A portable,hand-powered microfluidic device for sorting of biological particles

Manually hand-powered portable microfluidic devices are cheap alternatives for point-of-care diagnostics. Currently, on-field tests are limited by the use of bulky syringe pumps, pressure controller and equipment. In this work, we present a manually operated microfluidic device incorporated with a groove-based channel. We show that the device is capable to effectively sort particles/cells by manual hand powering. First, the grooved-based channel with differently sized polystyrene particles was characterized using syringe pumps to study their distributions under various flow rate conditions. Afterward, the particle mixtures were sorted manually using hand power to verify the capability of this device. Finally, the manually operated device was used to sort platelets from peripheral blood mononuclear cells (PBMCs). The platelets were collected with a purity of ~ 100%. The purity of PBMCs was enhanced from 0.8 to 10.4% after multiple processes which results in an enrichment ratio of 13.8. During the process of manual hand pumping, the flow fluctuation caused by unstable injection will not influence the sorting performance. Due to its simplicity, this manually operated microfluidic chip is suitable for outfield settings.     

Design,simulation and experiment of electroosmotic microfluidic chip for cell sorting

A microfluidic cell sorting chip has been developed using micromachining technology, where electroosmotic flow (EOF) is exploited to drive and switch cells. For this electroosmotically driven system, it is found that the effect of induced hydrostatic pressure caused by unequal levels in solution reservoirs is not negligible. In this work, the numerical simulation of EOF and opposing pressure induced flow in microchannels is presented and the velocity profiles in the microchannels are measured experimentally using microparticle imaging velocimetry (PIV) system. The result shows that the final resulting velocity is the superposition of the two flows. A total volume of 0.305 μl is transported in the 50 μm microchannel and the back flow occurs after 240 s transportation. The task of sorting cells is realized at the switching structure by adjusting the electric fields in the microchannels. The performance of the cell sorting chip is optimized by investigating the effect of different switching structures. A Y-junction switching structure with 90° switching angle is highly recommended with simulated leakage distance of 53 μm and switching time of 8 ms.     

A facile on-demand droplet microfluidic system for lab-on-a-chip applications

We present a facile microfluidic droplet-on-demand (DOD) system in which a pulsed pressure generated by a high-speed solenoid valve is used to control the formation and movement of water-in-oil emulsion droplets in a T-junction microchannel. We investigated the working principle of the DOD system and established a scaling model for the droplet volume in terms of the amplitude and duration of the pulse and the hydraulic resistance of the injection channel. The droplet formation was characterized in three designs at various pressure pulses. The experimental results support our scaling model very well. In the DOD system we developed, nanoliter-volume droplets with a throughput of a few droplets per second were on-demand generated. Moreover, we examined the applicable scope of the DOD system. As examples of practical applications of the DOD system, we demonstrated a digital display module to show droplets formed at a prescribed time and a droplet array with a concentration gradient to show droplets formed with a precise volume. We expect our work can provide design guidelines for a robust DOD system and improve the capabilities of droplet-based microfluidics in ‘lab-on-a-chip’ systems.     

A microfluidic chip for heterogeneous immunoassay using electrokinetical control

This article presents the development of a novel, automated, electrokinetically controlled heterogeneous immunoassay on a poly(dimethylsiloxane) (PDMS) microfluidic chip. A numerical method has been developed to simulate the electrokinetically driven, time-dependent delivery processes of reagents and washing solutions within the complex microchannel network. Based on the parameters determined from the numerical simulations, fully automated on-chip experiments to detect Helicobacter pylori were accomplished by sequentially changing the applied electric fields. Shortened assay time and much less reagent consumptions are achieved by using this microchannel chip while the detection limit is comparable to the conventional assay. There is a good agreement between the experimental result and numerical prediction, demonstrating the effectiveness of using CFD to assist the experimental studies of microfluidic immunoassay.     

A power-free deposited microbead plug-based microfluidic chip for whole-blood immunoassay

We present a deposited microbead plug (DMBP)-based microfluidic chip capable of performing plasma extraction and on-chip immunoassay. The DMBP used as a porous blood filter provides pure blood plasma without the contamination of blood cells or beads. Capillary-driven flow eliminates the requirement of external pumps. The human IgG and goat anti-human IgG sample-to-answer assay was performed in this chip within 600 s using only a 10 μl whole-blood sample. This easy-to-use, rapid, inexpensive, and disposable DMBP-based chip holds a great promise for point-of-care application.     

