Download or read book Isolation Detection and Functional Characterization of Circulating Tumor Cells Using Microfluidic based Technologies written by Leyla Kermanshah and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Primary tumors shed thousands of cells into blood circulation every day. These circulating tumor cells (CTCs) play a key role in metastasis. The application of CTCs, regarded as a real-time, non-invasive and cost-effective "liquid biopsy", has drawn much attention in the last two decades. However, their application in clinical practice has been limited due to their extreme rarity and heterogeneity. Highly specialized technologies have been developed to address these challenges. So far, the majority of technologies have focused on separating CTCs from a background of millions of blood cells with high purity and sensitivity. Despite the technological advancement in CTC enrichment, the clinical relevance of these cells is still controversial. In-depth characterization is therefore needed to elucidate their functionality in the metastatic cascade. The principal aim of this thesis is to characterize heterogeneous populations of CTCs, sorting them into subpopulations and assessing the CTCs for aggressive phenotypes. In this thesis, specialized microfluidic-based technologies are used for isolating CTCs and profiling their phenotypes according to a surface marker expression. We describe a two-dimensional separation approach that separates phenotypically-distinct subpopulations of cancer cells. Profiling CTCs based on an epithelial marker enabled us to identify CTCs that have undergone the epithelial to mesenchymal transition (EMT). The EMT-transformed cells exhibited greater invasive phenotypes, as confirmed by an in vitro collagen uptake assay. Using magnetic ranking cytometry (MagRC), a new technology designed for profiling rare cells, we successfully obtained phenotypic profiles from cancer cells and xenograft CTCs. To investigate metastatic phenotypes of CTCs, CTCs from mice bearing prostate cancer xenografts with different levels of aggressiveness were analysed by MagRC. Real-time monitoring of dynamic changes in CTC phenotypes during cancer progression and a course of chemotherapy gave us insights into tumor evolution and treatment efficiency. Metastatic xenografts showed a heterogeneous population of CTCs with epithelial-mesenchymal plasticity. A decrease in heterogeneity followed by a reduction in metastasis incidence was observed after a course of chemotherapy administered to highly metastatic xenografts. Phenotypic profiling of CTCs can potentially be used for cancer prognostic profiling and therapeutic selection.
Download or read book Isolation Characterization and Expansion of Heterogeneous Circulating Tumor Cell CTC Populations from Cancer Patients Using Microfluidic Technologies written by Mina Zeinali and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Rapid Isolation and Biophysical Characterization of Circulating Tumor Cells with Microfluidic Vortex Technology written by James Che and published by . This book was released on 2015 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt: Disseminated and circulating tumor cells are key players of metastatic cancer and have high diagnostic and prognostic value. These cells may often accumulate and persist in body fluids--such as in pleural effusions or blood--which are minimally-invasive sources for patient sampling. However, tumor cells are relatively scarce and must typically be enriched from a large background of blood cells. An inertial microfluidic device was developed to specifically trap and concentrate large tumor cells in stable microvortices which form under high flow rates. The novel label-free Vortex platform was optimized to isolate large rare cells at high efficiency (up to 80%), purity (10-80%), concentration (~200 L volume), and viability (>80%) in a short time period (
Download or read book Technologies for the Isolation of Circulating Tumor Cells written by Ajay Mukesh Shah and published by . This book was released on 2012 with total page 129 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastasis, the spread and growth of tumor cells from the primary site to distant organs, is arguably the most devastating and deadly attribute of cancer, and is ultimately responsible for 90% of cancer-related deaths. Circulating tumor cells (CTCs) are exceedingly rare cells found in the whole blood of cancer patients which have the potential to serve as a 'blood biopsy'. The intricate characterization of these cells could result in an entire new class of therapies directly targeting metastasis. Present technologies enable only a susbset of potential analyses to be conducted, principally due to sub-optimal cell isolation sensitivity, purity, throughput, or handling method. Here, we present two novel technologies to address the challenge of CTC isolation. First, we build on affinity-based microfluidic cell capture platforms by developing sacrificial hydrogel coatings to enable the innocuous release of captured cells; we demonstrate that model CTCs captured from whole blood remain viable and proliferative following release and are compatible with downstream immunostaining and FISH analysis. Second, we present a novel cell sorting system that interrogates over 10 million individual events each second, resulting in a high throughput, ultra-efficient rare cell sorter that delivers enriched cells in a vial, readily compatible with virtually any downstream assay. This is the first system combining the high sensitivity and single cell resolution that is characteristic of FACS with the practicality of MACS at a throughput and specificity afforded by inertial focusing, enabling operation in both 'positive selection' and 'negative depletion' modes. We find greater than 90% cell isolation efficiencies with over 2.5 log depletion of contaminating WBCs. Furthermore, the system is applied to clinical patient samples, and proof-of-concept is demonstrated in a cohort of breast, lung and prostate patients. Working in a negative depletion mode to isolate target cells in an unbiased fashion, we used the system to assess single putative CTCs isolated from an endogenous pancreatic mouse model for gene expression of tumor markers. Initial data confirms CTC heterogeneity at the single cell level, and positions us to move forward with single cell transcriptome sequencing, which may reveal a broad array of CTC phenotypes including metastatic precursors.
