Effects of geometry factors on microvortices evolution in confined square microcavities

Recently, microcavities have become a central feature of diverse microfluidic devices for many biological applications. Thus, the flow and transport phenomena in microcavities characterized by microvortices have received increasing research attention. It is important to understand thoroughly the geometry factors on the flow behaviors in microcavities. In an effort to provide a design guideline for optimizing the microcavity configuration and better utilizing microvortices for different applications, we investigated quantitatively the liquid flow characteristics in different square microcavities located on one side of a main straight microchannel by using both microparticle image velocimetry (micro-PIV) and numerical simulation. The influences of the inlet Reynolds numbers (with relatively wider values Re?=?1–400) and the hydraulic diameter of the main microchannel (D_H?=?100, 133 μm) on the evolution of microvortices in different square microcavities (100, 200, 400 and 800 μm) were studied. The evolution and characteristic of the microvortices were investigated in detail. Moreover, the critical Reynolds numbers for the emergence of microvortices and the transformation of flow patterns in different microcavities were determined. The results will provide a useful guideline for the design of microcavity-featured microfluidic devices and their applications.     

Investigation of wax and paper materials for the fabrication of paper-based microfluidic devices

Paper-based microfluidic devices hold great potential in today’s microfluidic applications. They offer low costs, simple and quick fabrication processes, ease of uses, etc. In this work, several wax and paper materials are investigated for the fabrication of paper-based microfluidic devices. A novel method of using wax as a suitable backing to a paper-based analytical device has been demonstrated. Governing equations for the mechanics of the fluid flow in paper-based channels with constant widths have been experimentally validated. Experimental results showing deviations from the governing equations have been verified using fluidic channels with varying widths. There lies the possibility of manipulation of the fluid flow in paper-based microfluidic devices solely using geometric factors. This opens up many potential applications that may require sequential delivery of reagents or samples. Lastly, properties of paper such as the average pore diameter and permeability can be deduced from experimental results.     

Effect of finite reservoir size on electroosmotic flow in microchannels

In electrokinetically driven microfluidic applications, reservoirs are indispensable and have finite sizes. During operation processes, as the liquid level in reservoirs keeps changing as time elapses, a backpressure is generated. Thus, the flow in microfluidic channels actually exhibits a combination of the electroosmotic flow and the time-dependent induced backpressure-driven flow. In this paper, a model is presented to describe the effect of the finite reservoir size on electroosmotic flow in a rectangular microchannel. Important parameters that describe the effect of finite reservoir size on flow characteristics are discussed. A new concept termed as “effective pumping period” is introduced to characterize the reservoir size effect. The proposed model identifies the mechanisms of the finite-reservoir size effects and is verified by experiment using the micro-PIV technique. The results reported in this study can be used for facilitating the design of microfluidic devices.     

Bridging the HASM: An OWL ontology for modeling the information pathways in haptic interfaces software

Haptics technology has received enormous attention to enhance human computer interaction. The last decade has witnessed a rapid progress in haptic application software development due to the fact that the underlying technology has become mature and has opened up novel research areas. In an attempt to organize the path between cause and effect we envision a need for a standard for haptic application software modeling. In order for the software to better enhance the tactile information sensation, flow and perception and also make interaction between humans and haptics more efficient and natural, we need a formal representation of the haptics domain. This article proposes the use of HASM, a haptic applications software modeling ontology to formally model the haptics domain in order to be used during the specifications and design phases of developing software applications for haptic interfaces. The presented ontology captures the existing knowledge in haptics domain, using OWL, and defines the pathways that the haptic information follows between the human and the machine haptic system, using SWRL rules. The haptic ontology that has been developed will be used as a basis to design effective user interfaces and assist the development of software modeling for haptic devices. A case study is demonstrating how this haptic ontology can be used to design a software model that analyzes the perception of a haptic property of an object by interacting with a haptic device.     

Transient flow behavior of complex fluids in microfluidic channels

The ongoing development of microfluidic devices involves the use of highly complex fluids, even of multiphase systems. Despite the great achievements in the development of numerous applications, there is still a lack in the complete understanding of the underlying physics of the observed macroscopic effects. One prominent example is the flow through benchmark contractions where micro- and even macroscopic explanations of some of the occurring flow patterns are still missing. Here, we study the development of the flow profiles of shear thinning semi-dilute polymer solutions in microfluidic planar abrupt contraction geometries. Flow profiles along the narrow channel part are obtained by μ-PIV measurements, whereby the pressure drop along the microfluidic channel as well as the local transient viscosities downstream to the orifice are computed. A relaxation process of the flow profiles from an initially parabolic shape to the flattened steady-state flow profile is observed and traced back to the polymer relaxation.     

Highly integrated polymeric microliquid flow controller for droplet microfluidics

Microfluidic applications demand accurate control and measurement of small fluid flows and volumes, and the majority of approaches found in the literature involve materials and fabrication methods not suitable for a monolithic integration of different microcomponents needed to make a complex Lab-on-a-Chip (LoC) system. The present work leads to a design and manufacturing approach for problem-free monolithic integration of components on thermoplastics, allowing the production of excellent quality devices either as stand-alone components or combined in a complex structures. In particular, a polymeric liquid flow controlling system (LFCS) at microscale is presented, which is composed of a pneumatic microvalve and an on-chip microflow sensor. It enables flow regulation between 30 and 230 μl/min with excellent reproducibility and accuracy (error lower than 5%). The device is made of a single Cyclic Olefin Polymer (COP) piece, where the channels and cavities are hot-embossed, sealed with a single COP membrane by solvent bonding and metalized, after sealing, to render a fully functional microfluidic control system that features on-chip flow sensing. In contrast with commercially available flow control systems, the device can be used for high-quality flow modulation in disposable LoC devices, since the microfluidic chip is low cost and replaceable from the external electronic and pneumatic actuators box. Functionality of the LFCS is tested by connecting it to a microfluidic droplet generator, rendering highly stable flow rates and allowing generation of monodisperse droplets over a wide range of flow rates. The results indicate the successful performance of the LFCS with significant improvements over existing LFCS devices, facing the possibility of using the system for biological applications such as generating distinct perfusion modes in cell culture, novel digital microfluidics. Moreover, the integration capabilities and the reproducible fabrication method enable straightforward transition from prototype to product in a way that is lean, cost-effective and with reduced risk.     

Design and simulation of a thermo transfer type MEMS based micro flow sensor for arterial blood flow measurement

Thermo transfer type MEMS (Micro Electro Mechanical System) based micro flow sensing device have promising potential to solve the limitation of implantable arterial blood flow rate monitoring. The present paper emphasizes on modeling and simulation of MEMS based micro flow sensing device, which will be capable of implantable arterial blood flow rate measurement. It describes the basic design and model architecture of thermal type micro flow sensor. A pair of thin film micro heaters is designed through MEMS micro machining process and simulated using CoventorWare; a finite element based numerical code. A rectangular cross section micro channel has been modeled where in micro heater and thermal sensors are embedded using the same CoventorWare tools. Some promising and interesting results of thermal dissipation depending upon very small amount of flow rate through the micro channel are investigated. It is observed that measuring the variation of temperature difference between downstream and upstream, the variation of fluid flow rate in the micro channel can be measured. The numerical simulation results also shows that the temperature distribution profile of the heated surface depends upon microfluidic flow rate i.e. convective heat transfer is directly proportional to the microfluidic flow rate on the surface of the insulating membrane. The simplified analytical model of the thermo transfer type flow sensor is presented and verified by simulation results, which are very promising for application in arterial blood flow rate measuring in implantable micro devices for continuous monitoring of cardiac output.     