A microfluidic pore model to study the migration of fine particles in single-phase and multi-phase flows in porous media

Microsystem Technologies - Fine particles within porous media may migrate with the flowing fluid and cause bridging or clogging in the pore space. Bridging and clogging reduce the flow permeability...     

A robust hybrid stabilization strategy for equilibria

For an equilibrium of a general dynamical system, the domain of stability of a linear feedback controller is enlarged by the use of a general “hybrid” or “switching” strategy. The strategy is illustrated for numerical simulations of an inverted double pendulum on a cart     

A robust strategy for real-time process monitoring

An operator support system (OSS) is proposed to reliably retain salient information in a high dimensional and correlated database, to uncover linear and nonlinear correlations among variables, to reconstruct failed/unavailable sensors, and to assess process-operating performance in the presence of noise and outliers. The proposed strategy carries out the task in three steps. In the first step, a robust tandem filter is used to suppress noise and reject any outlying observations. Next, an orthogonal nonlinear principal component analysis network is utilized to optimally retain a parsimonious representation of the system. In the final step, the process status is checked against the normal operating region defined by kernel density estimation, and failed/unavailable sensors are reconstructed via constrained optimization and the trained network. The strategy is demonstrated in real-time using a pilot-scale distillation column.     

A microfluidic chip of multiple-channel array with various oxygen tensions for drug screening

Oxygen participates in numbers of cellular activities and behaviors in both normal and pathological tissues. In physiological microenvironment, oxygen tension is generally below 21 % and varies in different species, states and regions of organs. However, present studies of cellular behavior in vitro are performed in an ambient level, which is not conformity to the reality in vivo. In this study, a microfluidic device was developed to generate controllable oxygen tensions on a multiple-channel array chip for high-throughput drug screening. Controlling various concentrations of chemical reagents with confined flow rate, specific oxygen tensions can be established from 1.6 to 21 %, where the oxygen tension of each channel can be modulated in demand. When the concentrations of pyrogallol change from 100 to 700 μg/mL with the flow rate of 5 μL/min, oxygen tensions in cell chambers range from 12.5 to 3.87 %. Pyrogallol with the concentration of 0 μg/mL is used as the control group to obtain 20.9 % oxygen condition. The developed microfluidic chip was used to investigate the cytotoxicity of TPZ and cisplatin, and the results demonstrate different manners of two oxygen-sensitive anti-tumor drugs in oxygen-dependent cytotoxic responses. Due to its character, the microfluidic device is believed to establish any desired and measurable oxygen tension distribution for pharmacology development, which is promising to improve efficiency and reduce tedious operation for pharmaceutical studies.     

A simultaneous sample-and-filter strategy for robust multi-structure model fitting

In many robust model fitting methods, obtaining promising hypotheses is critical to the fitting process. However the sampling process unavoidably generates many irrelevant hypotheses, which can be an obstacle for accurate model fitting. In particular, the mode seeking based fitting methods are very sensitive to the proportion of good/bad hypotheses for fitting multi-structure data. To improve hypothesis generation for the mode seeking based fitting methods, we propose a novel sample-and-filter strategy to (1) identify and filter out bad hypotheses on-the-fly, and (2) use the remaining good hypotheses to guide the sampling to further expand the set of good hypotheses. The outcome is a small set of hypotheses with a high concentration of good hypotheses. Compared to other sampling methods, our method yields a significantly large proportion of good hypotheses, which greatly improves the accuracy of the mode seeking-based fitting methods.     

一种新的间歇过程鲁棒在线监控方法

多向主元分析(MPCA)的统计监控模型,因为易受建模数据中离群点的影响,还需预估新批次未反应完的数据,所以提出一种新的间歇过程鲁棒在线监控法。先利用改进尺度的CDC/MVT算法获取常规建模的批次数据;再用多模型非线性结构代替传统的MPCA单模型线性化结构,并提出确定时滞变量的算法。前者用于监控β-甘露聚糖酶发酵批过程,并与移动窗多向主元分析(MWMPCA)法相比,即使建模数据中存在离群点,前者仍能获得正确的监控结果,减少建模时对数据的要求;同时克服了MPCA不能处理实时性的问题,避免了MPCA在线应用时预测值的误差;更能精确描述过程的故障,准确性和实时性良好。     

A robust adaptive strategy for the nonlinear Poisson equation

Our goal is to develop adaptive strategies in order to obtain finite element solutions of the partial differential equation-Δu=f(u) in a bounded domain Ω ? ?². In practice one works with an approximationf _h off. But this may give wrong results if we do not control the coresponding approximation error on coarse girds. In this work we develop a strategy that is robust, but less efficient, in the beginning of the adaptive algorithm and switches to a more efficient procedure if certainsaturation conditions are satisfied. The results are based on a posteriori saturation criterial that measure the quality of the approximation solution.     

