signals. Compared with conventional catalytic hairpin assembly (CHA), the proposed DCHA showed high sensitivity, which led to a broader working range of 10-1000 cells mL -1 with a limit of detection of 4 cells mL -1 . Furthermore, our method exhibited an excellent capability of distinguishing malignant breast cancers from healthy people, with a sensitivity of 97.4%. In summary, we have established an enzyme-free, easy-to-operate, and nondisruptive method for detecting circulating tumor cells in blood circulation based on the DCHA strategy. Its versatility and simplicity will make it more widely used in clinical diagnosis and biomedical research., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Surface protein patterns of tumor-derived exosomes could be promising noninvasive diagnostic biomarkers for liquid biopsy. However, a convenient and cost-effective platform for exosomal protein profiling is still lacking. Herein, a facile fluorescent aptasensor is developed to assess exosomal tumor-associated proteins, combining aptamers, aggregation-induced emission luminogens (AIEgens), and graphene oxide (GO) as recognition elements, fluorescent dye, and the quencher, respectively. Specifically, numberous TPE-TAs could bind one aptamer and form aggregates rapidly, resulting in an amplified fluorescence signal. In the absence of tumor-derived exosomes, GO absorbs the TPE-TAs/aptamer complex, allowing fluorescence quenching. When the target exosomes are introduced, the aptamer preferentially binds with its target. Thus the TPE-TAs/aptamer complexes detach from GO surface, followed by the appearance of a "turn-on" fluorescent signal. Under the optimized conditions, the linear range of target exosomes is estimated to be 4.07 × 10 5 to 1.83 × 10 7 particles/μL (0.68-30.4 pM) with a detection limit of 3.43 × 10 5 particles/μL (0.57 pM). This strategy demonstrated great performance in differentiating prostate cancer from healthy individuals (AUC: 0.9790). Furthermore, by profiling three tumor-associated protein markers including epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), and human epidermal growth factor receptor 2 (HER2) on exosomes in a breast tumor cohort, this sensing platform diagnoses breast tumors with high efficiency (AUC: 0.9845) and exhibits a high sensitivity of 97.37% for distinguishing malignant breast cancers, where the stage I cases were detected with 92.31% sensitivity. Therefore, this aptasensor provides a promising strategy to profile tumor-derived exosomal proteins for early diagnosis in liquid biopsy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The presence of cancer cells in body fluids confirms the occurrence of metastasis and guides treatment. A simple, fast, and homogeneous fluorescent method was developed to detect cancer cells based on catalytic hairpin assembly (CHA) and bifunctional aptamers. The bifunctional aptamer had a recognition domain for binding to target cancer cells and an initiator domain for triggering the CHA reaction. In the presence of target cells, the bifunctional aptamer was released from the inhibitor and initiated a cascade reaction of assembly and disassembly of the hairpins. Separation of the fluorophores from the quenchers produced fluorescence signals. The proposed strategy showed high specificity for discriminating normal cells and leukocytes, and the detection limit was 10 cells/mL, which was lower than that of previous aptasensors. This assay was further tested using four kinds of clinical samples spiked with target cells to confirm its applicability. We developed a simple, rapid, and cost-effective method for the detection of cancer cells that did not require purification, and the approach holds great potential for bioanalysis and early diagnosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rare cancer cells in body fluid could be useful biomarkers for noninvasive diagnosis of cancer. However, detection of these rare cells is currently challenging. In this work, a binding-induced dual catalytic hairpin assembly (DCHA) electrochemical cytosensor was developed for highly selective and sensitive detection of cancer cells. The fuel probe, released by hybridization between the capture probe and catalytic hairpin assembly (CHA) products of target cell-responsive reaction, initiated dual CHA recycling, leading to multiple CHA products. Furthermore, the hybridization between fuel probe and capture probe decreased non-specific CHA products, improving the signal-to-noise ratio and detection sensitivity. Under the optimal conditions, the developed cytosensor was able to detect cells down to 30 cells mL -1 (S/N = 3) with a linear range from 50 to 100,000 cells mL -1 and was capable of distinguishing target cells from normal cells in clinical blood samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)