DESIGN AND MIXING PERFORMANCE OF PASSIVE MICROMIXERS: A CRITICAL REVIEW

This study extracts and reports notable findings on passive micromixers by conducting an exhaustive review of designs, their features, and mixing performance. The study has covered the relevant articles on passive micromixers published from 2010 to 2020. The analysis of filtered and selected articles sums up passive micromixers into four categories: designed inlets, designed mixing-channel, lamination-based, and flow obstacles-based. The prominent mixing channel categories identified in the study are split-and-recombine (SAR), convergent-divergent (C-D), and mixed (SAR, C-D, and others). Moreover, differences in mixing channel designs, number of inlets, and evaluation methods have been used in comparing the mixing performance of passive micromixers. The SAR and the obstacles-based micromixers were found to outperform the others. The designs covered in the present review show significant improvements in the mixing index. However, these studies were conducted in an isolated environment, and most of the time, their fabrication and device integration issues were ignored. The assortment and critical analysis of micromixers based on their design features and flow parameters will be helpful to researchers interested in designing new passive micromixers for microfluidic applications

Evaluating the mixing performance in a planar passive micromixer with t-shape and SAR mixing chambers: comparative study

In Microfluidic devices have gained significant interest in various fields, including biomedical diagnostics, environmental preservation, animal epidemic avoidance, and food safety regulation. Micromixing phenomena are crucial for these devices' functionality, as they accurately and efficiently manipulate fluids within microchannels. The process aims to blend samples accurately and swiftly within these scaled-down devices, governed by the promotion of dispersion among distinct fluid species or particles. Advancements in passive and active micromixers have led to innovative designs incorporating diverse processes to enhance mixing efficiency. Examples include two-dimensional impediments, controlled imbalanced collisions, and complex configurations like spiral and convergence-divergence structures. Active micromixers use external cues to initiate and regulate mixing processes, including thermal, magnetic, sound, pressure, and electrical fields. The trajectory of micromixing technologies is significantly influenced by current developments in microfluidics. One notable advancement is the incorporation of micromixers into 3D printing methodologies, facilitating the development of adaptable microfluidic systems. Additionally, the incorporation of microfluidic principles into paper-based channels creates opportunities for the development of cost-effective and portable diagnostic devices. The process of micro-mixing is critical in boosting the functionalities of these devices.</p

Passive Micromixers

Micro-total analysis systems and lab-on-a-chip platforms are widely used for sample preparation and analysis, drug delivery, and biological and chemical syntheses. A micromixer is an important component in these applications. Rapid and efficient mixing is a challenging task in the design and development of micromixers. The flow in micromixers is laminar, and, thus, the mixing is primarily dominated by diffusion. Recently, diverse techniques have been developed to promote mixing by enlarging the interfacial area between the fluids or by increasing the residential time of fluids in the micromixer. Based on their mixing mechanism, micromixers are classified into two types: active and passive. Passive micromixers are easy to fabricate and generally use geometry modification to cause chaotic advection or lamination to promote the mixing of the fluid samples, unlike active micromixers, which use moving parts or some external agitation/energy for the mixing. Many researchers have studied various geometries to design efficient passive micromixers. Recently, numerical optimization techniques based on computational fluid dynamic analysis have been proven to be efficient tools in the design of micromixers. The current Special Issue covers new mechanisms, design, numerical and/or experimental mixing analysis, and design optimization of various passive micromixers

Analysis, Design and Fabrication of Micromixers

This book includes an editorial and 12 research papers on micromixers collected from the Special Issue published in Micromachines. The topics of the papers are focused on the design of micromixers, their fabrication, and their analysis. Some of them proposed novel micromixer designs. Most of them deal with passive micromixers, but two papers report studies on electrokinetic micromixers. Fully three-dimensional (3D) micromixers were investigated in some cases. One of the papers applied optimization techniques to the design of a 3D micromixer. A review paper is also included and reports a review of recently developed passive micromixers and a comparative analysis of 10 typical micromixers

Design and microfabrication of new automatic human blood sample collection and preparation devices

