Abstract:Cell arrays are of foremost importance for many applications in pharmaceutical research or fundamental biology. Although arraying techniques have been widely investigated for adherent cells, organization of cells in suspension has been rarely considered. The arraying of non-adherent cells using the diamagnetic repulsive force is presented. A planar arrangement of Jurkat cells is achieved at the microscale above high quality microfabricated permanent magnets with remanent magnetization of J(r)≈ 1 T, in the pres… Show more
“…Ta is immiscible with both NdFeB and parylene at the temperatures concerned here [16], [17], ensuring no diffusion from either the NdFeB or Ta capping layer into the MCS culture medium. More information about the fabrication and characterization of the NdFeB micro-magnet arrays can be found in [11], [13], [16]. Arrays of bare Si pillars, used for control experiments, were also coated with a 500 nm layer of parylene.…”
Section: Methodsmentioning
confidence: 99%
“…in the close environment of micron-sized magnetic flux sources [11], [12]. Arrays of micro-magnets, which produce magnetic field gradients up to 10 6 T/m [11], have indeed been used to diamagnetically trap arrays of Jurkat cells, in the presence of a paramagnetic contrast agent [13]. Such micro-magnets can also be used to attract and trap cells functionalized with SPIO nanoparticles [9], [14], [15].…”
Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field’s value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.
“…Ta is immiscible with both NdFeB and parylene at the temperatures concerned here [16], [17], ensuring no diffusion from either the NdFeB or Ta capping layer into the MCS culture medium. More information about the fabrication and characterization of the NdFeB micro-magnet arrays can be found in [11], [13], [16]. Arrays of bare Si pillars, used for control experiments, were also coated with a 500 nm layer of parylene.…”
Section: Methodsmentioning
confidence: 99%
“…in the close environment of micron-sized magnetic flux sources [11], [12]. Arrays of micro-magnets, which produce magnetic field gradients up to 10 6 T/m [11], have indeed been used to diamagnetically trap arrays of Jurkat cells, in the presence of a paramagnetic contrast agent [13]. Such micro-magnets can also be used to attract and trap cells functionalized with SPIO nanoparticles [9], [14], [15].…”
Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field’s value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.
“…The viability was reduced to 54% after 4 h. Similarly, the HaCaT cell viability in the 79 m m solution was 87% after 3-h incubation and 44% after 4-h incubation; however, the cells died immediately when they were exposed to Dulbecco's modified eagle medium (DMEM) containing Gd·DTPA solution. Kauffmann et al [96] studied the viability and growth curve of Jurkat cells in the presence of gadobenate dimeglumine (Gd·BOPTA), gadoterate meglumine (Gd·DOTA) and gadoteridol (Gd·HP·DO3A) contrast agents at different concentrations. Gd·BOPTA was found to be more toxic than the other two solutions.…”
Manipulating particles and cells in magnetic liquids through so-called “negative magnetophoresis” is a new research field. It has resulted in label-free and low-cost manipulation techniques in microfluidic systems and many exciting applications. It is the goal of this review to introduce the fundamental principles of negative magnetophoresis and its recent applications in microfluidic manipulation of particles and cells. We will first discuss the theoretical background of three commonly used specificities of manipulation in magnetic liquids, which include the size, density and magnetic property of particles and cells. We will then review and compare the media used in negative magnetophoresis, which include paramagnetic salt solutions and ferrofluids. Afterwards, we will focus on reviewing existing microfluidic applications of negative magnetophoresis, including separation, focusing, trapping and concentration of particles and cells, determination of cell density, measurement of particles' magnetic susceptibility, and others. We will also examine the need for developing biocompatible magnetic liquids for live cell manipulation and analysis, and its recent progress. Finally, we will conclude this review with a brief outlook for this exciting research field.
“…Microfluidic manipulation of cells in magnetic liquids, 1 i.e., negative magnetophoresis, led to a number of recent applications in cell separation, 1–4 trapping and focusing, 5–8 and density measurements. 9–13 Its working principle is as follows: cells without any labels placed inside a uniformly magnetic media – magnetic liquids, act as “magnetic holes”.…”
This paper reports a biocompatible and label-free cell separation method using ferrofluids that can separate a variety of low-concentration cancer cells from cell culture lines (~100 cancer cells/mL) from undiluted white blood cells, with a throughput of 1.2 mL/h and an average separation efficiency of 82.2%. The separation is based on size difference from cancer cells and white blood cells, and is conducted in a custom-made biocompatible ferrofluid that retains not only excellent short-term viabilities, but also normal proliferations of 7 commonly used cancer cell lines. A microfluidic device is designed and optimized specifically to shorten the exposure time of live cells in ferrofluids from hours to seconds, by eliminating time-consuming off-chip sample preparation and extraction steps and integrating them on-chip to achieve one-step process. As a proof-of-concept demonstration, a ferrofluid with 0.26% volume fraction was used in this microfluidic device to separate spiked cancer cells from cell lines at a concentration of ~100 cells/mL from white blood cells with a 1.2 mL/h throughput. The separation efficiencies were 80±3%, 81±5%, 82±5%, 82±4%, and 86±6% for A549 lung cancer, H1299 lung cancer, MCF-7 breast cancer, MDA-MB-231 breast cancer, and PC-3 prostate cancer cell lines, respectively. Separated cancer cells purity was between 25.3% and 28.8%. In addition, separated cancer cells from this strategy showed an average short-term viability of 94.4±1.3% and separated cells were cultured and demonstrated normal proliferation to the confluence even after the separation process. Owning to its excellent biocompatibility and label-free operation, and its ability to recover low concentration of cancer cells from white blood cells, this method could lead to a promising tool for rare cell separation.
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