scholarly journals Design of a Hybrid Inertial and Magnetophoretic Microfluidic Device for CTCs Separation from Blood

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 877
Author(s):  
Rohollah Nasiri ◽  
Amir Shamloo ◽  
Javad Akbari
Keyword(s):  
Blood Sample ◽  
Cell Separation ◽  
Soft Lithography ◽  
Permanent Magnets ◽  
Fluid Dynamic ◽  
Magnetic Method ◽  
Single Chip ◽  
Particle Trajectories ◽  
Inertial Method ◽  
Separation Unit

Circulating tumor cells (CTCs) isolation from a blood sample plays an important role in cancer diagnosis and treatment. Microfluidics offers a great potential for cancer cell separation from the blood. Among the microfluidic-based methods for CTC separation, the inertial method as a passive method and magnetic method as an active method are two efficient well-established methods. Here, we investigated the combination of these two methods to separate CTCs from a blood sample in a single chip. Firstly, numerical simulations were performed to analyze the fluid flow within the proposed channel, and the particle trajectories within the inertial cell separation unit were investigated to determine/predict the particle trajectories within the inertial channel in the presence of fluid dynamic forces. Then, the designed device was fabricated using the soft-lithography technique. Later, the CTCs were conjugated with magnetic nanoparticles and Ep-CAM antibodies to improve the magnetic susceptibility of the cells in the presence of a magnetic field by using neodymium permanent magnets of 0.51 T. A diluted blood sample containing nanoparticle-conjugated CTCs was injected into the device at different flow rates to analyze its performance. It was found that the flow rate of 1000 µL/min resulted in the highest recovery rate and purity of ~95% and ~93% for CTCs, respectively.

Multiphase flow experiment and simulation for cells-on-a-chip devices

2019 ◽  
Vol 233 (4) ◽  
pp. 432-443 ◽  
Author(s):  
Meihua Zhang ◽  
Amy Zheng ◽  
Zhongquan C Zheng ◽  
Michael Zhuo Wang
Keyword(s):  
Multiphase Flow ◽  
Soft Lithography ◽  
Particle Deposition ◽  
Fluid Dynamic ◽  
Flow Behavior ◽  
Density Ratio ◽  
Simulation Method ◽  
Quantitative Agreement ◽  
Geometry Model

A microfluidic-based microscale cell-culture device, or a cells-on-a-chip device, provides a well-controlled environment with physiologically realistic factors that emulate the organ-to-organ network of human body. In the microsystem, the in vivo situation can be resembled closely by controlling the chip geometry model, medium flow behavior, medium-to-cell density ratio, and other fluid dynamic parameters. This study is to develop multiphase models to carry out experiments and simulate flow in such devices. A standard soft lithography method is used to build the three-dimensional microfluidic chips. A definitely good qualitative and reasonably good quantitative agreement is obtained between the experimental and simulation results for particle velocity in the microfluidic chip, which validates the numerical simulation method. The cell deposition rate influenced by the flow shear is studied. The influence of gravity, inlet velocity, and cell injection number on cell concentrations are also investigated. Comparisons of different designs of cells-on-a-chip devices are addressed in the study. The physics of flow dynamics and related cell particle motion due to each of the above-mentioned variables are discussed. The results show that the multiphase flow model is promising to be used for simulating cell particle deposition and concentration for the purpose of design of cells-on-a-chip devices.

Active High-Throughput Micromixer Using Injected Magnetic Mixture Underneath Microfluidic Channel

2020 ◽  
Author(s):  
Athira N. Surendran ◽  
Ran Zhou
Keyword(s):  
Soft Lithography ◽  
Permanent Magnets ◽  
Low Cost ◽  
Microfluidic Channel ◽  
Microfluidic Chips ◽  
Small Channel ◽  
Parametric Studies ◽  
Micro Level ◽  
Planar Location ◽  
Sample Dilution

Abstract Microfluidics has a lot of applications in fields ranging from pharmaceutical to energy, and one of the major applications is micromixers. A challenge faced by most micromixers is the difficulty in mixing within micro-size fluidic channels because of the domination of laminar flow in a small channel. Hence, magnetic field generated by permanent magnets and electromagnets have been widely used to mix ferrofluids with other sample fluids on a micro level. However, permanent magnets are bulky, and electromagnets produce harmful heat to biological samples; both properties are detrimental to a microfluidic chip’s performance. Taking these into consideration, this study proposes rapid mixing of ferrofluid using a two-layer microfluidic device with microfabricated magnet. Two microfluidic chips that consist of microchannels and micromagnets respectively are fabricated using a simple and low-cost soft lithography method. The custom-designed microscale magnet consists of an array of stripes and is bonded below the plane of the microchannel. The combination of the planar location and angle of the array of magnets allow the migration of ferrofluids, hence mixing it with buffer flow. Parametric studies are performed to ensure comprehensive understanding, including the angle of micro-scale magnets with respect to the fluidic channels, total flow rate and density of the array of magnets. The result from this study can be applied in chemical synthesis and pre-processing, sample dilution, or inducing reactions between samples and reagent.

