Download or read book Microfluidic Platform for Capturing Circulating Tumor Cells from Whole Blood written by Sweta Gupta and published by . This book was released on 2011 with total page 48 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Isolation and Enrichment of Circulating Tumor Cells from Human Peripheral Blood Using a Chip Disc Microfluidic Platform written by 徐韋凡 and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book A Microfluidic Device for Capturing Circulating Tumor Cells written by Nika Nikbakht and published by . This book was released on 2015 with total page 67 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Circulating Tumor Cells written by Z. Hugh Fan and published by John Wiley & Sons. This book was released on 2016-03-25 with total page 505 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Microfluidic Systems for Cancer Diagnosis written by Jose L. Garcia-Cordero and published by Springer Nature. This book was released on 2023-06-10 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed volume explores recent developments in microfluidics technologies for cancer diagnosis and monitoring. The book is divided into two sections that delve into techniques for liquid biopsy for cancer diagnosis and platforms for precision oncology or personalized medicine in order to create effective patient avatars for testing anti-cancer drugs. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Microfluidic Systems for Cancer Diagnosis serves as an ideal guide that will be helpful to either replicate the construction of microfluidic devices specifically developed for cancer diagnosis or to catalyze development of new and better cancer diagnostic devices.
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 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 PLATFORMS TOWARDS VIRUS DETECTION AND CANCER DIAGNOSIS BASED ON TUMOR CELLS written by Yiqiu Xia and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: As a major healthcare concern, highly pathogenic viral infection can spread globally with modern transportation. Viral infectious diseases have caused some of the deadliest pandemics and heavily damaged global economy in recorded human history. As we prepare for the next major emerging viral infectious disease outbreak, there is an urgent need for the development of new techniques that can rapidly detect viruses and perform surveillance of viral infectious diseases at any location. On the other and, cancer is a major disease in human society nowadays, leading to the second most deaths worldwide. Circulating tumor cell (CTC) has been established as a liquid biopsy marker, however, there are demands of fast and accurate CTC detection. Microfluidics has the advantages of high throughput, high sensitivity, accurate flow rate control and low cost, allowing it well suited for virus and cancer diagnosis. Besides, the geometry of microfluidics allows precisely controlling of the physical, chemical, biological, and physiological environment at the cellular level or even at the molecular level for fundamental studies of cancers.My major works can be classified into two categories, microfluidic devices for virus diagnosis and microfluidic platforms towards cancer diagnosis. For the virus diagnosis, one microfluidic device for size-based virus isolation and another one for immunoaffinity-based virus detection are developed, respectively. In the first device, inter-wire size-tunable porous silicon nanowire forest is embedded inside the microfluidic channel to trap avian influenza viruses based on their size and then release trapped viruses by nanowire degradation. About 50% of virus can be captured and 60% of trapped virus can be released for culture and further analysis. In the second device, immunoassay is employed inside the channels to capture and detect virus in only ~1.5 hours. Colorimetric reaction with gold nanoparticles and silver enhancer allow detection with naked eyes with about one order of magnitude better than conventional fluorescent enzyme-linked immunosorbent assay (ELISA). Simply by introducing an optical detection scheme with a smartphone detection system, the sensitivity can be 30 times better than conventional fluorescent ELISA. Two microfluidic platforms were developed toward cancer diagnosis. The first microfluidic platform aims to study the process of CTC size-based microfiltration and cancer cell translocating through micro constrictions by mimicking the microfiltration process and in vivo micro-constrictions inside a microfluidic device. It is found that the deformability and size of nucleus instead of the whole cell dominate cellular translocation through micro constrictions under the normal physiological pressure range used by CTC microfiltration. The result is consistent with the size-based enrichment of white blood cells and CTCs from peripheral blood of metastatic cancer patients using a CTC microfilter previously developed in my group. It indicates that the size and deformability of cell nucleus play a critical role in CTC size-based microfiltration and potentially cancer cell translocating micro constrictions in vivo. The second microfluidic platform can measure the Youngs modulus of cells in a high throughput fashion by applying a micropipette aspiration model in an array of micro constrictions. Using this device, a subtype of cancer cells with a softer mechanical phenotype can be enriched. This subtype of cancer cells shows enhanced invasive-related properties and can be used for further study of metastasis and cancer cell heterogeneity.
