Dataset Information

Cancer cell enrichment on a centrifugal microfluidic platform using hydrodynamic and magnetophoretic techniques.

ABSTRACT: Isolation of rare cancer cells is one of the important and valuable stages of cancer research. Regarding the rarity of cancer cells in blood samples, it is important to invent an efficient separation device for cell enrichment. In this study, two centrifugal microfluidic devices were designed and fabricated for the isolation of rare cancer cells. The first design (passive plan) employs a contraction-expansion array (CEA) microchannel which is connected to a bifurcation region. This device is able to isolate the target cells through inertial effects and bifurcation law. The second design (hybrid plan) also utilizes a CEA microchannel, but instead of using the bifurcation region, it is reinforced by a stack of two permanent magnets to capture the magnetically labeled target cells at the end of the microchannel. These designs were optimized by numerical simulations and tested experimentally for isolation of MCF-7 human breast cancer cells from the population of mouse fibroblast L929 cells. In order to use the hybrid design, magnetite nanoparticles were attached to the MCF-7 cells through specific Ep-CAM antibodies, and two permanent magnets of 0.34 T were utilized at the downstream of the CEA microchannel. These devices were tested at different disk rotational speeds and it was found that the passive design can isolate MCF-7 cells with a recovery rate of 76% for the rotational speed of 2100 rpm while its hybrid counterpart is able to separate the target cells with a recovery rate of 85% for the rotational speed of 1200 rpm. Although the hybrid design of separator has a better separation efficiency and higher purity, the passive one has no need for a time-consuming process of cell labeling, occupies less space on the disk, and does not impose additional costs and complexity.

SUBMITTER: Shamloo A

PROVIDER: S-EPMC7820336 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cancer cell enrichment on a centrifugal microfluidic platform using hydrodynamic and magnetophoretic techniques.

Shamloo Amir A Naghdloo Amin A Besanjideh Mohsen M

Scientific reports 20210121 1

Isolation of rare cancer cells is one of the important and valuable stages of cancer research. Regarding the rarity of cancer cells in blood samples, it is important to invent an efficient separation device for cell enrichment. In this study, two centrifugal microfluidic devices were designed and fabricated for the isolation of rare cancer cells. The first design (passive plan) employs a contraction-expansion array (CEA) microchannel which is connected to a bifurcation region. This device is abl ...[more]

PMID: 33479404

Similar Datasets

Project description:BackgroundBiomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness.Methodology/principal findingsBy creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies.Conclusions/significanceThe microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy.

Project description:Invasion of the extracellular matrix is a critical step in the colonization of metastatic tumors. The invasion process is thought to be driven by both chemokine signaling and interactions between invading cancer cells and physical components of the metastatic niche, including endothelial cells that line capillary walls and serve as a barrier to both diffusion and invasion of the underlying tissue. Transwell chambers, a tool for generating artificial chemokine gradients to induce cell migration, have facilitated recent work to investigate the chemokine contributions to matrix invasion. These chambers, however, are poorly designed for imaging, which limits their use in investigating the physical cell-cell and cell-matrix interactions driving matrix invasion. Microfluidic devices offer a promising model in which the invasion process can be imaged. Many current designs, however, have limited surface areas and possess intricate geometries that preclude the use of standard staining protocols to visualize cells and matrix proteins. In this work, we present a novel microfluidic platform for imaging cell-cell and cell-matrix interactions driving metastatic cancer cell matrix invasion. Our model is applied to investigate how endothelial cell-secreted matrix proteins and the physical endothelial monolayer itself interact with invading metastatic breast cancer cells to facilitate invasion of an underlying type I collagen gel. The results show that matrix invasion of metastatic breast cancer cells is significantly enhanced in the presence of live endothelial cells. Probing this interaction further, our platform revealed that, while the fibronectin-rich matrix deposited by endothelial cells was not sufficient to drive invasion alone, metastatic breast cancer cells were able to exploit components of energetically inactivated endothelial cells to gain entry into the underlying matrix. These findings reveal novel cell-cell interactions driving a key step in the colonization of metastatic tumors and have important implications for designing drugs targeted at preventing cancer metastasis.

Project description:Increasing antibiotic resistance in pathogenic microorganisms has led to renewed interest in bacteriophage therapy in both humans and animals. A "Trojan Horse" approach utilizing liposome encapsulated phages may facilitate access to phagocytic cells infected with intracellular pathogens residing therein, e.g., to treat infections caused by Mycobacterium tuberculosis, Listeria, Salmonella, and Staphylococcus sp. Additionally, liposome encapsulated phages may adhere to and diffuse within mucosa harboring resistant bacteria which are challenges in treating respiratory and gastrointestinal infections. Orally delivered phages tend to have short residence times in the gastrointestinal tract due to clinical symptoms such as diarrhea; this may be addressed through mucoadhesion of liposomes. In the present study we have evaluated the use of a microfluidic based technique for the encapsulation of bacteriophages in liposomes having mean sizes between 100 and 300 nm. Encapsulation of two model phages was undertaken, an Escherichia coli T3 podovirus (size ~65 nm) and a myovirus Staphylococcus aureus phage K (capsid head ~80 nm and phage tail length ~200 nm). The yield of encapsulated T3 phages was 109 PFU/ml and for phage K was much lower at 105 PFU/ml. The encapsulation yield for E. coli T3 phages was affected by aggregation of T3 phages. S. aureus phage K was found to interact with the liposome lipid bilayer resulting in large numbers of phages bound to the outside of the formed liposomes instead of being trapped inside them. We were able to inactivate the liposome bound S. aureus K phages whilst retaining the activity of the encapsulated phages in order to estimate the yield of microfluidic encapsulation of large tailed phages. Previous published studies on phage encapsulation in liposomes may have overestimated the yield of encapsulated tailed phages. This overestimation may affect the efficacy of phage dose delivered at the site of infection. Externally bound phages would be inactivated in the stomach acid resulting in low doses of phages delivered at the site of infection further downstream in the gastrointestinal tract.

Dataset Information

Cancer cell enrichment on a centrifugal microfluidic platform using hydrodynamic and magnetophoretic techniques.

Publications

Cancer cell enrichment on a centrifugal microfluidic platform using hydrodynamic and magnetophoretic techniques.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets