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1.
Deterministic lateral displacement (DLD) is a microfluidic size-based particle separation or filter technology with applications in cell separation and enrichment. Currently, there are no cost-effective manufacturing methods for this promising microfluidic technology. In this fabrication paper, however, we develop a simple, yet robust protocol for thermoplastic DLD devices using regulatory-approved materials and biocompatible methods. The final standalone device allowed for volumetric flow rates of 660 μl min−1 while reducing the manufacturing time to <1 h. Optical profilometry and image analysis were employed to assess manufacturing accuracy and precision; the average replicated post height was 0.48% less than the average post height on the master mold and the average replicated array pitch was 1.1% less than the original design with replicated posts heights of 62.1 ± 5.1 μm (mean ± 6 standard deviations) and replicated array pitches of 35.6 ± 0.31 μm.  相似文献   

2.
Zhu J  Xuan X 《Biomicrofluidics》2011,5(2):24111
The separation of particles from a heterogeneous mixture is critical in chemical and biological analyses. Many methods have been developed to separate particles in microfluidic devices. However, the majority of these separations have been limited to be size based and binary. We demonstrate herein a continuous dc electric field driven separation of carboxyl-coated and noncoated 10 μm polystyrene beads by charge in a double-spiral microchannel. This method exploits the inherent electric field gradients formed within the channel turns to manipulate particles by dielectrophoresis and is thus termed curvature-induced dielectrophoresis. The spiral microchannel is also demonstrated to continuously sort noncoated 5 μm beads, noncoated 10 μm beads, and carboxyl-coated 10 μm beads into different collecting wells by charge and size simultaneously. The observed particle separation processes in different situations are all predicted with reasonable agreements by a numerical model. This curvature-induced dielectrophoresis technique eliminates the in-channel microelectrodes and obstacles that are required in traditional electrode- and insulator-based dielectrophoresis devices. It may potentially be used to separate multiple particle targets by intrinsic properties for lab-on-a-chip applications.  相似文献   

3.
We show, via three-dimensional immersed-boundary-finite-element-lattice-Boltzmann simulations, that deformability-based red blood cell (RBC) separation in deterministic lateral displacement (DLD) devices is possible. This is due to the deformability-dependent lateral extension of RBCs and enables us to predict a priori which RBCs will be displaced in a given DLD geometry. Several diseases affect the deformability of human cells. Malaria-infected RBCs, for example, tend to become stiffer than their healthy counterparts. It is therefore desirable to design microfluidic devices which can detect diseases based on the cells'' deformability fingerprint, rather than preparing samples using expensive and time-consuming biochemical preparation steps. Our findings should be helpful in the development of new methods for sorting cells and particles by deformability.  相似文献   

4.
Inertial microfluidics has brought enormous changes in the conventional cell/particle detection process and now become the main trend of sample pretreatment with outstanding throughput, low cost, and simple control method. However, inertial microfluidics in a straight microchannel is not enough to provide high efficiency and satisfying performance for cell/particle separation. A contraction–expansion microchannel is a widely used and multifunctional channel pattern involving inertial microfluidics, secondary flow, and the vortex in the chamber. The strengthened inertial microfluidics can help us to focus particles with a shorter channel length and less processing time. Both the vortex in the chamber and the secondary flow in the main channel can trap the target particles or separate particles based on their sizes more precisely. The contraction–expansion microchannels are also capable of combining with a curved, spiral, or serpentine channel to further improve the separation performance. Some recent studies have focused on the viscoelastic fluid that utilizes both elastic forces and inertial forces to separate different size particles precisely with a relatively low flow rate for the vulnerable cells. This article comprehensively reviews various contraction–expansion microchannels with Newtonian and viscoelastic fluids for particle focusing, separation, and microfluid mixing and provides particle manipulation performance data analysis for the contraction–expansion microchannel design.  相似文献   

5.
We have designed, built, and evaluated a microfluidic device that uses deterministic lateral displacement for size-based separation. The device achieves almost 100% purity and recovery in continuously sorting two, four, and six micrometer microspheres. We have applied this highly efficient device to the purification of fungal (Aspergillus) spores that are spherical (∼4 μm diameter) with a narrow size distribution. Such separation directly from culture using unfiltered A. niger suspensions is difficult due to a high level of debris. The device produces a two to three increase in the ratio of spores to debris as measured by light scatter in a flow cytometer. The procedure is feasible at densities up to 4.4×106 spores∕ml. This is one of the first studies to apply microfluidic techniques to spore separations and has demonstrated that a passive separation system could significantly reduce the amount of debris in a suspension of fungal spores with virtually no loss of spore material.  相似文献   

