Author: Nika Nikbakht
Publisher:
ISBN: 9781321854633
Category :
Languages : en
Pages : 67
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Book Description
Circulating tumor cells (CTCs) are cells that shed into the vasculature from a primary tumor and circulate in the bloodstream. CTCs can be used to elucidate the molecular characterization of the tumor cells and to gauge the efficiency of therapeutic treatment in metastatic carcinoma patients. They can also be used to determine the primary site of the tumor in areas where the tumor is undetectable with traditional oncological imaging. The detection of CTCs has a substantial value for prognostic and therapeutic implications, but they are not easily detected because of their low cell count. Because microfluidic devices are useful for cell detection and diagnosis, can be easily obtained, and are less invasive than tissue biopsies, we have developed a microfluidic platform to capture CTCs using multiple capture targets to achieve a higher cell capture. We can selectively isolate the cancer cells using specific antibodies to the antigen capture target on the surface of malignant cells. The capture efficiency was evaluated by the flow rate, cell count, and antibody immobilization. Cancer cell lines that were known to have high expression for targeted ligands, specifically HER2, EGFR, EpCAM, and MUC-1, were tested with antibodies specific to these ligands. We obtained capture efficiency with these different capture targets on a single channel. This allowed us to develop a device with four parallel capture channels to run in series with the anticipation of achieving higher cell capture.
Author: Shrutilaya Karunanidhi
Publisher:
ISBN: 9781303229893
Category :
Languages : en
Pages : 68
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Book Description
Cells that break off from the primary tumor, known as circulating tumor cells are often the cause of metastasis in cancer patients. Their isolation and characterization is pivotal for various reasons such as molecular characterization of the tumor cells, treatment monitoring, and also to determine the primary site of the tumor in cases where the tumor itself is undetectable, however, this task remains a major challenge as these cells are extremely rare in the blood vessels. Numerous research groups have presented microfluidic approaches that are capable of isolation and capture of rare cells. Recently, inertial microfluidics is one such approach that has gained much attention for this application. In these systems, various hydrodynamic forces generated in the microchannels are used for size-based focusing of particles into distinct streams. Based on this concept, we developed fourteen different microfluidic devices using poly(dimethylsiloxane) (PDMS) polymer. Each device had a typical set of nine parameters like channel width, location of branches, position of first branch and number of loops. The devices were tested with a binary mixture of polystyrene beads as the sample solution at various flow rates and concentration ratios. Several hypotheses were tested and inferences were drawn to determine the most efficient design in terms of the capture efficiency and isolation efficiency of the device. The final device design achieved an isolation and capture efficiency of>90%, thereby, making it a better alternate for cancer screening.
Author: Julien Autebert
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Sweta Gupta
Publisher:
ISBN: 9781124880983
Category :
Languages : en
Pages : 48
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Book Description
Viable tumor cells that are disseminated in the blood stream, also known as circulating tumor cells (CTCs), are often the cause of metastasis in cancer patients. Although these cells are rare in blood, they can be isolated and used to study various aspects of the tumor such as molecular characterization of the tumor cells, effectiveness of treatment therapies in metastatic carcinoma patients, and also to determine the primary site of the tumor in cases where the tumor itself is undetectable. Previous researches have demonstrated microfluidic platforms capable of selectively capturing rare cells from raw liquid samples, using adhesion-mediated binding of the target cells with complementary ligand proteins that are immobilized on arrays of micropillars. In these systems, the circular or square shaped micropillars which provide increased surface area for cell-protein interactions, were fabricated on a silicon chip by an expensive and skillfully demanding technique called deep reactive ion etching (DRIE) [1,2]. Based on the concept of protein-coated micropillars, we used soft lithographic techniques to develop microfluidic devices using poly(dimethylsiloxane) (PDMS) polymer. PDMS molds consisting of thirty five different device designs with varied micropillar features like shape, size, spacing, and array arrangement were fabricated. The devices were tested with five different cancer cell lines, at different flow rates and cell concentrations, and a comparative study was performed to determine the most efficient design in terms of cell capture efficiency. Some designs achieved mean capture yields of>45%, thereby making this low-cost, quick and easy technique an attractive cancer screening tool.