A novel three-dimensional microfluidic platform for on chip multicellular tumor spheroid formation and culture

The formation of three-dimensional (3D) multicellular cell spheroids such as microspheres and embryoid bodies has recently gained much attention as a useful cell culture technique, but few studies have investigated the suitability of glass for spheroids formation and culture. In this work, we present a novel three-dimensional microfluidic device made of poly(dimethylsiloxane) (PDMS) and glass for the easy and rapid synthesis and culture of tumor spheroid. The cell culture unit is composed of an array of microwells on the bottom of a glass plate, bigger microwells and elastomeric microchannels on the top of a PDMS plate. Cell suspension can be easily introduced into the cell culture unit and exchange with the external liquid environment by the microfluidic channels. A single tumor spheroid can be formed and cultured in each glass cell culture chamber, the surface of which was modified with poly(vinyl alcohol) to render it to be resistant to cell adhesion. As the cell culture medium could be replaced, spheroids of the human breast cancer (MCF-7) cells were cultured on the chip for 3 days, reaching the diameters of about 150 μm. Furthermore, the MCF-7 cells were successfully cultured on the chip in 2D and 3D culture modes. Results have shown that glass is well suitable for multicellular tumor spheroids culture. The established platform provides a convenient and rapid method for tumor spheroid culture, which is also adaptable for anticancer drug screening and fundamental biomedical research in cell biology.     

A silicone-based microfluidic chip grafted with carboxyl functionalized hyperbranched polyglycerols for selective protein capture

A poly(dimethylsiloxane) (PDMS)-based functional microfluidic device containing a charged matrix of PDMS pillar arrays grafted with hyperbranched polyglycerols (HPGs) was developed. Samples of PDMS were modified with allylamine plasma to form amine groups on the surface prior to the covalent grafting of succinimdyl ester-functionalized HPGs. The anionic functionality of the PDMS channel matrices was developed by altering the number of carboxyl groups present on the HPGs. The grafting of HPGs onto PDMS plates was investigated via contact angle measurement and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), while the grafting of the inside channel was investigated by electroosmotic flow (EOF) measurements. The charge density on grafted HPG was optimized to minimize the nonspecific protein adsorption and increase the selective capture of positively charged proteins. A proof-of-concept device was fabricated on PDMS and demonstrated that the device selectively captures positively charged protein (avidin) from a mixture of bovine serum albumin (BSA)-avidin at pH 7.4 in phosphate buffered saline (PBS). In order to increase the capture efficiency of the proteins in this PDMS-based device, pillar arrays have been fabricated within the channel. As a demonstration, the new device separated two proteins with an avidin capture efficiency of 100 ± 2.95% per 3 min from a 0.02 mg/ml protein solution (avidin:BSA wt ratio: 1:1). This new microfluidic-based device shows a great deal of promise as a tool for protein capture and analysis.     

A modified microfluidic chip for fabrication of paclitaxel-loaded poly(l-lactic acid) microspheres

In this article, we present a simple PDMS surface modification method based on poly(vinyl alcohol)/glycerol (PVA/Gly) solution immersion, self-assembled absorption, and heat treatment. The results of contact angle and ATR-FTIR demonstrate the superhydrophilic surface in modified PDMS. It can allow for the stable production of monodisperse droplet in a highly reproducible manner. In addition, we demonstrate the fabrication of monodisperse paclitaxel (PTX) loaded poly(l-lactic acid) (PLLA) microspheres on this kind of modification chip with solvent evaporation. The PLLA microspheres can be adjusted to a range of different sizes depending on the system flow rate. Determination of microsphere size is carried out by optical microscopy and image analysis to reveal less than 4% variation in microsphere size. Compared with the results of published papers, the presented data demonstrate that PTX-loaded PLLA microspheres show good physical properties (spherical and discrete), high-drug loading, encapsulation efficiency, a small initial burst, and sustained-release behavior due to outstanding monodispersity. With the characteristic to prepare high-quality, monodisperse, biodegradable microspheres, the versatile and simple microfluidic method facilitates the development of more reliable and reproducible drug delivery systems, which have great potential to benefit pharmaceutical and biological applications.     