6.
Isolated mitochondria display a wide range of sizes plausibly resulting from the coexistence of subpopulations, some of which may be associated with disease or aging. Strategies to separate subpopulations are needed to study the importance of these organelles in cellular functions. Here, insulator-based dielectrophoresis (iDEP) was exploited to provide a new dimension of organelle separation. The dielectrophoretic properties of isolated Fischer 344 (F344) rat semimembranosus muscle mitochondria and C57BL/6 mouse hepatic mitochondria in low conductivity buffer (0.025–0.030 S/m) at physiological pH (7.2–7.4) were studied using polydimethylsiloxane (PDMS) microfluidic devices. First, direct current (DC) and alternating current (AC) of 0–50 kHz with potentials of 0–3000 V applied over a channel length of 1 cm were separately employed to generate inhomogeneous electric fields and establish that mitochondria exhibit negative DEP (nDEP). DEP trapping potential thresholds at 0–50 kHz were also determined to be weakly dependent on applied frequency and were generally above 200 V. Second, we demonstrated a separation scheme using DC potentials <100 V to perform the first size-based iDEP sorting of mitochondria. Samples of isolated mitochondria with heterogeneous sizes (150 nm–2 μm diameters) were successfully separated into sub-micron fractions, indicating the ability to isolate mitochondria into populations based on their size.  相似文献   

7.
Microfluidic spirals were used to successfully separate rare solid components from unpretreated human whole blood samples. The measured separation ratio of the spirals is the factor by which the concentration of the rare component is increased due to the Dean effect present in a flow profile in a curved duct. Different rates of dilution of the blood samples with a phosphate-buffered solution were investigated. The diameters of the spherical particles to separate ranged from 2 μm to 18 μm. It was found that diluting the blood to 20% is optimal leading to a separation ratio up to 1.97. Using two spirals continuously placed in a row led to an increase in separation efficacy in samples consisting of phosphate-buffered solution only from 1.86 to 3.79. Numerical investigations were carried out to display the flow profiles of Newtonian water samples and the shear-thinning blood samples in the cross-section of the experimentally handled channels. A macroscopic difference in velocity between the two rheologically different fluids could not be found. The macroscopic Dean flow is equally present and useful to help particles migrate to certain equilibrium positions in blood as well as lower viscous Newtonian fluids. The investigations highlight the potential for using highly concentrated, very heterogeneous, and non-Newtonian fluidic systems in known microsystems for screening applications.  相似文献   

8.
Inertial microfluidics is an emerging class of technologies developed to separate circulating tumor cells (CTCs). However, defining design parameters and flow conditions for optimal operation remains nondeterministic due to incomplete understanding of the mechanics, which has led to challenges in designing efficient systems. Here, we perform a parametric study of the inertial focusing effects observed in low aspect ratio curvilinear microchannels and utilize the results to demonstrate the isolation of CTCs with high purity. First, we systematically vary parameters including the channel height, width, and radius of curvature over a wide range of flow velocities to analyze its effect on size dependent differential focusing and migration behaviors of binary (10 μm and 20 μm) particles. Second, we use these results to identify optimal flow regimes to achieve maximum separation in various channel configurations and establish design guidelines to readily provide information for developing spiral channels tailored to potentially arbitrary flow conditions that yield a desired equilibrium position for optimal size based CTC separation. Finally, we describe a fully integrated, sheath-less cascaded spiral microfluidic device to continuously isolate CTCs. Human breast cancer epithelial cells were successfully extracted from leukocytes, achieving 86.76% recovery, 97.91% depletion rate, and sustaining high viability upon collection to demonstrate the versatility of the device. Importantly, this device was designed without the cumbersome trail-and-error optimization process that has hindered the development of designing such inertial microfluidic systems.  相似文献   

9.
Particle separation is important to many chemical and biomedical applications. Magnetic field-induced particle separation is simple, cheap, and free of fluid heating issues that accompany electric, acoustic, and optical methods. We develop herein a novel microfluidic approach to continuous sheath-free magnetic separation of particles. This approach exploits the negative or positive magnetophoretic deflection to focus and separate particles in the two branches of a U-shaped microchannel, respectively. It is applicable to both magnetic and diamagnetic particle separations, and is demonstrated through the sorting of 5 μm and 15 μm polystyrene particles suspended in a dilute ferrofluid.  相似文献   

