Continuously capturing circulating cancer cells

2019 ◽  
Vol 11 (489) ◽  
pp. eaax1730
Author(s):  
Rajan P. Kulkarni
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Circulating Cancer Cells

A wearable apheresis device allows for continuous and specific capture of circulating tumor cells.

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.

A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Automated Image Analysis ◽  
Rare Cancer ◽  
On Chip ◽  
Chip Analysis ◽  
Selection Of

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.

Circulating Tumor Cells: Diagnostic and Therapeutic Applications

2018 ◽  
Vol 20 (1) ◽  
pp. 329-352 ◽  
Author(s):  
Eric Lin ◽  
Thong Cao ◽  
Sunitha Nagrath ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Poor Prognosis ◽  
Experimental Therapeutics ◽  
Next Generation ◽  
Therapeutic Applications

Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.

Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model

Blood ◽  
2020 ◽  
Author(s):  
Manuel J Feinauer ◽  
Stefan W Schneider ◽  
Anna Sophie Berghoff ◽  
Jose Ramon Robador ◽  
Cedric Tehranian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Laser Scanning Microscopy ◽  
Clot Formation ◽  
Circulating Cancer Cells ◽  
Brain Microvessels ◽  
Plasmatic Coagulation ◽  
Cell Arrest ◽  
The Brain

Clinically relevant brain metastases (BM) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors are not well understood. Here, in vivo multiphoton laser-scanning microscopy (MPLSM) of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-time arrest. An extensive clot embedded approximately 20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, tissue factor-mediated thrombin generation by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low-molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and brain macrometastasis formation. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall BM formation. In conclusion, our data shows that plasmatic coagulation is activated early by intravascular tumor cells in the brain, with subsequent clot formation, discovering a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for BM prevention trials.

scholarly journals Mass Action Kinetic Model of Apoptosis by TRAIL-Functionalized Leukocytes

2018 ◽  
Author(s):  
Emily E. Lederman ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prolonged Exposure ◽  
Mass Action ◽  
New Approach ◽  
Membrane Bound ◽  
Soluble Trail ◽  
Kinetics Of ◽  
Coupled Reaction

1 AbstractBackgroundMetastasis through the bloodstream contributes to poor prognosis in many types of cancer. A unique approach to target and kill colon, prostate, and other epithelial-type cancer cells in the blood has been recently developed that causes circulating leukocytes to present the cancer-specific, liposome-bound Tumor Necrosis Factor (TNF)-related apoptosis inducing ligand (TRAIL) on their surface along with E – selectin adhesion receptors. This approach, demonstrated both in vitro with human blood and in mice, mimics the cytotoxic activity of natural killer cells. The resulting liposomal TRAIL-coated leukocytes hold promise as an effective means to neutralize circulating tumor cells that enter the bloodstream with the potential to form new metastases.ResultsThe computational biology study reported here examines the mechanism of this effective signal delivery, by considering the kinetics of the coupled reaction cascade, from TRAIL binding death receptor to eventual apoptosis. In this study, a collision of bound TRAIL with circulating tumor cells (CTCs) is considered and compared to a prolonged exposure of CTCs to soluble TRAIL. An existing computational model of soluble TRAIL treatment was modified to represent the kinetics from a diffusion-limited 3D reference frame into a 2D collision frame with advection and adhesion to mimic the E – selectin and membrane bound TRAIL treatment. Thus, the current model recreates the new approach of targeting cancer cells within the blood. The model was found to faithfully reproduce representative observations from experiments of liposomal TRAIL treatment under shear. The model predicts apoptosis of CTCs within 2 hr when treated with membrane bound TRAIL, while apoptosis in CTCs treated with soluble TRAIL proceeds much more slowly over the course of 10 hrs, consistent with previous experiments. Given the clearance rate of soluble TRAIL in vivo, this model predicts that the soluble TRAIL method would be rendered ineffective, as found in previous experiments.ConclusionThis study therefore indicates that the kinetics of the coupled reaction cascade of liposomal E – selectin and membrane bound TRAIL colliding with CTCs can explain why this new approach to target and kill cancer cells in blood is much more effective than its soluble counterpart.

scholarly journals Chemically modified plastic tube for high volume removal and collection of circulating tumor cells

2015 ◽  
Author(s):  
Angelo Gaitas ◽  
Gwangseong Kim
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
High Volume ◽  
Blood Stream ◽  
Plastic Tube ◽  
Chemically Modified ◽  
Stage Of Development ◽  
Flow Through