Author: Hashem Mohammad Abul
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages :
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Book Description
Circulating Tumor Cells (CTCs) are potential indicators of cancer. Detection of CTCs is important for diagnosing cancer at an early stage and predicting the effectiveness of cancer treatment. Recent progress in the development of microfluidic chips has inaugurated a new possibility for designing diagnostic devices for early cancer detection. Among various devices, deformation-based CTC microchips have shown a strong promise for CTC detection due to its simplicity and low cost. This type of devices involves a process where CTCs are trapped while allowing more deformable blood cells to squeeze through the filtration geometry at the specified operating pressure. Fundamental understanding of CTC passing event through a micro-filtering channel seems to be a promising direction in studying these microdevicessince it helps optimize the microfilter design for achieving high isolation purity and capture efficiency. Along with the experimental studies, numerical simulation emerges as a powerful tool to predict the behavior of a cell inside a microfilter, and may deliver important insights to optimize the processes by saving time and cost. First, the CTC squeezing process through a microfluidic filtering channel is studied by modeling the CTC as a simple liquid droplet. Cell modeling employed both Newtonian and non-Newtonian approaches to simplify the model and investigating different biophysical properties. Detailed microscopic multiphase flow characteristics regarding the filtering process are discussed including the pressure signatures, flow details, and cell deformation. Next, we employed a compound droplet model consisting of an outer cell membrane, cytoplasm and the nucleus to study the flow dynamics more realistically. The effects of different parameters such as the nuclear to cytoplasmic size ratio (N/C), operating flow rate and viscosity of the cell has been investigated. We studied critical pressure for the CTC at different flow rates as it plays a crucial role in the device operation in ensuring a successful passing event. Our study provides an insight into the cell squeezing process and its characteristics, which can guide in the design and optimization of next-generation deformation-based CTC microfilters.
Author: Christopher Michael Landry
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages :
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Book Description
Throughout the world, cancer is a primary health concern due its high mortality rate. The typical cause of death from cancer is metastasis, which is the spreading of a primary tumor to distant organs. Currently, cancer metastasis is attributed to Circulating Tumor Cells (CTCs). A CTC is a cancer cell that has dislodged from the primary tumor and entered the blood stream. In order to achieve early cancer detection and improve patient prognosis, CTCs must be separated from whole blood samples. One of the most promising ways to achieve this separation is through microfluidic devices. Unfortunately, experimental testing of microfluidic devices is expensive, time-consuming, and lacks the ability to demonstrate underlying physics. To help resolve the issues associated with experimental testing, numerical modeling is employed. Here, two types of label-free microfluidic devices are modeled and tested. First, a microfiltration device is modeled and the effects of a non-axisymmetric approach are tested. From the results, critical pressure was found to be a robust design criterion for microfiltration devices regardless of CTC approach condition. CTC transit time on the other hand was determined to have a dependence on approach condition; therefore, should not be used in designing microfiltration devices. The other type of label-free microfiltration device tested was a Deterministic Lateral Displacement (DLD) device. Here, underlying causes of experimental observations for a symmetric airfoil shaped pillar design were achieved through numerical modeling of flow fields and array anisotropy. Results show that array anisotropy is responsible for creating a lateral shift in the flow field. Critical size of the DLD device is reduced when the flow field shifts toward the direction of bumped motion, and increases when shifting occurs away from bumped motion. Additionally, an equation is proposed that relates migration angle to anisotropy via pseudoperiodicity. Lastly, a working limit for symmetric airfoil shaped pillar DLD devices was found to be between -25° and -35° angle of attack. These findings will aid in future design work and open the possibility of new applications for micro fabricated DLD devices by achieving smaller critical sizes than previously possible.
