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.

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Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Micromachines ◽

10.3390/mi11080774 ◽

2020 ◽

Vol 11 (8) ◽

pp. 774 ◽

Cited By ~ 2

Author(s):

Jie Cheng ◽

Yang Liu ◽

Yang Zhao ◽

Lina Zhang ◽

Lingqian Zhang ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Liquid Biopsy ◽

Cancer Metastasis ◽

Human Peripheral Blood ◽

Microfluidic Devices ◽

Detection Sensitivity ◽

Cell Capture ◽

Primary Tumors ◽

Downstream Analysis

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

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A highly sensitive octopus-like azobenzene fluorescent probe for determination of abamectin B1 in apples

Scientific Reports ◽

10.1038/s41598-021-84221-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhenlong Guo ◽

YiFei Su ◽

Kexin Li ◽

MengYi Tang ◽

Qiang Li ◽

...

Keyword(s):

Fluorescent Probe ◽

Limit Of Detection ◽

Quantitative Detection ◽

Fluorescence Signal ◽

Ionization Mass ◽

Limit Of Quantification ◽

Visible Absorption ◽

Esi Ms ◽

Relative Standard ◽

Ft Ir

AbstractThe development of detecting residual level of abamectin B1 in apples is of great importance to public health. Herein, we synthesized a octopus-like azobenzene fluorescent probe 1,3,5-tris (5′-[(E)-(p-phenoxyazo) diazenyl)] benzene-1,3-dicarboxylic acid) benzene (TPB) for preliminary detection of abamectin B1 in apples. The TPB molecule has been characterized by ultraviolet–visible absorption spectrometry, 1H-nuclear magnetic resonance, fourier-transform infrared (FT-IR), electrospray ionization mass spectroscopy (ESI-MS) and fluorescent spectra. A proper determination condition was optimized, with limit of detection and limit of quantification of 1.3 µg L−1 and 4.4 μg L−1, respectively. The mechanism of this probe to identify abamectin B1 was illustrated in terms of undergoing aromatic nucleophilic substitution, by comparing fluorescence changes, FT-IR and ESI-MS. Furthermore, a facile quantitative detection of the residual abamectin B1 in apples was achieved. Good reproducibility was present based on relative standard deviation of 2.2%. Six carboxyl recognition sites, three azo groups and unique fluorescence signal towards abamectin B1 of this fluorescent probe demonstrated reasonable sensitivity, specificity and selectivity. The results indicate that the octopus-like azobenzene fluorescent probe can be expected to be reliable for evaluating abamectin B1 in agricultural foods.

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Isolation of ovarian cancer circulating tumor cells using an epitope independent microfluidic cell capture device and their interrogation using a multiplex gene expression assay or immunofluorescence

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.06.051 ◽

2020 ◽

Vol 159 ◽

pp. 24

Author(s):

N. Khazan ◽

K. Kim ◽

A. Hustler ◽

A.S. Pailhes-Jimenez ◽

M. Ciccioli ◽

...

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cell Capture ◽

Gene Expression Assay

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Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer

Journal of Oncology ◽

10.1155/2010/617421 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 379

Author(s):

M. Craig Miller ◽

Gerald V. Doyle ◽

Leon W. M. M. Terstappen

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Treatment Options ◽

Venous Blood ◽

Metastatic Breast ◽

Cellsearch System ◽

Multicenter Studies ◽

Real Time Analysis ◽

Number Of Treatment

The increasing number of treatment options for patients with metastatic carcinomas has created a concomitant need for new methods to monitor their use. Ideally, these modalities would be noninvasive, be independent of treatment, and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells (CTCs) shed into the blood during metastasis may satisfy this need. We developed the CellSearch System to enumerate CTC from 7.5 mL of venous blood. In this review we compare the outcomes from three prospective multicenter studies investigating the use of CTC to monitor patients undergoing treatment for metastatic breast (MBC), colorectal (MCRC), or prostate cancer (MPC) and review the CTC definition used in these studies. Evaluation of CTC at anytime during the course of disease allows assessment of patient prognosis and is predictive of overall survival.

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Cancer Diagnostics: Visual Quantitative Detection of Circulating Tumor Cells with Single‐Cell Sensitivity Using a Portable Microfluidic Device (Small 14/2019)

Small ◽

10.1002/smll.201970075 ◽

2019 ◽

Vol 15 (14) ◽

pp. 1970075

Author(s):

Mahlet Fasil Abate ◽

Shasha Jia ◽

Metages Gashaw Ahmed ◽

Xingrui Li ◽

Li Lin ◽

...

Keyword(s):

Single Cell ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Microfluidic Device ◽

Cancer Diagnostics ◽

Quantitative Detection ◽

Cell Sensitivity

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Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽

10.3390/diagnostics10040192 ◽

2020 ◽

Vol 10 (4) ◽

pp. 192

Author(s):

Leonie Konczalla ◽

Anna Wöstemeier ◽

Marius Kemper ◽

Karl-Frederik Karstens ◽

Jakob Izbicki ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Application ◽

Liquid Biopsy ◽

Cancer Diagnostics ◽

Therapeutic Approaches ◽

Primary Tumors ◽

New Therapeutic Approaches ◽

Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

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