Detection of circulating tumor cells based on improved SERS-active magnetic nanoparticles

2019 ◽  
Vol 11 (22) ◽  
pp. 2918-2928 ◽  
Author(s):  
Ting Xue ◽  
Siqi Wang ◽  
Guoyu Ou ◽  
Yong Li ◽  
Huimin Ruan ◽  
...  

A SERS-active magnetic nanoparticle was developed for capture, enrichment and detection of cancer cells from blood samples. The isolated CTCs can also be released for further cell expansion, phenotype identification and molecular analysis.

Nano LIFE ◽  
2020 ◽  
Vol 10 (03) ◽  
pp. 1971001 ◽  
Author(s):  
Shengming Wu ◽  
Yilong Wang ◽  
Donglu Shi

Isolation of circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and metastasis diagnosis. Although many new detection methods have emerged in recent years, the detection of CTCs is a current challenge due to lack of specific and sensitive markers. In our previous work, cancer cell surfaces, from over 20 cancer cell lines, have been shown to be negatively-charged regardless of their phenotype by using electrically-charged nanoparticles as a probe. The strong electrostatic interaction between the negative cancer cells and positively charged nanoparticles can well remain in a physiological liquid environment in the presence of serum proteins, enabling effective binding between them. As a result, the cancer cells can be magnetically separated by employing an external magnet. In this technical report, we present preliminary results on the investigation of CTC isolation from both mimetic and clinical blood samples. We show high CTC detection sensitivity by the positively-charged magnetic nanoparticles (PMNs) even at the original concentration of 10 cells per mL mimetic blood sample. The CTCs in the peripheral blood of colorectal cancer patients were isolated and identified by cellular morphology and immunofluorescence staining.


2020 ◽  
Vol 21 (7) ◽  
pp. 2401 ◽  
Author(s):  
Nicolai T. Sand ◽  
Tobias B. Petersen ◽  
Sara R. Bang-Christensen ◽  
Theresa D. Ahrens ◽  
Caroline Løppke ◽  
...  

Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.


2020 ◽  
Vol 10 (9) ◽  
pp. 3338 ◽  
Author(s):  
David Lynch ◽  
Branka Powter ◽  
Joseph William Po ◽  
Adam Cooper ◽  
Celine Garrett ◽  
...  

Glioblastoma (GBM) is the most common form of primary brain cancer in adults and tissue biopsies for diagnostic purposes are often inaccessible. The postulated idea that brain cancer cells cannot pass the blood–brain barrier to form circulating tumor cells (CTCs) has recently been overthrown and CTCs have been detected in the blood of GBM patients albeit in low numbers. Given the potential of CTCs to be analyzed for GBM biomarkers that may guide therapy decisions it is important to define methods to better isolate these cells. Here, we determined markers for immunomagnetic targeting and isolation of GBM-CTCs and confirmed their utility for CTC isolation from GBM patient blood samples. Further, we identified a new marker to distinguish isolated GBM-CTCs from residual lymphocytes.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Zongbin Liu ◽  
Yuqing Huang ◽  
Wenli Liang ◽  
Jing Bai ◽  
Hongtao Feng ◽  
...  

Precise isolation and analysis of circulating tumor cells (CTCs) from blood samples offer considerable potential for cancer research and personalized treatment. Currently, available CTCs isolation approaches remain challenging in the...


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1119
Author(s):  
Ivonne Nel ◽  
Erik W. Morawetz ◽  
Dimitrij Tschodu ◽  
Josef A. Käs ◽  
Bahriye Aktas

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.


2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.


2018 ◽  
Vol 20 (1) ◽  
pp. 329-352 ◽  
Author(s):  
Eric Lin ◽  
Thong Cao ◽  
Sunitha Nagrath ◽  
Michael R. King

Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.


Nanoscale ◽  
2015 ◽  
Vol 7 (39) ◽  
pp. 16470-16480 ◽  
Author(s):  
Hyun-Chul Kim ◽  
Eunjoo Kim ◽  
Sang Won Jeong ◽  
Tae-Lin Ha ◽  
Sang-Im Park ◽  
...  

The cytotoxicity of magnetic nanoparticles-conjugated polymeric micelles encapsulated with an anticancer drug on cancer cells was enhanced by the synergistic effect of heat and the rapid release of the drug under an alternating magnetic field.


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