10.
Wei Hou H  Gan HY  Bhagat AA  Li LD  Lim CT  Han J 《Biomicrofluidics》2012,6(2):24115-2411513
Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.  相似文献   

11.
Dielectrophoresis (DEP) has been shown to have significant potential for the characterization of cells and could become an efficient tool for rapid identification and assessment of microorganisms. The present work is focused on the trapping, characterization, and separation of two species of Cryptosporidium (C. parvum and C. muris) and Giardia lambia (G. lambia) using a microfluidic experimental setup. Cryptosporidium oocysts, which are 2-4 μm in size and nearly spherical in shape, are used for the preliminary stage of prototype development and testing. G. lambia cysts are 8–12 μm in size. In order to facilitate effective trapping, simulations were performed to study the effects of buffer conductivity and applied voltage on the flow and cell transport inside the DEP chip. Microscopic experiments were performed using the fabricated device and the real part of Clausius—Mossotti factor of the cells was estimated from critical voltages for particle trapping at the electrodes under steady fluid flow. The dielectric properties of the cell compartments (cytoplasm and membrane) were calculated based on a single shell model of the cells. The separation of C. muris and G. lambia is achieved successfully at a frequency of 10 MHz and a voltage of 3 Vpp (peak to peak voltage).  相似文献   

12.
Conventionally, isotachophoresis (ITP) is used for separation of ionic samples according to their electrophoretic mobilities. We demonstrate that the scope of ITP applications may be extended toward particle concentration and separation. Owing to the distributions of electrolyte concentration and electric field inside a transition zone between two electrolytes, a number of different forces act on a small particle. As far as possible, we provide estimates for the order of magnitude of these forces and analyze their scaling with the particle size and the electric-field strength. Furthermore, we experimentally demonstrate that polymer beads of 5 μm diameter dispersed in a high mobility “leading” electrolyte are picked up and carried along by an ITP transition zone which is formed with a low mobility “trailing” electrolyte. By studying the particle positions and trajectories, we show that impurities in the electrolytes play a significant role in the experiments. Additionally, it is experimentally shown that different types of beads can be separated at an ITP transition zone. In particular, beads of 1 μm diameter are not carried along with the transition zone, in contrast to the 5 μm beads. The presented technique thus adds to the portfolio of electrokinetic transport, concentration, and separation methods in microfluidics.  相似文献   

13.
The design of adaptive observers is a common approach for the joint state and parameter-estimation problem. Nonetheless, there are still some obstacles that have to be solved to improve the design of adaptive observers and extend its implementability to a larger class of systems. First, the separation of the state-estimation and the parameter-estimation requires a relative degree one or zero between some known signal and the parameters to be estimated. Second, standard stability proofs for adaptive observers cannot be easily extended to consider the unavoidable presence of sensor noise and unmodeled system uncertainty. Consequently, on the one hand, this work proposed a methodology to relax the relative degree condition through the use of a high-gain observer that will be coupled with the adaptive observer. On the other hand, the stability and performance of the proposed observer scheme will be analyzed by the use of a strict Lyapunov function based on the Mazenc construction, which allows to have provable convergence and to study the effect of sensor noise and model uncertainty through common Lyapunov theory. Finally, the proposed approach is validated in a compartmental epidemiology model.  相似文献   

14.
Many information-retrieval systems provides access to abstracts. For example, Stanford University, through its FOLIO system, provides access to the INSPEC database of abstracts of the literature on physics, computer science, electrical engineering, etc. In this article, this database is studied by using a trace-driven simulation. It focuses on a physical-index design that accommodates truncations, inverted-index caching, and database scaling in a distributed shared-nothing system. All three issues are shown to have a strong effect on response time and throughput. Database scaling is explored in two ways. One way assumes an “optimal” configuration for a single host and then linearly scales the database by duplicating the host architecture as needed. The second way determines the optimal number of hosts given a fixed database size.  相似文献   

15.
Logarithmic finite-size scaling of the O(n) universality class at the upper critical dimensionality (dc = 4) has a fundamental role in statistical and condensed-matter physics and important applications in various experimental systems. Here, we address this long-standing problem in the context of the n-vector model (n = 1, 2, 3) on periodic four-dimensional hypercubic lattices. We establish an explicit scaling form for the free-energy density, which simultaneously consists of a scaling term for the Gaussian fixed point and another term with multiplicative logarithmic corrections. In particular, we conjecture that the critical two-point correlation g(r, L), with L the linear size, exhibits a two-length behavior: follows governed by the Gaussian fixed point at shorter distances and enters a plateau at larger distances whose height decays as with a logarithmic correction exponent. Using extensive Monte Carlo simulations, we provide complementary evidence for the predictions through the finite-size scaling of observables, including the two-point correlation, the magnetic fluctuations at zero and nonzero Fourier modes and the Binder cumulant. Our work sheds light on the formulation of logarithmic finite-size scaling and has practical applications in experimental systems.  相似文献   

16.
Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force field to manipulate particles. In inertial microfluidics, dominant inertial forces cause particles to move across streamlines and occupy equilibrium positions along the faces of walls in flows through straight micro channels. In this study, we systematically analyzed the addition of secondary Dean forces by introducing curvature and show how randomly distributed particles entering a simple u-shaped curved channel are focused to a fixed lateral position exiting the curvature. We found the lateral particle focusing position to be fixed and largely independent of radius of curvature and whether particles entering the curvature are pre-focused (at equilibrium) or randomly distributed. Unlike focusing in straight channels, where focusing typically is limited to channel cross-sections in the range of particle size to create single focusing point, we report here particle focusing in a large cross-section area (channel aspect ratio 1:10). Furthermore, we describe a simple u-shaped curved channel, with single inlet and four outlets, for filtration applications. We demonstrate continuous focusing and filtration of 10 μm particles (with >90% filtration efficiency) from a suspension mixture at throughputs several orders of magnitude higher than flow through straight channels (volume flow rate of 4.25 ml/min). Finally, as an example of high throughput cell processing application, white blood cells were continuously processed with a filtration efficiency of 78% with maintained high viability. We expect the study will aid in the fundamental understanding of flow through curved channels and open the door for the development of a whole set of bio-analytical applications.  相似文献   

17.
We present a simple technique for creating an on-chip magnetic particle conveyor based on exchange-biased permalloy microstripes. The particle transportation relies on an array of stripes with a spacing smaller than their width in conjunction with a periodic sequence of four different externally applied magnetic fields. We demonstrate the controlled transportation of a large population of particles over several millimeters of distance as well as the spatial separation of two populations of magnetic particles with different magnetophoretic mobilities. The technique can be used for the controlled selective manipulation and separation of magnetically labelled species.  相似文献   

18.
Lewpiriyawong N  Yang C 《Biomicrofluidics》2012,6(1):12807-128079
The recent development of microfluidic “lab on a chip” devices requires the need to continuously separate submicron particles. Here, we present a PDMS microfluidic device with sidewall conducting PDMS (AgPDMS) composite electrodes capable of separating submicron particles in hydrodynamic flow. In particular, the device can service dual functions. First, the AgPDMS composite electrodes embedded in a sidewall of the device channel allow for performing AC-dielectrophoretic (DEP) characterization through direct microscopic observation of particle behavior. Characterization experiments are carried out for numerous parameters including particle size, medium conductivity, and AC field frequency to reveal important dielectrophoresis DEP information in terms of the crossover frequency and positive/negative DEP behavior under specific frequencies. Second, the device offers an advantage that sidewall AgPDMS composite electrodes can produce strong DEP effects throughout the entire channel height, and thus the robustness of the on-chip particle separation is demonstrated for continuous separation in a flowing mixture of 0.5 and 5 μm particles with 100% separation efficiency.  相似文献   

19.
Blood cell sorting is critical to sample preparation for both clinical diagnosis and therapeutic research. The spiral inertial microfluidic devices can achieve label-free, continuous separation of cell mixtures with high throughput and efficiency. The devices utilize hydrodynamic forces acting on cells within laminar flow, coupled with rotational Dean drag due to curvilinear microchannel geometry. Here, we report on optimized Archimedean spiral devices to achieve cell separation in less than 8 cm of downstream focusing length. These improved devices are small in size (<1 in.2), exhibit high separation efficiency (∼95%), and high throughput with rates up to 1 × 106 cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for point-of-care blood analysis with high efficiency, low cost, and reduced analysis time.  相似文献   

20.
In this paper we demonstrate a new method for concentrating the set of key-words of a thesaurus. This method is based on a mathematical study that we have carried out into the distribution of characters in a defined natural language.We have built a function f of concentration which generates only a few synonyms. In applying this function to the set of key-words of a thesaurus, we reduce each key-word to four characters without synonymity. (For three characters we have a rate of synonymity of approx. 1/1000th.)A new structure of binary files allows the thesaurus to be contained in a table of less than 700 bytes.  相似文献   

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