Spiral-shaped inertial stem cell device for high-throughput enrichment of iPSC-derived neural stem cells

Stem cell enrichment plays a critical role in both research and clinical applications. The typical method for stem cell enrichment may use invasive processes and takes a long period of time. Spiral-shaped microfluidic devices, which combine lift and Dean drag forces to direct cells of different sizes into separate trajectories, can be used to noninvasively process samples at a rate of milliliters per minute. This paper presents a simple 2-loop spiral-shaped inertial microfluidic devices with the aid of sheath flow to enrich neural stem cells (NSCs), derived from induced pluripotent stem cells. NSCs and spontaneously differentiated non-neural cells were mixed and flowed through the spiral-shaped devices. Samples collected at the outlets were analyzed for purity and recovery. It was found that the device focused the NSCs into a narrow trajectory, which could then be collected in two out of the eight outlets. The device was tested at different flow rates and found that the most highly enriched fractions (2.1×) with NSCs recovery 93% were achieved at the flow rate (3 ml/min). Next, we extended our investigation from 2-loop design to 10-loop design to eliminate the use of sheath flow. NSCs were enriched to 2.5×, but only 38% of the NSCs were recovered from the most enriched fractions. Spiral-shaped microfluidic devices are capable of rapid, label-free enrichment of target stem cells, and have great potential in point-of-care tissue preparation.     

Micro-injection moulding of polymer microfluidic devices

Microfluidic devices have several applications in different fields, such as chemistry, medicine and biotechnology. Many research activities are currently investigating the manufacturing of integrated microfluidic devices on a mass-production scale with relatively low costs. This is especially important for applications where disposable devices are used for medical analysis. Micromoulding of thermoplastic polymers is a developing process with great potential for producing low-cost microfluidic devices. Among different micromoulding techniques, micro-injection moulding is one of the most promising processes suitable for manufacturing polymeric disposable microfluidic devices. This review paper aims at presenting the main significant developments that have been achieved in different aspects of micro-injection moulding of microfluidic devices. Aspects covered include device design, machine capabilities, mould manufacturing, material selection and process parameters. Problems, challenges and potential areas for research are highlighted.     

Prospects of low temperature co-fired ceramic (LTCC) based microfluidic systems for point-of-care biosensing and environmental sensing

Low temperature co-fired ceramic (LTCC) based microfluidic devices are being developed for point-of-care biomedical and environmental sensing to enable personalized health care. This article reviews the prospects of LTCC technology for microfluidic device development and its advantages and limitations in processing capabilities compared to silicon, glass and polymer processing. The current state of the art in LTCC-based processing techniques for fabrication of microfluidic components such as microchannels, chambers, microelectrodes and valves is presented. LTCC-based biosensing applications are discussed under the classification of (a) microreactors, (b) whole cell-based and (c) protein biosensors. Biocompatibility of LTCC pertaining to the development of biosensors and whole cell sensors is also discussed. Other significant applications of LTCC microfluidic systems for detection of environmental contaminants and toxins are also presented. Technological constraints and advantages of LTCC-based microfluidic system are elucidated in the conclusion. The LTCC-based microfluidic devices provide a viable platform for the development of point-of-care diagnostic systems for biosensing and environmental sensing applications.     

Geometry design of herringbone structures for cancer cell capture in a microfluidic device

Cancer cell detection with high capture efficiency is important for its extensive clinical applications. Herringbone structures in microfluidic devices have been widely adopted to increase the cell capture performance due to its chaotic effect. Given the fact of laminar flow in microfluidic devices, geometry-based optimization acting as a design strategy is effective and can help researchers reduce repetitive trial experiments. In this work, we presented a computational model to track the cell motion and used normalized capture efficiency to evaluate the tumor cell capture performance under various geometry settings. Cell adhesion probability was implemented in the model to consider the nature of ligand–receptor formation and breakage during cell–surface interactions. A facile approach was introduced to determine the two lumped coefficients of cell adhesion probability through two microfluidic experiments. A comprehensive geometric study was then performed by using this model, and results were explained from the fluid dynamics. Although most of the geometric guides agree with the general criterion concluded in the literature, we found herringbone structures with symmetric arms rather than a short arm–long arm ratio of 1/3 are optimal. This difference mainly comes from the fact that our model considers the particulate nature of cells while most studies in the literature optimize the geometry merely relying on mixing effects. Thus, our computational model implemented with cell adhesion probability can serve as a more accurate and reliable approach to optimize microfluidic devices for cancer cell capture.     

