scholarly journals Inertial-Assisted Immunomagnetic Bioplatform towards Efficient Enrichment of Circulating Tumor Cells

Biosensors ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 183
Author(s):  
Yixing Gou ◽  
Jiawen Liu ◽  
Changku Sun ◽  
Peng Wang ◽  
Zheng You ◽  
...  
Keyword(s):  
Velocity Distribution ◽  
Numerical Simulations ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cross Section ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Cancer Biology ◽  
Inertial Effect ◽  
Immunomagnetic Beads

Serving as an effective biomarker in liquid biopsy, circulating tumor cells (CTCs) can provide an accessible source for cancer biology study. For the in-depth evaluation of CTCs in cancer analysis, their efficient enrichment is essential, owing to their low abundance in peripheral blood. In this paper, self-assembled immunomagnetic beads were developed to isolate CTCs from the ordered bundles of cells under the assistance of the spiral inertial effect. Parametric numerical simulations were performed to explore the velocity distribution in the cross section. Based on this chip, rare CTCs could be recovered under the throughput of 500 μL/min, making this device a valuable supplement in cancer analysis, diagnostics, and therapeutics.

scholarly journals Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients

Lab on a Chip ◽  
2019 ◽  
Vol 19 (11) ◽  
pp. 1899-1915 ◽  
Author(s):  
Masoud S. Loeian ◽  
Sadegh Mehdi Aghaei ◽  
Farzaneh Farhadi ◽  
Veeresh Rai ◽  
Hong Wei Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Purity ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Breast Cancer Patients ◽  
Multiple Phenotypes

We report the development of the nanotube-CTC-chip for isolation of circulating tumor cells of multiple phenotypes from peripheral blood.

Liquid biopsy: novel technologies and clinical applications

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Natalie Reimers ◽  
Klaus Pantel
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Clinical Applications ◽  
Novel Technologies ◽  
The Past

Abstract“Liquid biopsy” was introduced as a new diagnostic concept in 2010 for the analysis of circulating tumor cells (CTCs) and has been now extended to material (in particular DNA) released by tumor cells in the peripheral blood of cancer patients. Over the past decade, various methods have been developed to detect CTCs and ctDNA in the peripheral blood of cancer patients.

Quantification of activated and exhausted immune cell populations and simultaneous characterization of circulating tumor cells (CTCs) in peripheral blood of cancer patients receiving checkpoint inhibitor therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14033-e14033
Author(s):  
Gordon Vansant ◽  
Rachel Krupa ◽  
Robin Richardson ◽  
Priscilla Ontiveros ◽  
Jiyun Byun ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cell Populations ◽  
Ki 67 ◽  
Matched Samples

e14033 Background: Immune checkpoint inhibitors (ICIs) are becoming standard treatment options in many indications. However, a substantial portion of patients will not respond. Single biomarkers such as PD-L1 are insufficiently accurate to predict patient benefit. We sought to expand the Epic Sciences non-invasive liquid biopsy platform to identify predictive, peripheral blood biomarkers for ICIs using both molecular analyses of CTCs and immune cell changes. Methods: Blood samples from prostate, kidney, and bladder cancer patients treated with ICIs were collected at baseline and on-therapy and sent to Epic Sciences. Nucleated cells were plated on glass slides and stained with CTC (pan-CK, CD45, PD-L1 and DAPI) and immune panels for activation (CD4, CD8, Ki-67, and DAPI) and exhaustion (CD8, Ki-67, PD-1, Lag-3, Tim-3, and DAPI). Changes in populations of immune cells and circulating tumor cells were assessed using high throughput digital pathology. Results: CTCs were detected in 73% (24/33) patients, of which 12% (4/33) had PD-L1+ CTCs detected. No PD-L1+ CTCs were detected in the nine on-therapy samples tested. Of 14 patients with matched samples, 57% (8/14) patients had an increase in activated CD4+ leukocytes and 36% (5/14) patients had an increase in activated CD8+ leukocytes in on-therapy samples compared to baseline. The exhaustion assay was performed on a subset (6 of 14) of matched samples. In baseline and on-therapy samples, one patient had higher levels of exhausted CD8+ leukocytes compared to healthy donor controls, and two patients had lower levels versus controls. No change in exhausted CD8+ leukocytes was observed from baseline to on-therapy. Conclusions: We developed a liquid biopsy-based platform that can simultaneously measure biomarkers in CTCs and leukocytes from a single peripheral blood sample. Changes in activated and exhausted immune cell populations with ICI treatment were detected and PD-L1 expression on CTCs was evaluated. Efforts to further stratify immune and rare cell populations are ongoing.