scholarly journals Design and Simulation of an Integrated Centrifugal Microfluidic Device for CTCs Separation and Cell Lysis

Micromachines ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 699
Author(s):  
Rohollah Nasiri ◽  
Amir Shamloo ◽  
Javad Akbari ◽  
Peyton Tebon ◽  
Mehmet R. Dokmeci ◽  
...  
Keyword(s):  
Numerical Simulation ◽  
Angular Velocity ◽  
Microfluidic Device ◽  
Cell Separation ◽  
High Efficiency ◽  
Separation Efficiency ◽  
White Blood Cells ◽  
Cell Lysis ◽  
Target Cells ◽  
Separation Unit

Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprinting, and organs on a chip. Centrifugal microfluidic biochips created on compact disks show great potential in processing biological samples for point of care diagnostics. This study investigates the design and numerical simulation of an integrated microfluidic device, including a cell separation unit for isolating CTCs from a blood sample and a micromixer unit for cell lysis on a rotating disk platform. For this purpose, an inertial microfluidic device was designed for the separation of target cells by using contraction–expansion microchannel arrays. Additionally, a micromixer was incorporated to mix separated target cells with the cell lysis chemical reagent to dissolve their membranes to facilitate further assays. Our numerical simulation approach was validated for both cell separation and micromixer units and corroborates existing experimental results. In the first compartment of the proposed device (cell separation unit), several simulations were performed at different angular velocities from 500 rpm to 3000 rpm to find the optimum angular velocity for maximum separation efficiency. By using the proposed inertial separation approach, CTCs, were successfully separated from white blood cells (WBCs) with high efficiency (~90%) at an angular velocity of 2000 rpm. Furthermore, a serpentine channel with rectangular obstacles was designed to achieve a highly efficient micromixer unit with high mixing quality (~98%) for isolated CTCs lysis at 2000 rpm.

scholarly journals 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention

Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1060
Author(s):  
Anton Enders ◽  
John-Alexander Preuss ◽  
Janina Bahnemann
Keyword(s):  
Cell Separation ◽  
Separation Efficiency ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Optimal Operation ◽  
Dead Volume ◽  
Cell Retention ◽  
Separation Unit ◽  
Peristaltic Pumps ◽  
3D Printed

The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 106 cells mL−1. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use—thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation.

scholarly journals Micro–Macro: Selective Integration of Microfeatures Inside Low-Cost Macromolds for PDMS Microfluidics Fabrication

Micromachines ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 576 ◽  
Author(s):  
Edgar Jiménez-Díaz ◽  
Mariel Cano-Jorge ◽  
Diego Zamarrón-Hernández ◽  
Lucia Cabriales ◽  
Francisco Páez-Larios ◽  
...  
Keyword(s):  
Soft Lithography ◽  
Low Cost ◽  
Cost Effective ◽  
Microfluidic Chips ◽  
Single Chip ◽  
Lab On Chip ◽  
Molding Method ◽  
On Chip ◽  
Selective Integration ◽  
Important Progress

Microfluidics has become a very promising technology in recent years, due to its great potential to revolutionize life-science solutions. Generic microfabrication processes have been progressively made available to academic laboratories thanks to cost-effective soft-lithography techniques and enabled important progress in applications like lab-on-chip platforms using rapid- prototyping. However, micron-sized features are required in most designs, especially in biomimetic cell culture platforms, imposing elevated costs of production associated with lithography and limiting the use of such devices. In most cases, however, only a small portion of the structures require high-resolution and cost may be decreased. In this work, we present a replica-molding method separating the fabrication steps of low (macro) and high (micro) resolutions and then merging the two scales in a single chip. The method consists of fabricating the largest possible area in inexpensive macromolds using simple techniques such as plastics micromilling, laser microfabrication, or even by shrinking printed polystyrene sheets. The microfeatures were made on a separated mold or onto existing macromolds using photolithography or 2-photon lithography. By limiting the expensive area to the essential, the time and cost of fabrication can be reduced. Polydimethylsiloxane (PDMS) microfluidic chips were successfully fabricated from the constructed molds and tested to validate our micro–macro method.

