Microfluidic Platform for Capturing Circulating Tumor Cells from Whole Blood

Microfluidic Platform for Capturing Circulating Tumor Cells from Whole Blood PDF 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.

A Microfluidic Device for Capturing Circulating Tumor Cells

A Microfluidic Device for Capturing Circulating Tumor Cells PDF 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.

Isolation and Enrichment of Circulating Tumor Cells from Human Peripheral Blood Using a Chip Disc Microfluidic Platform

Isolation and Enrichment of Circulating Tumor Cells from Human Peripheral Blood Using a Chip Disc Microfluidic Platform PDF Author: 徐韋凡
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Circulating Tumor Cells

Circulating Tumor Cells PDF 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

Microfluidic Systems for in Situ Molecular Characterization of Circulating Tumor Cells

Microfluidic Systems for in Situ Molecular Characterization of Circulating Tumor Cells PDF Author: Karla Perez Toralla
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Microfluidic Systems for Cancer Diagnosis

Microfluidic Systems for Cancer Diagnosis PDF Author: Jose L. Garcia-Cordero
Publisher: Springer Nature
ISBN: 107163271X
Category : Medical
Languages : en
Pages : 327

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Book Description
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.

Immunomagnetic Microfluidic Screening System for Circulating Tumor Cells Detection and Analysis

Immunomagnetic Microfluidic Screening System for Circulating Tumor Cells Detection and Analysis PDF Author: Yu-Yen Huang
Publisher:
ISBN:
Category :
Languages : en
Pages : 216

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Book Description
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.

MICROFLUIDIC PLATFORMS TOWARDS VIRUS DETECTION AND CANCER DIAGNOSIS BASED ON TUMOR CELLS.

MICROFLUIDIC PLATFORMS TOWARDS VIRUS DETECTION AND CANCER DIAGNOSIS BASED ON TUMOR CELLS. PDF Author: Yiqiu Xia
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
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.

Capture and Analysis of Circulating Tumor Cells in Microfluidics

Capture and Analysis of Circulating Tumor Cells in Microfluidics PDF Author: Julien Autebert
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Microfluidics Diagnostics

Microfluidics Diagnostics PDF Author: Valérie Taly
Publisher: Springer Nature
ISBN: 1071638505
Category :
Languages : en
Pages : 254

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Book Description