scholarly journals Integrated Microfluidic Device for Enrichment and Identification of Circulating Tumor Cells from the Blood of Patients with Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Wentao Su ◽  
Hao Yu ◽  
Lei Jiang ◽  
Wenwen Chen ◽  
Hongjing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Circulating Tumor Cell ◽  
Clinical Samples ◽  
Leukocyte Depletion ◽  
Healthy Donors ◽  
Integrated Device ◽  
Optimized Conditions

Integrated device with high purity for circulating tumor cell (CTC) identification has been regarded as a key goal to make CTC analysis a “bench-to-bedside” technology. Here, we have developed a novel integrated microfluidic device that can enrich and identify the CTCs from the blood of patients with colorectal cancer. To enrich CTCs from whole blood, microfabricated trapping chambers were included in the miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and normal blood cells. Microvalves were also introduced sequentially in the device, enabling automatic CTC enrichment as well as immunostaining reagent delivery. Under optimized conditions, the whole blood spiked with caco-2 cells passing through the microfluidic device after leukocyte depletion and approximately 73% of caco-2 cells were identified by epithelial cell adhesion molecule (EpCAM) staining. In clinical samples, CTCs were detectable from all patients with advanced colorectal cancer within 3 h. In contrast, the number of CTCs captured on the device from the blood of healthy donors was significantly lower than that from the patients, suggesting the utilization of the integrated device for further molecular analyses of CTCs.

scholarly journals Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

Lab on a Chip ◽  
2019 ◽  
Vol 19 (20) ◽  
pp. 3427-3437 ◽  
Author(s):  
Chia-Heng Chu ◽  
Ruxiu Liu ◽  
Tevhide Ozkaya-Ahmadov ◽  
Mert Boya ◽  
Brandi E. Swain ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
3D Printed

A monolithic 3D-printed microfluidic device integrated with stacked layers of functionalized leukodepletion channels and microfiltration for the negative enrichment of circulating tumor cells directly from clinically relevant volumes of whole blood.

scholarly journals Multi-layer assembly of cellulose nanofibrils in a microfluidic device for the selective capture and release of viable tumor cells from whole blood

Nanoscale ◽  
2020 ◽  
Vol 12 (42) ◽  
pp. 21788-21797
Author(s):  
Tharagan Kumar ◽  
Ruben R. G. Soares ◽  
Leyla Ali Dholey ◽  
Harisha Ramachandraiah ◽  
Negar Abbasi Aval ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Cellulose Nanofibrils ◽  
Layer By Layer ◽  
Layer By Layer Assembly ◽  
Viable Tumor ◽  
Capture And Release ◽  
Layer Assembly

A microfluidic device modified with a layer-by-layer assembly of cellulose nanofibrils allows efficient capture and enzymatic release of tumor cells.

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 Continuous Separation of Circulating Tumor Cells from Whole Blood Using a Slanted Weir Microfluidic Device

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 200 ◽  
Author(s):  
Yousang Yoon ◽  
Jusin Lee ◽  
Moonsoo Ra ◽  
Hyeokshin Gwon ◽  
Seungwon Lee ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Tumor Heterogeneity ◽  
Separation Efficiency ◽  
Cancer Cell Line ◽  
Analysis Tool ◽  
Surface Molecules ◽  
Clinical Potential

The separation of circulating tumor cells (CTCs) from the peripheral blood is an important issue that has been highlighted because of their high clinical potential. However, techniques that depend solely on tumor-specific surface molecules or just the larger size of CTCs are limited by tumor heterogeneity. Here, we present a slanted weir microfluidic device that utilizes the size and deformability of CTCs to separate them from the unprocessed whole blood. By testing its ability using a highly invasive breast cancer cell line, our device achieved a 97% separation efficiency, while showing an 8-log depletion of erythrocytes and 5.6-log depletion of leukocytes. We also developed an image analysis tool that was able to characterize the various morphologies and differing deformability of the separating cells. From the results, we believe our system possesses a high potential for liquid biopsy, aiding future cancer research.

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 Bicentric evaluation of stabilizing sampling tubes for assessment of monocyte HLA-DR expression in clinical samples

2021 ◽  
Author(s):  
guillaume monneret
Keyword(s):  
Flow Cytometry ◽  
Whole Blood ◽  
Human Leukocyte ◽  
Clinical Samples ◽  
University Hospitals ◽  
Short Delay ◽  
Leukocyte Antigen ◽  
Hla Dr ◽  
Healthy Donors ◽  
Flow Cytometry Staining

Background. Diminished expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR), measured by standardized flow cytometry procedure, is a reliable indicator of immunosuppression in severely injured intensive care unit patients. As such, it is used as stratification criteria in clinical trials evaluating novel immunostimulating therapies. Pre-analytical constraints relative to the short delay between blood sampling and flow cytometry staining have nevertheless limited its use in multicentric studies. The objective of the present work was to compare mHLA-DR expression between whole blood samples simultaneously drawn in EDTA or Cyto-Chex BCT tubes. Methods. In 2 university hospitals, mHLA-DR was assessed in fresh whole blood from septic patients (n = 12) and healthy donors (n = 6) simultaneously sampled on EDTA and Cyto-Chex BCT tubes. Staining was performed immediately after sampling and after blood storage at room temperature. Results. We observed the remarkable stability of mHLA-DR results when blood was collected in Cyto-Chex BCT tubes (until 48-72 h). On baseline values, despite good correlation between tubes (r = 0.98, p< 0.001), mHLA-DR expression was systematically lower with Cyto-Chex BCT. Conclusion. The present reports confirms the great potential of Cyto-Chex BCT tubes to delay mHLA-DR staining in centers without rapid access to flow cytometry facilities. However, a 30 % gap exists between results obtained with EDTA and Cyto-Chex BCT tubes. As current thresholds for clinical decisions were obtained with EDTA samples, further studies are needed to confirm clinical thresholds with Cyto-Chex BCT tubes.

scholarly journals Enrichment of Circulating Tumor Cells from Whole Blood Using a Microfluidic Device for Sequential Physical and Magnetophoretic Separations

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 481 ◽  
Author(s):  
Jusin Lee ◽  
Onejae Sul ◽  
Seung-Beck Lee
Keyword(s):  
Specific Surface ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Blood Cells ◽  
Magnetic Beads ◽  
Separation Efficiency ◽  
White Blood Cells

Based on their high clinical potential, the isolation and enrichment of rare circulating tumor cells (CTCs) from peripheral blood cells has been widely investigated. There have been technical challenges with CTC separation methods using solely cancer-specific surface molecules or just using physical properties of CTCs, as they may suffer from heterogeneity or lack of specificity from overlapping physical characteristics with leukocytes. Here, we integrated an immunomagnetic-based negative enrichment method that utilizes magnetic beads attached to leukocyte-specific surface antigens, with a physical separation method that utilizes the distinct size and deformability of CTCs. By manipulating the pressure distribution throughout the device and balancing the drag and magnetic forces acting on the magnetically labeled white blood cells (WBCs), the sequential physical and magnetophoretic separations were optimized to isolate intact cancer cells, regardless of heterogeneity from whole blood. Using a breast cancer cell line in whole blood, we achieved 100% separation efficiency for cancer cells and an average of 97.2% for WBCs, which resulted in a 93.3% average separation purity. The experimental results demonstrated that our microfluidic device can be a promising candidate for liquid biopsy and can be a vital tool for aiding future cancer research.

scholarly journals Fast and efficient microfluidic cell filter for isolation of circulating tumor cells from unprocessed whole blood of colorectal cancer patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Silvina Ribeiro-Samy ◽  
Marta I. Oliveira ◽  
Thais Pereira-Veiga ◽  
Laura Muinelo-Romay ◽  
Sandra Carvalho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Colorectal Cancer Patients

scholarly journals Proteomic indicators of oxidation and hydration state in colorectal cancer

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2238 ◽  
Author(s):  
Jeffrey M. Dick
Keyword(s):  
Colorectal Cancer ◽  
Essential Feature ◽  
Microbial Community Composition ◽  
Compositional Analysis ◽  
Clinical Samples ◽  
Systematic Change ◽  
Bacterial Genomes ◽  
Healthy Donors ◽  
Relative Potential ◽  
Related Proteins

New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer. Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue (${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$) is computed by writing the overall formation reactions of proteins from basis species. Using results reported in proteomic studies of clinical samples, many datasets exhibit higher meanZCor ${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$ of proteins in carcinoma or adenoma compared to normal tissue. In contrast, average protein compositions in bacterial genomes often have lowerZCfor bacteria enriched in fecal samples from cancer patients compared to healthy donors. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2that reflect the compositional differences. The compositional analysis suggests that a systematic change in chemical composition is an essential feature of cancer proteomes, and the thermodynamic descriptions show that the observed proteomic transformations in host tissue could be promoted by relatively high microenvironmental oxidation and hydration states.

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