scholarly journals The Effect of Magnet Structure on the Cogging Torque Reduction in a Permanent Magnet Generator

2021 ◽  
Vol 56 (1) ◽  
Author(s):  
Tajuddin Nur ◽  
Yudha Suherman ◽  
Herlina
Keyword(s):  
Permanent Magnet ◽  
Permanent Magnets ◽  
Magnetic Surface ◽  
Electric Machines ◽  
Magnetic Method ◽  
Cogging Torque ◽  
The Core ◽  
Initial Design ◽  
Simulation Results ◽  
Peak Value

The cogging torque would still be a constant part of permanent magnet-electric machines. This happens because of the construction in which permanent magnets are attached to the rotor, and a slot is present at the core of the stator. The contact between the two, related to the distance between the magnetic surface and the stator slot, makes it challenging to eliminate the cogging torque. This study aims to maximize cogging torque by reducing it with a new method. The proposed method is a mixture of two techniques that indicate significant promise. This invention mixes two techniques to improve the final results. The first process is called magnetic edge shaping, and the second technique is called a dummy slot on the stator. A fractional slot number (FSN) type with 24 slots and 18 poles is the permanent magnet machine used for this investigation. This work is assisted by software version 4.2 of the Finite Element Magnetic Method (FEMM), which will simulate the original and the proposed design. The proposed method proved to be effective in minimizing the peak value of the cogging torque, as shown by the simulation results of 98% of the initial design. Combining the two techniques may reduce the tangential value of the flux so that the flux leading to the slot is lower than the initial design.

Rapid Separation and Counting of Viable Microbial Cells in Food by Nonculture Method with Bioplorer, a Focusing-Free Microscopic Apparatus with a Novel Cell Separation Unit

2006 ◽  
Vol 69 (1) ◽  
pp. 170-176 ◽  
Author(s):  
TOMONORI SHIMAKITA ◽  
YOSHIKAZU TASHIRO ◽  
AKIRA KATSUYA ◽  
MIKAKO SAITO ◽  
HIDEAKI MATSUOKA
Keyword(s):  
Cell Separation ◽  
Practical Purpose ◽  
Membrane Filter ◽  
Culture Method ◽  
Rapid Separation ◽  
Separation Unit ◽  
Microbial Cells ◽  
Safety Control ◽  
Fluorescent Image ◽  
Highly Correlated

A nonculture method utilizing a novel apparatus, the bioplorer, was developed. The bioplorer is composed of an efficient cell separation unit, a focusing-free microscopic device, and an image analysis program. A meat or vegetable suspension is poured into the cell separation funnel, and insoluble matter in the sample suspension is trapped by prefilters. Microbial cells passing through the two prefilters are then trapped by the membrane filter (pore size, 0.4 μm). Trapped cells are double-stained with 4′,6′-diamidino-2-phenylindole and propidium iodide, and the membrane filter is removed and set on the focusing-free microscope. A fluorescent image is then recorded. Total numbers of viable and dead cells on the membrane filter can thus be determined automatically. One assay can be performed within 10 min, which is much faster than the culture method. The results obtained with both the nonculture method and the culture method for meat and vegetable samples were highly correlated (r = 0.953 to 0.998). This method is feasible for the practical purpose of food safety control.

One-step separation of CD20+cells from whole blood using bacterial magnetic particles displaying protein G

2008 ◽  
Vol 1094 ◽  
Author(s):  
Masayuki Takahashi ◽  
Tomoko Yoshino ◽  
Haruko Takeyama ◽  
Tadashi Matsunaga
Keyword(s):  
Whole Blood ◽  
Cell Separation ◽  
Magnetic Particles ◽  
Permanent Magnets ◽  
Bilayer Membrane ◽  
Protein G ◽  
Target Cells ◽  
One Step ◽  
Magnetic Cell Separation ◽  
Bacterial Magnetic Particles

AbstractMagnetic separation of target cells from mixtures, such as peripheral blood and bone marrow, has considerable practical potential in research and medical applications. Among the current cell separation techniques, magnetic cell separation using immunomagnetic particles has been routinely applied and has proven rapidness and simplicity.Magnetospirillum magneticumAMB-1 synthesizes intracellular nano-sized bacterial magnetic particles (BacMPs) that are individually enveloped by a stable lipid bilayer membrane. BacMPs, which exhibit strong ferrimagnetism, can be collected easily with commercially available permanent magnets. In this study, a novel magnetic nanoparticle displaying protein G (protein G-BacMPs) was fabricated, and one-step cell separation for direct cell separation from whole blood was performed using the protein G-BacMPs. B lymphocytes (CD20+cells), which cover less than 0.3×10−2% of whole blood cells, were separated with 93% purity using protein G-BacMPs binding with anti-CD20 monoclonal antibodies. The results of this study demonstrate the utility of protein G-BacMPs and the magnetic cell separation approach based on protein G-BacMPs in numerous applications.

