Homogeneous Visual and Fluorescence Detection of Circulating Tumor Cells in Clinical Samples via Selective Recognition Reaction and Enzyme-Free Amplification

ACS Nano ◽  
2021 ◽  
Author(s):  
Piaopiao Chen ◽  
Yue Wang ◽  
Yaqin He ◽  
Ke Huang ◽  
Xiu Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Fluorescence Detection ◽  
Selective Recognition ◽  
Clinical Samples

scholarly journals The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1119
Author(s):  
Ivonne Nel ◽  
Erik W. Morawetz ◽  
Dimitrij Tschodu ◽  
Josef A. Käs ◽  
Bahriye Aktas
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Hematopoietic Cells ◽  
Surrogate Marker ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Shape Restoration

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.

Magnetic “Squashing” of Circulating Tumor Cells on Plasmonic Substrates for Ultrasensitive NIR Fluorescence Detection

Small Methods ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. 1800474 ◽  
Author(s):  
Ru Zhang ◽  
Biao Le ◽  
Wei Xu ◽  
Kai Guo ◽  
Xuming Sun ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Fluorescence Detection ◽  
Nir Fluorescence

Abstract 6442: Investigation of custom biomarkers on circulating tumor cells from clinical samples using RarePlex®Developer Kits

2020 ◽  
Author(s):  
Edward Lo ◽  
Daniel Campton ◽  
Arturo Ramirez ◽  
Lillian Costandy ◽  
Brady Gardner ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Samples

scholarly journals Pre-Analytical and Analytical Variables of Label-Independent Enrichment and Automated Detection of Circulating Tumor Cells in Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 442 ◽  
Author(s):  
Claudia Koch ◽  
Simon A. Joosse ◽  
Svenja Schneegans ◽  
Okka J. W. Wilken ◽  
Melanie Janning ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Cell Line ◽  
Response To Therapy ◽  
Clinical Samples ◽  
Blood Collection ◽  
Multiple Parameters ◽  
Healthy Donors

Circulating tumor cells (CTCs) are promising tools for risk prediction and the monitoring of response to therapy in cancer patients. Within the EU/IMI CANCER-ID consortium, we validated CTC enrichment systems for future inclusion into clinical trials. Due to the known heterogeneity of markers expressed on CTCs, we tested the Parsortix® system (ANGLE plc) which enables label-independent CTC enrichment from whole blood based on increased size and deformability of these tumor cells compared to leukocytes. We performed extensive comparisons both with spiked-in blood models (i.e., MDA-MB-468 tumor cell line cells spiked at very low concentration into blood from healthy donors) and validated the protocol on actual clinical samples from breast, lung, and gastrointestinal cancer patients to define optimal conditions for CTC enrichment. Multiple parameters including cassette gap, separation pressure, and cell fixatives were compared in parallel. Also, the compatibility of blood collection tubes with whole genome amplification of isolated tumor cells was demonstrated and we furthermore established a workflow for semi-automated CTC detection using a quantitative cell imager. The established workflow will contribute to supporting the use of size-based CTC enrichment platforms in clinical trials testing the clinical validity and utility of CTCs for personalized medicine.

scholarly journals Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells

2014 ◽  
Vol 60 (2) ◽  
pp. 323-333 ◽  
Author(s):  
Ramdane A Harouaka ◽  
Ming-Da Zhou ◽  
Yin-Ting Yeh ◽  
Waleed J Khan ◽  
Avisnata Das ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Ex Vivo ◽  
Cell Damage ◽  
Flexible Structures ◽  
Capture Efficiency ◽  
Clinical Samples ◽  
Blood Samples ◽  
Whole Blood Samples

Abstract BACKGROUND The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. METHODS Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. RESULTS The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples. CONCLUSIONS The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.

scholarly journals EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis

2021 ◽  
Author(s):  
Jenna Kitz ◽  
David Goodale ◽  
Carl Postenka ◽  
Lori E. Lowes ◽  
Alison L. Allan
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Technical Note ◽  
Clinical Samples ◽  
Blood Samples ◽  
Mesenchymal Transition ◽  
Clinical Models ◽  
Human Blood Samples

AbstractCirculating tumor cells (CTCs) present an opportunity to detect/monitor metastasis throughout disease progression. The CellSearch® is currently the only FDA-approved technology for CTC detection in patients. The main limitation of this system is its reliance on epithelial markers for CTC isolation/enumeration, which reduces its ability to detect more aggressive mesenchymal CTCs that are generated during metastasis via epithelial-to-mesenchymal transition (EMT). This Technical Note describes and validates two EMT-independent CTC analysis protocols; one for human samples using Parsortix® and one for mouse samples using VyCap. Parsortix® identifies significantly more mesenchymal human CTCs compared to the clinical CellSearch® test, and VyCap identifies significantly more CTCs compared to our mouse CellSearch® protocol regardless of EMT status. Recovery and downstream molecular characterization of CTCs is highly feasible using both Parsortix® and VyCap. The described CTC protocols can be used by investigators to study CTC generation, EMT and metastasis in both pre-clinical models and clinical samples.

Janus micromotors for motion-capture-ratiometric fluorescence detection of circulating tumor cells

2020 ◽  
Vol 382 ◽  
pp. 123041 ◽  
Author(s):  
Long Zhao ◽  
Yuan Liu ◽  
Songzhi Xie ◽  
Pan Ran ◽  
Jiaojun Wei ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Motion Capture ◽  
Fluorescence Detection ◽  
Ratiometric Fluorescence
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