scholarly journals Acoustic separation of circulating tumor cells

2015 ◽  
Vol 112 (16) ◽  
pp. 4970-4975 ◽  
Author(s):  
Peng Li ◽  
Zhangming Mao ◽  
Zhangli Peng ◽  
Lanlan Zhou ◽  
Yuchao Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Surface Acoustic Waves ◽  
Clinical Samples ◽  
Label Free ◽  
Blood Samples

Circulating tumor cells (CTCs) are important targets for cancer biology studies. To further elucidate the role of CTCs in cancer metastasis and prognosis, effective methods for isolating extremely rare tumor cells from peripheral blood must be developed. Acoustic-based methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contact-free sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients owing to technical constraints, insufficient throughput, and lack of long-term device stability. In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients. Our method uses tilted-angle standing surface acoustic waves. Parametric numerical simulations were performed to design optimum device geometry, tilt angle, and cell throughput that is more than 20 times higher than previously possible for such devices. We first validated the capability of this device by successfully separating low concentrations (∼100 cells/mL) of a variety of cancer cells from cell culture lines from WBCs with a recovery rate better than 83%. We then demonstrated the isolation of CTCs in blood samples obtained from patients with breast cancer. Our acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.

scholarly journals A Modified Method to Isolate Circulating Tumor Cells and Identify by a Panel of Gene Mutations in Lung Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199527
Author(s):  
Helin Wang ◽  
Jieqing Wu ◽  
Qi Zhang ◽  
Jianqing Hao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Detection Rate ◽  
Target Genes ◽  
White Blood Cells ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Immunomagnetic Beads ◽  
Membrane Rupture

The CellSearch system is the only FDA approved and successful used detection technology for circulating tumor cells(CTCs). However, the process for identification of CTCs by CellSearch appear to damage the cells, which may adversely affects subsequent molecular biology assays. We aimed to explore and establish a membrane-preserving method for immunofluorescence identification of CTCs that keeping the isolated cells intact. 98 patients with lung cancer were enrolled, and the efficacy of clinical detection of CTCs was examined. Based on the CellSearch principle, we optimized an anti-EpCAM antibody and improved cell membrane rupture. A 5 ml peripheral blood sample was used to enrich CTCs with EpCAM immunomagnetic beads. Fluorescence signals were amplified with secondary antibodies against anti-EpCAM antibody attached on immunomagnetic beads. After identifying CTCs, single CTCs were isolated by micromanipulation. To confirm CTCs, genomic DNA was extracted and amplified at the single cell level to sequence 72 target genes of lung cancer and analyze the mutation copy number variations (CNVs) and gene mutations. A goat anti-mouse polyclonal antibody conjugated with Dylight 488 was selected to stain tumor cells. We identified CTCs based on EpCAM+ and CD45+ cells to exclude white blood cells. In the 98 lung cancer patients, the detection rate of CTCs (≥1 CTC) per 5 ml blood was 87.76%, the number of detections was 1–36, and the median was 2. By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.

scholarly journals High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1656 ◽  
Author(s):  
Etienne Buscail ◽  
Catherine Alix-Panabières ◽  
Pascaline Quincy ◽  
Thomas Cauvin ◽  
Alexandre Chauvet ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Neoadjuvant Treatment ◽  
Digital Pcr ◽  
Portal Blood ◽  
Ductal Adenocarcinoma ◽  
Clinical Value ◽  
Liquid Biopsies

Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.

scholarly journals Molecular Detection of Peripheral Blood Breast Cancer mRNA Transcripts as a Surrogate Biomarker for Circulating Tumor Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74079 ◽  
Author(s):  
Adriana Lasa ◽  
Arnal Garcia ◽  
Carmen Alonso ◽  
Pilar Millet ◽  
Mónica Cornet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Molecular Detection ◽  
Mrna Transcripts
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