Elastomeric Microfabricated Fluorescence-Activated Cell Sorters

2005 ◽  
Author(s):  
Anne Y. Fu ◽  
Yohei Yokobayashi
Keyword(s):  
Soft Lithography ◽  
Time Course ◽  
Fabrication Process ◽  
Cell Manipulation ◽  
Cross Contamination ◽  
Single Chip ◽  
Cell Sorter ◽  
Materials Used ◽  
On Chip ◽  
Novel Algorithms

This chapter describes the development of elastomeric microfabricated cell sorters that allow for high sensitivity, no cross contamination, and lower cost than any conventional fluorescence-activated cell sorting. The course of this development depends heavily on two key technologies that have advanced rapidly within the past decade: microfluidics and soft lithography. Sorting in the microfabricated cell sorter is accomplished via different means of microfluidic control. This confers several advantages over the conventional sorting of aerosol droplets: novel algorithms of sorting or cell manipulation can be accomplished, dispensing of reagents and biochemical reactions can occur immediately before or after the sorting event, completely enclosed fluidic devices allow for studies of biohazardous/infectious cells or particles in a safer environment, and integration of other technologies can be implemented into the cell sorter. In addition, because of the easy fabrication process and inexpensive materials used in soft lithography, this elastomeric microfabricated cell sorter is affordable to every research laboratory and can be disposable just as a gel in gel electrophoresis, which eliminates any cross contamination from previous runs. Because of the advent of soft lithography, many inexpensive, flexible, and microfabricated devices could be designed to replace flow chambers in conventional flow cytometers. Soft lithography is a micromachining technique that uses the process of rapid prototyping and replica molding to fabricate inexpensive elastomeric microfluidic devices with materials such as plastics and polymers. The elastomeric properties of plastics and polymers allow for an easy fabrication process and for cleaning for reuse or disposal. A variety of biological assays can also be carried out as a result of the chemical compatibilities of different plastic materials with different solvents. More accurate sorting of cells can be accomplished because the sorting region is at or immediately after the interrogation point. On-chip chemical processing of cells has been accomplished and can be observed at any spot on the chip before or after sorting. Time-course measurements of a single cell for kinetic studies can be implemented using novel sorting schemes. Furthermore, linear arrays of channels on a single chip, the multiplex system, may be simultaneously detected by an array of photomultiplier tubes (PMT) for multiple analysis of different channels.

Development of Nano-Microtechnology and Biomedical Applications

2006 ◽  
Author(s):  
Ching-Jen Chen ◽  
Yousef Haik ◽  
Jhunu Chatterjee
Keyword(s):  
Magnetic Field ◽  
Cell Separation ◽  
Magnetic Particles ◽  
Biological Fluid ◽  
Fluid Dynamic ◽  
Human Life ◽  
The Body ◽  
Thermal Engineering ◽  
Biological Cells ◽  
Electro Magnetic Field

Blood, air and water are not only most abundant but also the most important fluids on the earth. Each adult human carries almost a gallon of blood every moment. This paper concerns with the treatment of the blood and discusses in particular the blood cell separation (fluids engineering) and the safe elevation of the body temperature (thermal engineering). Unlike air and water the blood is a biological fluid. Therefore it comes with the complexity of blood composition and disorder of the blood affecting human life and health. This study presents applications of electro-magnetic field on nanomagnetic particles that attach to the blood cells in creating complex fluid dynamic cell separation from the whole blood and creating complex thermal heating, magnetic hyperthermia, for potential use in cancer treatment. In general, biological cells are weak paramagnetic or diamagnetic. Therefore nano-microtechnologies are developed to attach the nanoparticles to the selected cells and to enhance the magnetic susceptibility of the cells to interact with an applied magnetic field. The paper demonstrates that nano to micron size magnetic particles are tagged to the biological cells.

Sign in / Sign up

Export Citation Format

Share Document