Engineered hydrophobicity of discrete microfluidic elements for double emulsion generation

Microfluidic device fabrication has classically utilized methods that have limited devices to specific applications. More recently, discrete microfluidic elements have reimagined the design process of microfluidic device fabrication to that of building blocks that can be constructed in various forms to produce devices of many applications. Here, surface modification of discrete microfluidic elements via initiated chemical vapor deposition is demonstrated. Coated modular elements can quickly assemble to form complex 2-D or 3-D structures with step-like surface energy gradients for applications requiring discrete control of channel surface wettability. This platform is applied toward the generation of double emulsions to show the ease of design and manufacturing over existing methods developed to manage two-phase flows.     

Modular component design for portable microfluidic devices

A new modular design concept for microfluidic devices is proposed and demonstrated in this study. We designed three key modular microfluidic components: pumps, valves, and reservoirs, and demonstrated that a microfluidic device with specific functions can be easily assembled with those key modular components. Our pumps are man-powerable so that the assembled microfluidic devices require no any other power sources like expensive syringe pumps or air compressors. This feature makes the assembled microfluidic devices completely portable. We also combined our assembled device with other existing mixing microchannels to serve as the mixing and loading system in polymerase chain reaction experiment to amplify DNA successfully. This result shows that those modular components can be integrated into other microchannels, implying great potential applications of the modular design.     

Microfluidic systems for diagnostic applications: a review

Because of intensive developments in recent years, the microfluidic system has become a powerful tool for biological analysis. Entire analytic protocols including sample pretreatment, sample/reagent manipulation, separation, reaction, and detection can be integrated into a single chip platform. A lot of demonstrations on the diagnostic applications related to genes, proteins, and cells have been reported because of their advantages associated with miniaturization, automation, sensitivity, and specificity. The aim of this article is to review recent developments in microfluidic systems for diagnostic applications. Based on the categories of various fluid-manipulating mechanisms and biological detection approaches, in-depth discussion of the microfluidic-based diagnostic systems is provided. Moreover, a brief discussion on materials and manufacturing techniques will be included. The current excellent integration of microfluidic systems and diagnostic applications suggests a solid foundation for the development of practical point-of-care devices.     

Instability in Poiseuille flow in a porous medium with slip boundary conditions

We study a model for Poiseuille flow instability in a porous medium of Brinkman type. In particular, we analyse the effect of slip boundary conditions on the onset of instability. Due to numerous applications in micro-electro-mechanical-systems and other microfluidic devices, such a study is essential. We accurately analyse as to when instability will commence and determine the critical Reynolds number as a function of the slip coefficient.     

Deterministic lateral displacement (DLD) in the high Reynolds number regime: high-throughput and dynamic separation characteristics

Recent progress in the development of biosensors has created a demand for high-throughput sample preparation techniques that can be easily integrated into microfluidic or lab-on-a-chip platforms. One mechanism that may satisfy this demand is deterministic lateral displacement (DLD), which uses hydrodynamic forces to separate particles based on size. Numerous medically relevant cellular organisms, such as circulating tumor cells (10–15 µm) and red blood cells (6–8 µm), can be manipulated using microscale DLD devices. In general, these often-viscous samples require some form of dilution or other treatment prior to microfluidic transport, further increasing the need for high-throughput operation to compensate for the increased sample volume. However, high-throughput DLD devices will require a high flow rate, leading to an increase in Reynolds numbers (Re) much higher than those covered by existing studies for microscale (≤?100 µm) DLD devices. This study characterizes the separation performance for microscale DLD devices in the high-Re regime (10?<?Re?<?60) through numerical simulation and experimental validation. As Re increases, streamlines evolve and microvortices emerge in the wake of the pillars, resulting in a particle trajectory shift within the DLD array. This differs from previous DLD works, in that traditional models only account for streamlines that are characteristic of low-Re flow, with no consideration for the transformation of these streamlines with increasing Re. We have established a trend through numerical modeling, which agrees with our experimental findings, to serve as a guideline for microscale DLD performance in the high-Re regime. Finally, this new phenomenon could be exploited to design passive DLD devices with a dynamic separation range, controlled simply by adjusting the device flow rate.     