For self-sampling or collection of blood by health personal related to point-ofcare diagnostics in health rooms, it may often be necessary to perform automatic collection of blood samples. The most important operation that needs to be done when handling whole blood is to be able to combine automatic sample collection with optimal mixing of anticoagulation liquid and weak xatives. In particular before doing any transport of a sample or point-of-care nucleic acid diagnostics (POCNAD) it is very important to x the gene expression at the time of collection. It is also important to concentrate and separate out the white blood cells of interest from the whole blood before further detection. An automatic sample collection module with a microneedle array in combination with a micromixer is proposed for the blood collection in typical nurse or health rooms. An automatic human blood preparation module is also suggested that could be used for pre-mixing, concentration and lyses. Despite that the concept of microneedle has been intensively studied since several decades ago, the fabrication still remains very challenging. Major challenges concern the high aspect ratio of microneedle structure. In addition, the microneedles have to be su ciently strong to avoid fracture and cracks during practical implementation. The other challenge with small microchannel dimensions on a chip is the lack of turbulences (including fluids that operate with Reynolds number smaller than 2000). Hence a long mixing length is required for good mixing quality. This doctoral thesis focus on the following challenges: (i) design and optimize a continuous concentration and separation unit, (ii) optimize and improve the fabrication process of high aspect ratio metallic microneedle, (iii) develop and investigate the mixing performance of a passive planar micromixer with ellipse-like micropillars, (iv) integrate and demonstrate the pretreatment system. Article I reported the design and optimization of non-clogging counter-flow microconcentrator for enriching epidermoid cervical carcinoma cells. The counter-flow concentration unit with turbine blade-like micropillars were proposed in microconcentrator design. Due to the organization of these micropillar units the functionality cause a unique system of continuous concentration and separation. Due to the unusual geometrical-pro les and extraordinary micro fluidic performance, the cells blocking does not occur even at permeate entrances. The excellent concentration ratio of a fi nal microconcentrator was presented in both numerical and experimental results. Article II proposed a simple and low cost micromixer for laminar blood mixing. The design of micromixer unit was modifi ed from the counter-flow concentration units which mentioned in Article I. The e ciency of the splitting and recombination (SAR) micromixer was examined by theoretical methods, including finite element method and verifi ed by measurement results. Numerical results show that micromixer with ellipse-like micropillars have a well mixing status when its mixing effi ciency is higher than 80% as Re 6 1. Article III presented that the e ciency of the SAR micromixer for cell lysis. Some bacteria, especially gram-positive, may be diffi cult to lyse with conventional lysis bu er. If the cells are not properly lysed, the quality of the analysis results might suff er. With a splitting and recombination concept, homogeneous mixing can be obtained in short distance. Hence, the quality of the sample after lysis for further process (Nucleic Acid Purifi cation, Nucleic Acid Sequence Based Ampli fication) is also improved. The treatment in the SAR micromixer is comparable lysis by long ultrasound exposure. Hence, SAR micromixer proved to be a good alternative method for cell lysis. Moreover, SAR micromixer has the advantage that it can easily be integrated into an automatic system for lysis and sample treatment. Article IV investigated the mixing performance at the outlet of SAR micromixer. The outlet channel of SAR micromixer was split into four sub-channels. Absorbance testing was used to implement to evaluate the outlet concentration of four subchannels. The homogeneous of fluids are varied with the inlet velocities. Article V presented the optimized fabrication process of the template of extremely long microneedles for blood extraction. Backside lithography with a UVlight source was employed to build the high aspect ratio SU-8-based microneedle template. Some major challenges on fabrication process were also shown and discussed in this article. Article VI covers a total process chain from design, fabrication to performance evaluation of the hollow microneedle design. The contribution of this article is a highly applicable theoretical model for the microneedle geometry. The proposed model has been developed to predict the fracture forces. A good agreement was observed between the results obtained from analytical solution and practical measurements of fracture force

Mixing-Performance Evaluation of a Multiple Dilution Microfluidic Chip for a Human Serum Dilution Process

This paper is aimed to propose a numerically designed multiple dilution microfluidic chip that can simultaneously deliver several serum dilutions in parallel. The passive mixing scheme is selected for dilution and achieved by the serpentine mixing channel in which Dean vortices are induced to increase the contact area and time for better diffusion. The mixing performance at the exit of this dilution chip is numerically evaluated using five commonly-used mixing indices with the goal that the homogeneity of the mixture over the exit cross-sectional area of the mixing channel must be greater than 93.319% to fulfill the six-sigma quality control

Numerical and experimental characterization of a novel modular passive micromixer

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (μLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice

Experimental and numerical investigations of novel passive micromixers using u-IF

Micromixers are indispensable components in Lab-on-a-Chip and micro total analysis systems (o-TAS). Typical micromixer applications include the mixing of reagents prior to chemical or biological reactions, drug delivery, medical diagnostics through biological sampling, and DNA sequencing or synthesis. The objective of the present investigation is to develop novel passive microfluidic mixers, which integrate mixing mechanisms of lamination and chaotic advection, through planar channel designs. Lamination is incorporated through repeated separation and combination of the mixing streams, while chaotic advection is implemented through serpentine mixing channels and barriers in the flow. The design includes three innovative in-plane on-chip functional micromixers, of channels ranging in width from 0.05 to 0.2 mm, a constant depth of 0.2 mm, and an overall mixer length of 5 mm. An experimental analysis was carried out to evaluate the mixing performance of the designed mixers. The working fluid is distilled water, with one stream mixed with commercial fluorescence dye. Micro Induced Fluorescence (o-IF) is used to quantitatively measure instant whole-field concentration distribution in the channels. Images along the axial length of the micromixers were recorded to quantify the mixing performance, over a Reynolds range of 1 to 100, a Péclet range from 10 3 to 105 , at a Schmidt number in the vicinity of 103 . The mixing performance shows patterns similar to the Taylor dispersion, which consists of both diffusion and convection. Compared to the designs available in literature, the present micromixers have achieved better mixing efficiency up to 95% with a pressure drop of 20 kPa in a mixing length of 5 mm at 1 {601} Re {601} 100. The experimental mixing performance is compared with the simulated results, as well as existing experimental data for different designs within the working Reynolds range. The experimental results show a reasonably good correlation with the simulated result

Design and development of a microfluidic platform for use with colorimetric gold nanoprobe assays

Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio (~13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 8l on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration below the limit of detection of the conventionally used microplate reader (i.e. 15 ng/μl) with 10 times lower solution volume (3 μl). The combination of the unique optical properties of gold nanoprobes with microfluidic platform resulted in sensitive and accurate sensor for single nucleotide polymorphism detection operating using small volumes of solutions and without the need for substrate functionalization or sophisticated instrumentation. Simultaneously, to enable on chip reagents mixing, a PDMS micromixer was developed and optimized for the highest efficiency, low pressure drop and short mixing length. The optimized device shows 80% of mixing efficiency at Re = 0.1 in 2.5 mm long mixer with the pressure drop of 6 Pa, satisfying requirements for the application in the microfluidic platform for DNA analysis.Portuguese Science Foundation - (SFRH/BD/44258/2008), “SMART-EC” projec