Download or read book Circulating Tumor Cells in Breast Cancer Metastatic Disease written by Roberto Piñeiro and published by Springer Nature. This book was released on 2020-04-17 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is aimed to summarise the key aspects of the role of circulating tumour cells (CTCs) in breast cancer, with special attention to their contribution to tumour progression and establishment of metastatic disease. We aim to give a clear overview of the knowledge about CTCs, framed in the context of breast cancer, by analysing basic and clinical research carried out so far. In a broader sense, we will address what are the main clinical needs of this disease based on its molecular heterogeneity (subtypes) and lay out the knowledge and understanding that CTCs are giving about it and how they are contributing and can still improve the better monitoring and management of breast cancer patients. We will discuss the evidences of the use of CTCs as a tool to monitor cancer progression and therapy response, based on the prognostic and predictive value they have, as well as a tool to unravel mechanisms of resistance to therapy and to identify new biomarkers allowing to predict therapy success. Moreover, we will analyse the main aspects of ongoing clinical trials and how they can contribute to determine the clinical utility of CTCs as a breast cancer biomarker. We will also touch upon general knowledge or basic notions of the biology of the metastatic process in epithelial cancers, in order to understand the origin and biology of CTCs. In this sense, we will pay special attention to EMT (epithelial to mesenchymal transition), dormancy and minimal residual disease, three key aspects that determine the outcome of the disease. We will also cover general aspects on the isolation and characterization techniques applies to the study of CTCs, and also the possibilities that the study of CTCs, as a biomarker with biological function, is opening in terms of understanding the biology of metastatic cells and the identification of therapeutic targets based on the functional and molecular characterization of CTCs. Lastly, we will try to foresee the future of CTCs in terms of clinical application and implementation in the clinical routine.
Download or read book Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer written by Michail Ignatiadis and published by Springer Science & Business Media. This book was released on 2012-04-23 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: This important book provides up-to-date information on a series of topical issues relating to the approach to minimal residual disease in breast cancer patients. It first explains how the study of minimal residual disease and circulating and disseminated tumor cells (CTCs/DTCs) can assist in the understanding of breast cancer metastasis. A series of chapters then discuss the various technologies available for the detection and characterization of CTCs and DTCs, pinpointing their merits and limitations. Detailed consideration is given to the relevance of CTCs and DTCs, and their detection, to clinical research and practice. The role of other blood-based biomarkers is also addressed, and the closing chapters debate the challenges facing drug and biomarker co-development and the use of CTCs for companion diagnostic development. This book will be of interest and assistance to all who are engaged in the modern management of breast cancer.
Download or read book Development of a Microfluidic Flow Cytometry Platform with Fluorescence and Light Scattering Detection for the Rapid Characterization of Circulating Tumor Cells written by Samantha Ann Stewart-James and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Circulating tumor cells (CTCs) have become a key component in the identification and treatment of cancer. Once dislodged from the main tumor, CTCs travel through the bloodstream and cause metastasis. Early detection and identification of these cells can help in the evaluation and prognosis of various types of cancer, as well as assisting in patient treatments by determining the spread of the disease. Here, a high-throughput microfluidic analysis technique is described that can efficiently detect and identify cells, with the specific identification of CTCs as a future application through fluorescent labeling in mind. As proof of principle, the device has been shown to detect and characterize individual human Jurkat (T-lymphocyte) cells at a rate of 100 cells/minute. The device employs micro-scale flow focusing to isolate individual cells. The cells are detected using both light scattering and laser-induced fluorescence to evaluate cell size and surface functionality.
