Separation of Circulating Tumor Cells Using Deformation-based Microfluidic Devices PDF Download
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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: 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: Xiaolong Zhang
Publisher:
ISBN:
Category : Mechanical engineering
Languages : en
Pages :
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Book Description
Author: Yuting Zhou
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Deformation-based cell separation has emerged recently as an effective approach to isolate cells that have similar size but different deformability and thus exhibits potential applications in disease diagnostic including circulating cancer cells and sickle cell anemia. However, key physical parameters that regulate deformation-based cell separation remain unclear. Here we developed a microfluidic approach in a droplet-based model system to explore the effect of physical parameters of droplets including size, viscosity, and velocity on deformation-based separation. We fabricated microfluidic devices that had a straight flow-focusing channel, a cylindrical post, two inlets and three outlets and studied droplet sorting at different channel dimensions and flow rate. We showed that decreasing viscosity or increasing velocity of droplets would result in decreasing the effective size of droplets in droplet sorting. The results showed that droplets with a large size or high viscosity were sorted to side outlets at low velocity in the microfluidic device whereas droplets with a small size or low viscosity exited through the center outlet at high velocity. Such separation was determined by the characteristic distance ([delta]) and impact angle ([theta]) during a two-step sequential droplet deformation process. The droplets were sorted to the side outlets when [delta] ≥ 0.542 or [theta] ≥ 28°, and the droplet exited through the center outlet when [delta] ≤ 0.525 or [theta] ≤ 28°. We then further tested the dependence of [delta] and [theta] on cell sorting using RPF-HUVECs and showed that with cells up to the characteristic distance [delta] = 0.419 tested in the experiment, all exited through the center outlet. [theta] measurement was skipped for all the cells exiting through the center outlet because it was not applicable. Future studies of the role of [delta] and [theta] in cell sorting however is needed by optimizing the geometric parameters of the microfluidic device, i.e., gap distance, channel width, post diameter. With properly designed microfluidic device, this microfluidic approach is expected to provide a way for conducting fast, low-cost, and efficient cell analysis that would benefit future disease diagnostics.
Author: Chao Jin
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Arian Aghilinejad
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Takasi Nisisako
Publisher: MDPI
ISBN: 3039366947
Category : Technology & Engineering
Languages : en
Pages : 230
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Book Description
Microfluidic platforms are increasingly being used for separating a wide variety of particles based on their physical and chemical properties. In the past two decades, many practical applications have been found in chemical and biological sciences, including single cell analysis, clinical diagnostics, regenerative medicine, nanomaterials synthesis, environmental monitoring, etc. In this Special Issue, we invited contributions to report state-of-the art developments in the fields of micro- and nanofluidic separation, fractionation, sorting, and purification of all classes of particles, including, but not limited to, active devices using electric, magnetic, optical, and acoustic forces; passive devices using geometries and hydrodynamic effects at the micro/nanoscale; confined and open platforms; label-based and label-free technology; and separation of bioparticles (including blood cells), circulating tumor cells, live/dead cells, exosomes, DNA, and non-bioparticles, including polymeric or inorganic micro- and nanoparticles, droplets, bubbles, etc. Practical devices that demonstrate capabilities to solve real-world problems were of particular interest.
Author: Catherine Alix-Panabieres
Publisher: MDPI
ISBN: 3039286986
Category : Science
Languages : en
Pages : 366
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Book Description
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.
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.
Author: Z. Hugh Fan
Publisher: John Wiley & Sons
ISBN: 1119244544
Category : Science
Languages : en
Pages : 505
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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: 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.