uFlow: software for rational engineering of secondary flows in inertial microfluidic devices

Approaches to abstract and modularize models of fluid flow in microfluidic devices can enable predictive and rational engineering of microfluidic circuits with rapid designer feedback. The shape of co-flowing streams in the inertial flow regime has become of particular importance for new developments in high throughput microscale manufacturing, biological, and chemical research. In a process known as flow sculpting, the cross-sectional distribution of fluid elements is deformed due to the combined effects of diffusion and transverse advection, which are brought on by interaction with velocity gradients induced by sequences of pillar structures. However, the difficulty in solving the Navier–Stokes equations for complex flow-deforming geometries makes design in this space unintuitive, time-consuming, and costly. To mitigate these issues, we have efficiently embedded flow deformation operations previously relegated to high-performance computing into a free, user-friendly, and cross-platform framework called “uFlow”, to bring flow sculpting to the broader community. uFlow computes flow deformation including both advection and diffusion effects from a single pillar in 25 ms on modern consumer hardware, enabling real-time manual design and exploration of microfluidic devices, and fast visualization of 3D particles fabricated via stop flow lithography or optical transient liquid molding. Advanced numerical routines give instant access to a practically infinite set of flow transformations. We showcase uFlow’s design models, describe their implementation and usage, and validate the algorithms which allow real-time feedback with confocal imaging and cutting-edge microfluidic particle fabrication.     

Single-cell microfluidic impedance cytometry: a review

Lab-on-chip technologies are being developed for multiplexed single cell assays. Impedance offers a simple non-invasive method for counting, identifying and monitoring cellular function. A number of different microfluidic devices for single cell impedance have been developed. These have potential applications ranging from simple cell counting and label-free identification of different cell types or detecting changes in cell morphology after invasion by parasites. Devices have also been developed that trap single cells and continuously record impedance data. This technology has applications in basic research, diagnostics, or non-invasively probing cell function at the single-cell level. This review will describe the underlying principles of impedance analysis of particles. It then describes the state-of-the-art in the field of microfluidic impedance flow cytometry. Finally, future directions and challenges are discussed.     

Thin-film electrode based droplet detection for microfluidic systems

We report on a droplet-producing microfluidic system with electrical impedance-based detection. The microfluidic devices are made of polydimethylsiloxane (PDMS) and glass with thin film electrodes connected to an impedance-monitoring circuit. Immiscible fluids containing the hydrophobic and hydrophilic phases are injected with syringe pumps and spontaneously break into water-in-oil droplet trains. When a droplet passes between a pair of electrodes in a medium having different electrical conductivity, the resulting impedance change signals the presence of the particle for closed-loop feedback during processing. The circuit produces a digital pulse for input into a computer control system. The droplet detector allows estimation of a droplet's arrival time at the microfluidic chip outlet for dispensing applications. Droplet detection is required in applications that count, sort, and direct microfluidic droplets. Because of their low cost and simplicity, microelectrode-based droplet detection techniques should find applications in digital microfluidics and in three-dimensional printing technology for rapid prototyping and biotechnology.     

Scale-up and control of droplet production in coupled microfluidic flow-focusing geometries

A single microfluidic chip consisting of six microfluidic flow-focusing devices operating in parallel was developed to investigate the feasibility of scaling microfluidic droplet generation up to production rates of hundreds of milliliters per hour. The design utilizes a single inlet channel for both the dispersed aqueous phase and the continuous oil phase from which the fluids were distributed to all six flow-focusing devices. The exit tubing for each of the six flow-focusing devices is separate and individually plumbed to each device. Within each flow-focusing device, the droplet size was monodisperse, but some droplet size variations were observed across devices. We show that by modifying the flow resistance in the outlet channel of an individual flow-focusing device it is possible to control both the droplet size and frequency of droplet production. This can be achieved through the use of valves or, as is done in this study, by changing the length of the exit tubing plumbed to the outlet of the each device. Longer exit tubing and larger flow resistance is found to lead to larger droplets and higher production frequencies. The devices can thus be individually tuned to create a monodisperse emulsion or an emulsion with a specific drop size distribution.