Download or read book Circulating Tumor Cells From Biotech Innovation to Clinical Utility Part A written by and published by Elsevier. This book was released on 2023-09-21 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Circulating Tumor Cells, from biotech innovation to clinical utility" provides an overview of the most recent technological and clinical advances with regards to the study of circulating tumor cells (CTCs) in solid tumors. The volumes cover studies on CTCs in breast, prostate, colorectal and lung cancer, with a focus on clinical utility, and also include methodological and biological topics such as CTC culture, multi-omic characterization of CTCs, atypical CTC populations and interaction between CTCs and immunity. Provide a summary of the latest advances of CTC studies in the most common solid tumors Give an overview of the most advanced methods for CTC characterization and functional analysis Present new perspective on the clinical utility of CTCs
Download or read book Microfluidics for Functional Analysis of Circulating Tumor Cells written by Lucas Armbrecht and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Tumor Organoids written by Shay Soker and published by Humana Press. This book was released on 2017-10-20 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Download or read book Immunomagnetic Microfluidic Screening System for Circulating Tumor Cells Detection and Analysis written by Yu-Yen Huang and published by . This book was released on 2013 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: Circulating tumor cells (CTCs) are known to escape from the primary tumor site and may settle down at the distant organ to grow a second tumor. CTCs are one of causes initiating carcinoma metastasis. Detection of CTCs has been considered to be valuable for cancer management, including diagnosis, prognosis, and clinical treatment management. However, efficient isolation, enumeration, characterization, and genetic analysis of CTCs in whole-blood samples from cancer patients are very challenging due to their extremely low concentration and rare nature (per CTC in blood cells is 1:106-109). With the increasing worldwide death rate associated with cancer, there is a desperate demand for a high-sensitivity, high-throughput, and low-cost detection and separation system. My doctoral research focused on the design and fabrications of the screening system for the detection of CTCs with further analysis of captured CTCs, such as immunofluoresce staining and fluorescence in-situ hybridization (FISH). The distinct significance of this research is that the development of the computer-controlled rotational holder with a series of six inverted microfluidic chips reduced the cost by significantly reducing the consumption of magnetic carriers (25% of the consumed amount used in the commercial CellSearch® system), increasing the capture efficiency by manipulating the blood sedimentation in the microchannel, enhancing the system stability by integrating the micromagnets on the plain glass slide substrate, and achieving high throughput because of the high flow rate (2.5 mL/hr) and large screening volume (screening up to six chips in parallel with each containing 2.5 mL of blood). Immunofluorescence staining and the FISH method have been performed to prove the capability of the system. In addition, the system has been successfully applied for patient samples screening. The incorporation of micromagnets has demonstrated that micromagnets provide localized magnetic forces to scatter the target cancer cells and free nanoparticles throughout the whole channel substrate to increase the channel space usage by 13%. Four cancer cell lines, including COLO 205 (colorectal cancer), SK-BR-3 (breast cancer), MCF-7 (breast cancer), and PC3 (prostate cancer), were spiked in blood samples from healthy donors to verify high capture efficiency of the developed system. On average, over a 97% capture rate was demonstrated for all cell lines. Moreover, the developed screening system has been successfully screened over 40 patient samples, including metastatic lung cancer, breast cancer, prostate cancer, and colorectal cancer. After capture of CTCs, immunofluorescence staining was used to identified the captured cancer cells and the FISH method was performed to characterize the isolated cancer cells by studying the gene expression of CTCs from breast cancer. The proposed automated immunomagnetic microchip-based screening system shows high capture efficiency (average 97% for three spiked cell lines), high throughput (15 mL of blood sample per screening), high sensitivity, high specificity, and low nanoparticle consumption (75% less than CellSearch® system). The screening system provides great promise as a clinical tool for early cancer diagnosis, diagnosis, personalized therapy, and treatment monitoring.