A method of water pretreatment to improve the thermal bonding rate of PMMA microfluidic chip

A new method of water pretreatment for thermal bonding polymethylmethacrylate microfluidic chip was proposed in this paper. The bonding rate (effective bonding area) of microfluidic chip under different pretreatment time was studied and the mechanism of this method was discussed. The main thermal bonding parameters were as follows: bonding pressure 1.4 ~ 1.9 Mpa, temperature 91 ~ 93°C, time 360 s. The experimental result shows that this method can increase the effective bonding area, improve the bonding quality of the microfluidic chip compared to the conventional thermal bonding method. The optimal water pretreatment time is 1 h with the bonding rate increased by 34% compared with the conventional thermal bonding method. The pollution to the micro-channels is avoided and the performance of the microfluidic system will be reserved with this water pretreatment method. This method is available for the biochemical analysis of the chip, and holds the benefits of easy-operation, high-efficiency and low-cost properties.     

A robust projection plane selection strategy for UAV image stitching

Unmanned Aerial Vehicles (UAVs) are the most popular way to collect ground data today, thanks to their low cost and matchless convenience. However, UAVs are prone to unstable flight poses because they are so light in weight, which has resulted in a new challenge for UAV image stitching. In this paper, we propose a robust approach to stitch UAV images captured from approximately planar scenes without pose parameters assistance. The key idea of the proposed framework lies in an effective projection plane selection strategy, which is capable of resisting the perspective distortion from existing pose-perturbed images. To select a reasonable reference image as the projection plane, we first divide all the images into two groups (stable group and unstable group) according to their registration error under the affine model. Then, a specifically designed approach is used to define a weighted topological graph, which guarantees that the reference image is selected from the stable group while maintaining a global minimum accumulated registration error. Based on our cost topological graph, each unstable group image is locally attached to a stable group image via a homography. Finally, alignment parameters of all the stable group images are solved using affine model, after which global optimization is performed on the model of both groups. Comparing our results to those of the conventional approaches indicates that our proposed approach produced superior results in several challenging experiments involving both qualitative and quantitative evaluation.     

A robust dynamic planning strategy for lot-sizing problems with stochastic demands

We consider the question of generating robust plans for production planning problems under uncertainty. In particular, we present an alternative approach to generate robust solutions for lot-sizing problems with stochastic demand. The proposed approach is dynamic and includes a decision rule that guides the planner. The decision rule parameters are determined so that the number of expected planning adaptations and their magnitudes are under control. The robust approach and its related models are presented together with some computational results to show how it performs compared to other approaches.     

A dual Newton strategy for scenario decomposition in robust multistage MPC

This paper considers the solution of tree‐structured quadratic programs as they may arise in multistage model predictive control. In this context, sampling the uncertainty on prescribed decision points gives rise to different scenarios that are linked to each other via the so‐called nonanticipativity constraints. Previous work suggests to dualize these constraints and apply Newton's method on the dual problem to achieve a parallelizable scheme. However, it has been observed that the globalization strategy in such an approach can be expensive. To alleviate this problem, we propose to dualize both the nonanticipativity constraints and the dynamics to obtain a computationally cheap globalization. The dual Newton system is then reformulated into small highly structured linear systems that can be solved in parallel to a large extent. The algorithm is complemented by an open‐source software implementation that targets embedded optimal control applications.     

A microfluidic device for rapid concentration of particles in continuous flow by DC dielectrophoresis

This article presents a microfluidic device (so called concentrator) for rapid and efficient concentration of micro/nanoparticles using direct current dielectrophoresis (DC DEP) in continuous fluid flow. The concentrator is composed of a series of microchannels constructed with PDMS-insulating microstructures to focus efficiently the electric field in the flow direction to provide high field strength and gradient. Multiple trapping regions are formed within the concentrator. The location of particle trapping depends on the strength of the electric field applied. Under the experimental conditions, both streaming movement and DEP trapping of particles simultaneously take place within the concentrator at different regions. The former occurs upstream and is responsible for continuous transport of the particles, whereas the latter occurs downstream and rapidly traps the particles delivered from upstream. The observation agrees with the distribution of the simulated electric field and DEP force. The performance of the device is demonstrated by successfully and effectively concentrating fluorescent nanoparticles. At the sufficiently high electric field, the device demonstrates a trapping efficiency of 100%, which means downstream DEP traps and concentrates all (100%) the incoming particles from upstream. The trapping efficiency of the device is further studied by measuring the fluorescence intensity of concentrated particles in the channel. Typically, the fluorescence intensity becomes saturated in Trap 1 by applying the voltage (400 V) for >2 min, demonstrating that rapid concentration of the nanoparticles (10⁷ particles/ml) is achieved in the device. The microfluidic concentrator described can be implemented in applications where rapid concentration of targets is needed such as concentrating cells for sample preparation and concentrating molecular biomarkers for detection.