Author: James Paul Smith
Publisher:
ISBN:
Category :
Languages : en
Pages : 139
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Book Description
The capture of rare cells from complex fluids, such as circulating tumor cells (CTCs) from a peripheral blood sample, has the potential to significantly advance our understanding and treatment of disease. Here, we consider microfluidic devices designed to isolate rare cells by bringing them into contact with, and binding the cells to, an antibody-functionalized obstacle array geometry. Each downstream biomedical assay, such as single-cell genetic analyses or enumeration for the monitoring of disease progression, requires a different balance of capture efficiency and sample purity in isolating the rare cells; this work addresses that need for application-specific microfluidic device geometries by presenting a series of numerical simulations for design optimization. We have developed coupled computational fluid dynamics, particle advection, and cell adhesion Monte Carlo simulations that predicts the probability of capturing target and contaminating cells in a given device geometry, and have applied these simulations to the study the capture of prostate and pancreatic cancer cells. We expand these simulations to consider the effect of dielectrophoresis (DEP), and show that it is possible to apply DEP forcing within the obstacle array to simultaneously increase the capture of target pancreatic cancer cells (using positive DEP) and decrease the capture of contaminating cells (using negative DEP). Finally, we present a transfer function approximation of cell transport in obstacle arrays, and apply that approximation to study the effects of reversing arrays and off-design boundary conditions. This work advances our understanding of rare cell immunocapture in microfluidic obstacle arrays, lays the groundwork for the experimental study of DEP-immunocapture devices, and presents an engineering framework to identify optimized geometries for each unique rare cell capture application.
Author: Chao Jin
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Z. Hugh Fan
Publisher: John Wiley & Sons
ISBN: 1118915534
Category : Science
Languages : en
Pages : 479
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Book Description
Introduces the reader to Circulating Tumor Cells (CTCs), their isolation method and analysis, and commercially available platforms Presents the historical perspective and the overview of the field of circulating tumor cells (CTCs) Discusses the state-of-art methods for CTC isolation, ranging from the macro- to micro-scale, from positive concentration to negative depletion, and from biological-property-enabled to physical-property-based approaches Details commercially available CTC platforms Describes post-isolation analysis and clinical translation Provides a glossary of scientific terms related to CTCs
Author: David Caballero
Publisher: Springer Nature
ISBN: 3031040392
Category : Medical
Languages : en
Pages : 599
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Book Description
This book offers a comprehensive overview of the development and application of microfluidics and biosensors in cancer research, in particular, their applications in cancer modeling and theranostics. Over the last decades, considerable effort has been made to develop new technologies to improve the diagnosis and treatment of cancer. Microfluidics has proven to be a powerful tool for manipulating biological fluids with high precision and efficiency and has already been adopted by the pharmaceutical and biotechnology industries. With recent technological advances, particularly biosensors, microfluidic devices have increased their usefulness and importance in oncology and cancer research. The aim of this book is to bring together in a single volume all the knowledge and expertise required for the development and application of microfluidic systems and biosensors in cancer modeling and theranostics. It begins with a detailed introduction to the fundamental aspects of tumor biology, cancer biomarkers, biosensors and microfluidics. With this knowledge in mind, the following sections highlight important advances in developing and applying biosensors and microfluidic devices in cancer research at universities and in the industry. Strategies for identifying and evaluating potent disease biomarkers and developing biosensors and microfluidic devices for their detection are discussed in detail. Finally, the transfer of these technologies into the clinical environment for the diagnosis and treatment of cancer patients will be highlighted. By combining the recent advances made in the development and application of microfluidics and biosensors in cancer research in academia and clinics, this book will be useful literature for readers from a variety of backgrounds. It offers new visions of how this technology can influence daily life in hospitals and companies, improving research methodologies and the prognosis of cancer patients.