Download or read book Microfluidic Device Design for Capturing Circulating Tumor Cells written by Shrutilaya Karunanidhi and published by . This book was released on 2013 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Antibody free Isolation of Circulating Tumor Cells by Dielectrophoretic Field low Fractionation written by Sangjo Shim and published by . This book was released on 2013 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work focuses on the integration of microfluidics and dielectrophoresis(DEP) with the principles of field flow fractionation (FFF) to create a continuous-flow isolator for rare and viable circulating tumor cells (CTCs) from peripheral blood mononuclear cells (PBMNs) drawn from cancer patients. The method exploits differences in the plasma membrane capacitances of tumor and blood cells, which correspond to differences in the membrane surface areas of these cell types. DEP-FFF was first adapted to measure cell membrane capacitance, cell density and deformability profiles of cell populations. These properties of the NCI-60 panel of cancer cell types, which represents the wide functional diversity of cancers from 9 organs and leukemia, were compared with the normal cell subpopulations of peripheral blood. In every case, the NCI-60 cells exhibited membrane capacitance characteristics that were distinct from blood and, as a result, they could be isolated from blood by DEP. The heightened cancer cell membrane capacitances correlated strongly with membrane-rich morphological characteristics at their growth sites, including cell flattening, dendritic projections, and surface wrinkling. Following harvest from culture and maintenance in suspension, cancer cells were found to shed cytoplasm and membrane area over time and the suspended cell populations developed considerable morphological diversity. The shedding changed the cancer cell DEP properties but they could still be isolated from blood cells. A similar shedding process in the peripheral blood could account for the surprisingly wide morphological diversity seen among circulating cells isolated from clinical specimens. A continuous flow DEP-FFF method was devised to exploit these findings by allowing CTCs to be isolated from the nucleated cells of 10 mL clinical blood specimens in 40 minutes, an extremely high throughput rate for a microfluidic-based method. Cultured cancer cells could be isolated at 70-80% efficiency using this approach and the isolation of CTCs from clinical specimens was demonstrated. The results showed that the continuous DEP-FFF method delivers unmodified, viable CTCs for analysis, is perhaps universally applicable to isolation of CTCs from different cancer types and is independent of surface antigens - making it suitable for cells lacking the epithelial markers used in currently accepted CTC isolation methods.
Download or read book Microfluidic Systems for in Situ Molecular Characterization of Circulating Tumor Cells written by Karla Perez Toralla and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nanomaterials For Energy Conversion And Storage written by Dunwei Wang and published by World Scientific. This book was released on 2017-11-10 with total page 836 pages. Available in PDF, EPUB and Kindle. Book excerpt: The use of nanomaterials in energy conversion and storage represents an opportunity to improve the performance, density and ease of transportation in renewable resources. This book looks at the most recent research on the topic, with particular focus on artificial photosynthesis and lithium-ion batteries as the most promising technologies to date. Research on the broad subject of energy conversion and storage calls for expertise from a wide range of backgrounds, from the most fundamental perspectives of the key catalytic processes at the molecular level to device scale engineering and optimization. Although the nature of the processes dictates that electrochemistry is a primary characterization tool, due attention is given to advanced techniques such as synchrotron studies in operando. These studies look at the gap between the performance of current technology and what is needed for the future, for example how to improve on the lithium-ion battery and to go beyond its capabilities.Suitable for students and practitioners in the chemical, electrochemical, and environmental sciences, Nanomaterials for Energy Conversion and Storage provides the information needed to find scalable, economically viable and safe solutions for sustainable energy.
Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
Download or read book Circulating Tumor Cells written by Catherine Alix-Panabieres and published by MDPI. This book was released on 2020-04-03 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: The analysis of circulating tumor cells (CTCs) as a real-time liquid biopsy approach can be used to obtain new insights into metastasis biology, and as companion diagnostics to improve the stratification of therapies and to obtain insights into the therapy-induced selection of cancer cells. In this book, we will cover all the different facets of CTCs to assemble a huge corpus of knowledge on cancer dissemination: technologies for their enrichment, detection, and characterization; their analysis at the single-cell level; their journey as CTC microemboli; their clinical relevance; their biology with the epithelial-to-mesenchymal transition (EMT); their stem-cell properties; their potential to initiate metastasis at distant sites; their ex vivo expansion; and their escape from the immune system.