Download or read book Capture and Analysis of Circulating Tumor Cells in Microfluidics written by Julien Autebert 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 Isolation of Metastatic Cancer Cells from Whole Blood in a Centrifugal Microfluidic Platform Via Density Gradient written by 連偉豪 and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 A MICROFLUIDIC PLATFORM INTEGRATED WITH FIELD EFFECT TRANSISTORS FOR DETECTION OF CIRCULATING TUMOR CELLS written by Yi-Hong Chen and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Proteomic Profiling written by Anton Posch and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Microfluidic Analysis of Metastatic Cancer Biomarkers written by Steven Michael Santana and published by . This book was released on 2014 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is the second-leading cause of death in the United States. Metastasis is responsible for 90% of cancer-related death and progresses through multifarious, poorly-understood cascades as they are difficult to observe in vivo. It is widely held that deciphering the metastatic cascade and identifying metastatic precursors will lead to improved patient outcomes. In this work, we isolate and study cancer biomarkers, specifically circulating tumor cells (CTCs) and cancer-cell-derived extracellular shed vesicles (ESVs), implicated in cancer progression and metastasis. First we describe the design, fabrication, and use of a Hele-Shaw microfluidic system to optimize rarecell immunocapture parameters with a focus on informing the design of systems for CTC isolation from patient whole blood. Our study includes the role of antibody selection, density, antigen locations, and multi-modal capture surfaces, as well as shear stress, on rare cell capture. We use LNCaPs, a PSMA-expressing prostate cancer cell line, as a model for CTCs and anti-PSMA antibodies, J591 and J415, to inform chemistry-mediated immobilization. Next, we focus on another cancer-disseminated marker, extracellular shed vesicles. ESVs, including exosomes and cancer-cell-derived microvesicles, are disseminated throughout the body and represent an important conduit of cell communication. Microvesicles have potential as a cancer biomarker as they are believed to transform tumor microenvironments and prime the metastatic niche. Cancercell-derived ESV subpopulations consist of a small-diameter exosome population and a large-diameter, cancer-cell-specific microvesicle population, each formed by unique mechanisms. It is believed that size correlates with biological properties of interest, but isolating these subpopulations, to discern chemical, biological, or physical differences, is challenging. We designed a deterministic lateral displacement microfluidic platform to isolate a pure microvesicle sample from the heterogeneous cancer-cell-derived ESV population. The threshold diameter differentiating the microvesicle population from the exosome population was determined by characterizing the size distributions of ESVs harvested from multiple cancer cell lines of breast, brain, and pancreas origin. Our microvesicle-isolation microfluidic technology facilitates future investigations regarding microvesicles' role in cancer progression by enabling identification of cargo carried by the microvesicle subpopulation.
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 Microfluidic Platform to Create Micro Vortices to Enhance the Capture Cancer Stem Cells written by and published by . This book was released on 2018 with total page 52 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer Stem Cells (CSCs) are tumorigenic cells that have characteristics similar to normal stem cells but have ability to generate cells, which are found in the cancer sample. The rare amount of CSC cells in the whole blood makes isolating them from other cells a daunting task. Well defined phenotypes of different CSCs makes immunocapturing technique of CSCs more desirable. A microfluidic device is a proven platform for user constrained microenvironments which can be optimized by small scale volumetric flow experimentation. In this study, we showed a micromixer design (Staggered herringbones) can be optimized to get the maximum chaotic mixing within antibody coated on the microchannels to further capture CSCs. Our device’s design includes the configuration of Staggered Herringbones on top and bottom of the channels (Staggered High Low Herringbones- SHiLoH). It was constructed using polydimethylsiloxane (PDMS) foundation and thinly coated with an alginate hydrogel derivatized with streptavidin. We also compared between the Single walled Staggered Herringbones device and the Staggered High Low Herringbones device with different orientation of the herringbones. The results showed that the micro vortex generated within the micro channels of Staggered High Low design makes the device more efficient than the Single walled staggered Herringbones. Further the non-stickiness of alginate and antigen-specific antibodies can allow better target-specific cell isolation. Our qualitative and quantitative results demonstrate the advancements in cancer stem cell isolation and more comprehensive single-cell and cluster analysis.
Download or read book Design Fabrication and Evaluation of Multiple Microfluidic Model Devices for Enrichment of Circulating Tumour Cells from Whole Blood written by Simon de Regt and published by . This book was released on 2018 with total page 71 pages. Available in PDF, EPUB and Kindle. Book excerpt: