scholarly journals A microfluidic device for label-free isolation of tumor cell clusters from unprocessed blood samples

2019 ◽  
Vol 13 (4) ◽  
pp. 044111 ◽  
Author(s):  
Nabiollah Kamyabi ◽  
Jonathan Huang ◽  
Jaewon J. Lee ◽  
Vincent Bernard ◽  
Alexander Semaan ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Microfluidic Device ◽  
Label Free ◽  
Blood Samples ◽  
Cell Clusters

scholarly journals A microfluidic device for label-free, physical capture of circulating tumor cell clusters

2015 ◽  
Vol 12 (7) ◽  
pp. 685-691 ◽  
Author(s):  
A Fatih Sarioglu ◽  
Nicola Aceto ◽  
Nikola Kojic ◽  
Maria C Donaldson ◽  
Mahnaz Zeinali ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Microfluidic Device ◽  
Circulating Tumor Cell ◽  
Label Free ◽  
Cell Clusters

scholarly journals Design and production of a novel microfluidic device for the capture and isolation of circulating tumor cell clusters

AIP Advances ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 065313
Author(s):  
Sebastian W. Shaner ◽  
Jeffrey K. Allen ◽  
Martina Felderman ◽  
Evan T. Pasko ◽  
Carina D. Wimer ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Microfluidic Device ◽  
Circulating Tumor Cell ◽  
Cell Clusters ◽  
Design And Production

High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics

Lab on a Chip ◽  
2014 ◽  
Vol 14 (14) ◽  
pp. 2525-2538 ◽  
Author(s):  
Shaofei Shen ◽  
Chao Ma ◽  
Lei Zhao ◽  
Yaolei Wang ◽  
Jian-Chun Wang ◽  
...  
Keyword(s):  
Microfluidic Device ◽  
High Throughput ◽  
Steric Hindrance ◽  
Cell Separation ◽  
Label Free ◽  
Inertial Microfluidics ◽  
Blood Samples ◽  
Rare Cells

We present a multistage microfluidic device for continuous label-free separation of rare cells using a combination of inertial microfluidics and steric hindrance.

scholarly journals Dissemination of Circulating Tumor Cell Clusters Occurs Early in Non‑metastatic Breast Cancer Patients

2021 ◽  
Author(s):  
Carolina Reduzzi ◽  
Serena Di Cosimo ◽  
Lorenzo Gerratana ◽  
Rosita Motta ◽  
Antonia Martinetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cell ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Circulating Tumor Cell ◽  
Cluster Detection ◽  
Her2 Positive ◽  
Blood Samples ◽  
Cell Clusters

Abstract Background: Metastatic spreading is promoted by cancer cell seeding from the primary tumor into the bloodstream. In patients with metastatic breast cancer (MBC), the clinical relevance of circulating tumor cell clusters (CTC-clusters) has been extensively reported, while their study in earlier stages is limited. Several methods, besides the FDA-cleared CellSearch®, limited to the detection of epithelial-enriched clusters, can be used for the detection of CTC-clusters. We hypothesize that resorting to marker-independent approaches can improve CTC-cluster detection. Methods: Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, ScreenCell® filters. The number of CTC-clusters was compared among the technologies and analyzed in relation to patient characteristics and outcome. Results: In spiked-in samples, the 3 technologies showed similar capability of recover epithelial mammospheres, whereas, in a series of 19 clinical samples processed in parallel with the CellSearch® and CellSieve™ filters (that allow the detection of both epithelial and non-epithelial clusters), CTC-clusters were detected in 53% of samples with the CellSearch®, versus 79% and 84% with the CellSieve™, when considering only epithelial or both epithelial and non-epithelial clusters, respectively. Next, blood samples from 37 non-metastatic breast cancer (NMBC) and 23 MBC patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification of clusters based on cytomorphological criteria. At baseline, CTC-clusters were detected in 70% of NMBC cases and in 20% of MBC patients (median number= 2, range 0–20, versus 0, range 0‑15, P =0.0015). Among NMBC patients, clusters were slightly higher in women with node-positive than node‑negative status (0 versus 3, P =0.1110 ) and were more frequently observed in women with luminal‑like and triple-negative tumors than in patients with HER2-positive disease (median CTC-cluster number =4, 5, and 0 for luminal‑like, triple-negative, and HER2-positive BC, respectively, P =0.0467). Conclusions: We demonstrated that CTC-cluster detection can be improved by a marker-independent enrichment and identification, and we reported that CTC-clusters are more frequently detected in NMBC than in MBC patients, suggesting that dissemination of CTC-clusters is an early event in BC natural history.