In this preliminary effort, we use a commercially available and chemically modified tube to selectively capture circulating tumor cells (CTCs) from the blood stream by immobilizing human anti-EpCAM antibodies on the tube's interior surface. We describe the steps required to modify a tube into a cancer cell capturing device. Using these simple modifications, at this proof-of-concept stage of development, we were able to capture about 85% of cancer cells from suspension and 44% of cancer cells from spiked whole blood, the capture percentage being dependent on the tube's length and the number of cancer cells present. Previous work by other researchers has focused on extracting small blood volumes and capturing CTCs with complicated micro-fluidic devices for diagnostic purposes. In addition, prior results of other researchers point to a possible reduction in metastasis achieved by removing CTCs from the bloodstream. We believe that with the utilization of appropriate tube lengths and procedures, we can ensure capture and removal of nearly the entire CTC population in whole blood. Following whole blood flow through the tube, the tube can be trypsinized to release the captured live CTCs for further analysis and testing.

Fabrication and Testing of a Magnetophoretic Bioseparation Chip for Isolation and Detection of Circulating Tumor Cells From Peripheral Blood

2019 ◽  
Author(s):  
Seth Jackson ◽  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Blood Sample ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Point Of Care ◽  
Magnetic Field Gradient ◽  
The Body ◽  
Target Cells ◽  
Economic Point

Abstract Significant research involving the isolation and detection of circulating tumor cells (CTCs) has become prevalent in the field of biomedicine. It plays a crucial role in the diagnosis and treatment of cancer and has made substantial strides in recent years. A major event in the timeline of cancer is metastasis, a set of occurrences where cells are shed from a cancerous site, then flow through the circulatory system and seed themselves throughout the body, forming secondary tumors. There are few observable symptoms in the early stages of metastasis and this fact severely limits clinical treatment. The fabrication and preliminary testing of a magnetophoretic bioseparation chip capable of isolating and detecting CTCs from peripheral blood, which can aid in early detection of metastases, is presented in this work. MCF7 breast cancer cells along with superparamagnetic microparticles, which are specifically coated with anti-EpCAM to bind to the cancer cells, are spiked into a blood sample. After the spiked blood sample is introduced into the biochip, a locally engineered magnetic field gradient captures the magnetically labeled cancer cells while the non-target cells are allowed to pass by. Once the target cells are isolated from the blood sample, flow cytometry is used to determine the recovery rate of the magnetophoretic device. The proposed device can operate at continuous flow rates magnitudes higher than other CTC isolation devices and is fabricated using much simpler methods which make it quite unique. These properties combined with greater than 80% recovery rates make the device quite favorable for economic point of care use in clinical applications.

scholarly journals Efficient Capture and Raman Analysis of Circulating Tumor Cells by Nano-Undulated AgNPs-rGO Composite SERS Substrates

Sensors ◽  
2020 ◽  
Vol 20 (18) ◽  
pp. 5089
Author(s):  
Jong-Eun Park ◽  
Nuri Oh ◽  
Hyeono Nam ◽  
Ji-Ho Park ◽  
Sanha Kim ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Electric Fields ◽  
Indium Tin Oxide ◽  
Hot Spot ◽  
Silver Nanowire ◽  
Sers Substrate

The analysis of circulating tumor cells (CTCs) in the peripheral blood of cancer patients is critical in clinical research for further investigation of tumor progression and metastasis. In this study, we present a novel surface-enhanced Raman scattering (SERS) substrate for the efficient capture and characterization of cancer cells using silver nanoparticles-reduced graphene oxide (AgNPs-rGO) composites. A pulsed laser reduction of silver nanowire-graphene oxide (AgNW-GO) mixture films induces hot-spot formations among AgNPs and artificial biointerfaces consisting of rGOs. We also use in situ electric field-assisted fabrication methods to enhance the roughness of the SERS substrate. The AgNW-GO mixture films, well suited for the proposed process due to its inherent electrophoretic motion, is adjusted between indium tin oxide (ITO) transparent electrodes and the nano-undulated surface is generated by applying direct-current (DC) electric fields during the laser process. As a result, MCF7 breast cancer cells are efficiently captured on the AgNPs-rGO substrates, about four times higher than the AgNWs-GO films, and the captured living cells are successfully analyzed by SERS spectroscopy. Our newly designed bifunctional substrate can be applied as an effective system for the capture and characterization of CTCs.

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