Silicon membrane filter designed by fluid dynamics simulation and near-field stress analysis for selective cell enrichment.
TL;DR: A filtering system that can quickly separate and highly concentrate cells from a large volume of solution, depending on their size, using a silicon membrane filter with various pore designs is developed.
Abstract: Selective cell enrichment technologies can play an important role in both diagnostic and therapeutic areas. However, currently used cell sorting techniques have difficulties in rapidly isolating only the desired target cells from a large volume of body fluids. In this work, we developed a filtering system that can quickly separate and highly concentrate cells from a large volume of solution, depending on their size, using a silicon membrane filter. To overcome the problems caused by material limitations of the brittle silicon, we designed a novel membrane filter with various pore designs. From these designs, the most optimal design with high pore density, while preventing crack formation was derived by applying fluid dynamics simulation and near-field stress analysis. The membrane filter system using the selected design was fabricated, and cell filtration performance was evaluated. The LNCaP cell in horse blood was recovered up to 86% and enriched to 187-fold compared to initial cell populations after filtration at a flow rate of 5 mL/min. The results demonstrate that the filter presented in this study can rapidly and selectively isolate target cells from a large volume of body fluid sample.
References
More filters
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TL;DR: This review examines the breadth of microfluidic cell sorting technologies, while focusing on those that offer the greatest potential for translation into clinical and industrial practice and that offer multiple, useful functions.
Abstract: Accurate and high throughput cell sorting is a critical enabling technology in molecular and cellular biology, biotechnology, and medicine While conventional methods can provide high efficiency sorting in short timescales, advances in microfluidics have enabled the realization of miniaturized devices offering similar capabilities that exploit a variety of physical principles We classify these technologies as either active or passive Active systems generally use external fields (eg, acoustic, electric, magnetic, and optical) to impose forces to displace cells for sorting, whereas passive systems use inertial forces, filters, and adhesion mechanisms to purify cell populations Cell sorting on microchips provides numerous advantages over conventional methods by reducing the size of necessary equipment, eliminating potentially biohazardous aerosols, and simplifying the complex protocols commonly associated with cell sorting Additionally, microchip devices are well suited for parallelization, enabling complete lab-on-a-chip devices for cellular isolation, analysis, and experimental processing In this review, we examine the breadth of microfluidic cell sorting technologies, while focusing on those that offer the greatest potential for translation into clinical and industrial practice and that offer multiple, useful functions We organize these sorting technologies by the type of cell preparation required (ie, fluorescent label-based sorting, bead-based sorting, and label-free sorting) as well as by the physical principles underlying each sorting mechanism
845 citations
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TL;DR: Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for on-chip genomic analysis.
Abstract: This paper reports on the comparison analysis of four main types of silicon-based microfilter for isolation of white blood cells (WBCs) from red blood cells (RBCs) in a given whole blood. The microfilter designs, namely, weir, pillar, crossflow, and membrane, all impose the same cut-off size of 3.5 mum to selectively trap WBCs. Using human whole blood, the microfilters have been characterized and compared for their blood handling capacity, WBCs trapping efficiency and RBCs passing efficiency. Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for on-chip genomic analysis.
267 citations
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TL;DR: It will be shown that depending on the treatment method, the diffusion of the lipids can be adjusted approximately threefold without altering the composition, meaning that as the bilayer-support interaction decreases, it becomes easier to form coexisting liquid-ordered and liquid-disordered domains.
193 citations
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TL;DR: A review of microfluidic approaches realized to successfully fractionate one or more blood components is presented in this article, where techniques to separate plasma from hematologic cellular components as well as isolating blood cells of interest including certain rare cells are discussed.
Abstract: Blood, a complex biological fluid, comprises 45% cellular components suspended in protein rich plasma. These different hematologic components perform distinct functions in vivo and thus the ability to efficiently fractionate blood into its individual components has innumerable applications in both clinical diagnosis and biological research. Yet, processing blood is not trivial. In the past decade, a flurry of new microfluidic based technologies has emerged to address this compelling problem. Microfluidics is an attractive solution for this application leveraging its numerous advantages to process clinical blood samples. This paper reviews the various microfluidic approaches realized to successfully fractionate one or more blood components. Techniques to separate plasma from hematologic cellular components as well as isolating blood cells of interest including certain rare cells are discussed. Comparisons based on common separation metrics including efficiency (sensitivity), purity (selectivity), and throughput will be presented. Finally, we will provide insights into the challenges associated with blood-based separation systems towards realizing true point-of-care (POC) devices and provide future perspectives.
163 citations
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01 Nov 1988-Materials Science and Engineering A-structural Materials Properties Microstructure and Processing
TL;DR: In this article, the authors have demonstrated that the solid particle erosion rate can be taken as a simple and highly reproducible statistical measure of the susceptibility of silicon and GaAs to contact damage in the micron range.
Abstract: In recent years, the growing field of semiconductor micromechanics has created an increasing demand for strength data on semiconductors and for adequate tests and evaluations of their mechanical properties. In a recently published paper, the present authors have demonstrated that the solid particle erosion rate can be taken as a simple and highly reproducible statistical measure of the susceptibility of silicon and GaAs to contact damage in the micron range. In the present work the scope is broadened to include several new crystal orientations (and one new doping level), as well as three other materials: germanium, InP and InAs, for which the hardness and fracture toughness K Ic values are determined by means of the indentation technique. K Ic values are also derived from erosion data by means of a recently reported brittle fracture model, based on non-lateral spalling in single-crystal semiconductors. These values are compared with results obtained by the indentation technique and conventional test methods reported in the literature. Fracture surface energies are deduced from the experimental K Ic results. The materials tested are ranked with respect to elastic properties, microhardnesses, fracture toughnesses, and sensitivities to contact damages in general. The influence of crystallographic orientation on room temperature microfracture properties is clearly established, but the corresponding influence on microhardness is found to be rather limited. The influence of doping on the room temperature mechanical properties is noticeable but small.
108 citations