A microfluidic device with integrated impedance detection for λ-DNA

2003 ◽  
Vol 773 ◽  
Author(s):  
Myung-Il Park ◽  
Jonging Hong ◽  
Dae Sung Yoon ◽  
Chong-Ook Park ◽  
Geunbae Im
Keyword(s):  
Microfluidic Device ◽  
Electrochemical Impedance ◽  
Direct Detection ◽  
Full Potential ◽  
Label Free ◽  
Buffer Solution ◽  
Detection Systems ◽  
Significant Difference ◽  
Detection Of Biomolecules ◽  
Impedance Magnitude

AbstractThe large optical detection systems that are typically utilized at present may not be able to reach their full potential as portable analysis tools. Accurate, early, and fast diagnosis for many diseases requires the direct detection of biomolecules such as DNA, proteins, and cells. In this research, a glass microchip with integrated microelectrodes has been fabricated, and the performance of electrochemical impedance detection was investigated for the biomolecules. We have used label-free λ-DNA as a sample biomolecule. By changing the distance between microelectrodes, the significant difference between DW and the TE buffer solution is obtained from the impedance-frequency measurements. In addition, the comparison for the impedance magnitude of DW, the TE buffer, and λ-DNA at the same distance was analyzed.

102 Cord-blood derived NK cells, and CAR-T cells, an attractive improved immunotherapy treatment to be considered for hematological malignancies

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A113-A113
Author(s):  
Mireia Bachiller García ◽  
Lorena Pérez-Amill ◽  
Anthony Battram ◽  
Alvaro Urbano-Ispizua ◽  
Beatriz Martín-Antonio
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Cord Blood ◽  
Immune Cells ◽  
In Vivo Models ◽  
Cell Clusters ◽  
Cytotoxicity Assays ◽  
Anti Tumor Activity

BackgroundMultiple myeloma (MM) remains an incurable hematological malignancy where a proportion of patients relapse or become refractory to current treatments. Administration of autologous T cells modified with a chimeric antigen receptor (CAR) against B cell maturation antigen (BCMA) has achieved high percentages of complete responses. Unfortunately, the lack of persistence of CART-BCMA cells in the patient leads to relapses. On the other side, cord-blood derived natural killer cells (CB-NK) is an off-the-shelf cellular immunotherapy option to treat cancer patients with high potential due to their anti-tumor activity. However, clinical results in patients up to date have been sub-optimal. Whereas CB-NK are innate immune cells and their anti-tumor activity is developed in a few hours, CART cells are adaptive immune cells and their activity develops at later time points. Moreover, we previously described that CB-NK secrete inflammatory proteins that promote the early formation of tumor-immune cell clusters bringing cells into close contact and thus, facilitating the anti-tumor activity of T cells. Therefore, we hypothesized that the addition of a small number of CB-NK to CART cells would improve the anti-tumor activity and increase the persistence of CART cells.MethodsT cells transduced with a humanized CAR against BCMA and CB-NK were employed at 1:0.5 (CART:CB-NK) ratio. Cytotoxicity assays, activation markers and immune-tumor cell cluster formation were evaluated by flow cytometry and fluorescence microscopy. In vivo models were performed in NSG mice.ResultsThe addition of CB-NK to CART cells demonstrated higher anti-MM efficacy at low E:T ratios during the first 24h and in long-term cytotoxicity assays, where the addition of CB-NK to CART cells achieved complete removal of tumor cells. Analysis of activation marker CD69 and CD107a degranulation from 4h to 24h of co-culturing proved differences only at 4h, where CD69 and CD107a in CART cells were increased when CB-NK were present. Moreover, CB-NK accelerated an increased formation of CART-tumor cell clusters facilitating the removal of MM cells. Of note, CB-NK addition did not increase total TNFα and IFNγ production. Finally, an in vivo model of advanced MM with consecutive challenge to MM cells evidenced that the addition of CB-NK achieved the highest efficacy of the treatment.ConclusionsOur results suggest that the addition of ‘off-the-shelf’ CB-NK to CART cells leads to a faster and earlier immune response of CART cells with higher long-term maintenance of the anti-tumor response, suggesting this combinatorial therapy as an attractive immunotherapy option for MM patients.

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