Optimized Simulation and Validation of Particle Advection in Asymmetric Staggered Herringbone Type Micromixers

This paper presents and compares two different strategies in the numerical simulation of passive microfluidic mixers based on chaotic advection. In addition to flow velocity field calculations, concentration distributions of molecules and trajectories of microscale particles were determined and compared to evaluate the performance of the applied modeling approaches in the proposed geometries. A staggered herringbone type micromixer (SHM) was selected and studied in order to demonstrate finite element modeling issues. The selected microstructures were fabricated by a soft lithography technique, utilizing multilayer SU-8 epoxy-based photoresist as a molding replica for polydimethylsiloxane (PDMS) casting. The mixing processes in the microfluidic systems were characterized by applying molecular and particle (cell) solutions and adequate microscopic visualization techniques. We proved that modeling of the molecular concentration field is more costly, in regards to computational time, than the particle trajectory based method. However, both approaches showed adequate qualitative agreement with the experimental results

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

Analysis, Design and Fabrication of Micromixers, Volume II

Micromixers are an important component in micrototal analysis systems and lab-on-a-chip platforms which are widely used for sample preparation and analysis, drug delivery, and biological and chemical synthesis. The Special Issue "Analysis, Design and Fabrication of Micromixers II" published in Micromachines covers new mechanisms, numerical and/or experimental mixing analysis, design, and fabrication of various micromixers. This reprint includes an editorial, two review papers, and eleven research papers reporting on five active and six passive micromixers. Three of the active micromixers have electrokinetic driving force, but the other two are activated by mechanical mechanism and acoustic streaming. Three studies employs non-Newtonian working fluids, one of which deals with nano-non-Newtonian fluids. Most of the cases investigated micromixer design

Development of a COMSOL Microdialysis Model, Towards Creation of Microdialysis on a Chip with Improved Geometries and Recovery

Microdialysis (µD) sampling is a diffusion-limited sampling method that has been widely used in different biomedical fields for greater than 35 years. Device calibration for in vivo studies is difficult for current non-steady state analytes of interest correlated with both inflammatory response and microbial signaling molecules (QS); which exist in low ng/mL to pg/mL with molecular weights over a wide range of 170 Da to 70 kDa. The primary performance metric, relative recovery (RR), relating the collected sample to the extracellular space concentration varies from 10% to 60% per analyte even under controlled bench-top conditions. Innovations in microdialysis device design have not deviated or improved upon the commercially-available cylindrical geometry for over 35 years. COMSOL Multiphysics finite element method (FEM) software was used to iteratively model and refine microfluidic-based (µF) µD device designs with the primary focus on optimizing channel geometry for improved RR. The primary focus was to improve fluid to membrane perimeter (P) to fluid cross-sectional area (A) and alter the concentration boundary layer (CBL) using passive µF mixing; which are not possible to fabricate using cylindrical geometries. The current µF µD design uses a simple asymmetric linear-looped (LL) geometry optimized with a P/A of 20 vs. 16.4 for a commercial CMA 20 µD probe with an equal 10 mm length. The simulated LL µF µD achieves a 16.1% relative increase in RR vs. experimental data at a 1.0 µL/min inlet flow rate using a 10 kDa FITC-labeled dextran as the analyte. Mixing was implemented and simulated using a modified herringbone geometry (HBM) and compared to an equivalent linear channel (LC). The HBM is shown to shift the CBL and increase diffusive flux at the membrane-fluid interface resulting in a 16.9 ± 0.7% relative increase in RR for 7 flow rates ranging from 0.125 to 2.0 µL/min vs. the LC. The combination of these changes is shown to increase RR above what is currently commercially available

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP : a case study using protein-loaded liposomes

Nanomedicines are well recognised for their ability to improve therapeutic outcomes. Yet, due to their complexity, nanomedicines are challenging and costly to produce using traditional manufacturing methods. For nanomedicines to be widely exploited, new manufacturing technologies must be adopted to reduce development costs and provide a consistent product. Within this study, we investigate microfluidic manufacture of nanomedicines. Using protein-loaded liposomes as a case study, we manufacture liposomes with tightly defined physico-chemical attributes (size, PDI, protein loading and release) from small-scale (1 mL) through to GMP volume production (200 mL/min). To achieve this, we investigate two different laminar flow microfluidic cartridge designs (based on a staggered herringbone design and a novel toroidal mixer design); for the first time we demonstrate the use of a new microfluidic cartridge design which delivers seamless scale-up production from bench-scale (12 mL/min) through GMP production requirements of over 20 L/h using the same standardised normal operating parameters. We also outline the application of tangential flow filtration for down-stream processing and high product yield. This work confirms that defined liposome products can be manufactured rapidly and reproducibly using a scale-independent production process, thereby de-risking the journey from bench to approved product

Experimental and Numerical Investigation of Mass Transfer in Passive Scaled-up Micromixers

Micromixers are vital components in micro-total analysis systems (μ-TAS) and Lab-on-Chip (LOC) devices, with applications in drug delivery, medical diagnostics, and chemical analyses, amongst others. Traditional macroscale mixing techniques may not be applied at the microscale, where viscous forces become important compared to inertial forces. As such, it remains a challenge to effectively and thoroughly mix liquid species in small characteristic dimensions. The present work aims to analyze flow phenomena and mass transfer in three novel scaled-up micromixers, which make use of variations in channel geometry to induce mixing. Designs based on multi-lamination inlets, obstruction filled channels, Dean vortex inducing curved channels, and helical flow inducing grooves are investigated. Flow visualization is used as a qualitative tool, providing valuable information regarding flow patterns and mixing. Induced fluorescence is applied to assess whole field concentration distribution, and provide quantitative species distribution data. Complex three dimensional flows are analyzed using numerical simulations, which show good agreement with experimental work. The mixers are evaluated over Reynolds numbers ranging from 0.5 to 100, corresponding to Péclet numbers ranging from 1.25 × 103 to 1.25 × 105. Results show a decreasing-increasing trend in the degree of mixing with increasing Reynolds number, as the dominant mixing mechanism changes from mass diffusion to mass advection. Up to 90% mixing is reported. To allow for reasonable mixing performance comparison with published work, an equivalent length parameter is proposed. The present devices offer good mixing in shorter lengths over a wide range of Reynolds numbers compared to numerous published devices

Magnetic bead-based DNA extraction and purification microfluidic chip

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.A magnetic bead-based DNA extraction and purification device has been designed to be used for extraction of the target DNA molecules from whole blood sample. Mixing and separation steps are performed using functionalised superparamagnetic beads suspended in the cell lysis buffer in a circular chamber that is sandwiched between two electromagnets. Non-uniform nature of the magnetic field causes temporal and spatial distribution of the beads within the chamber. This process efficiently mixes the lysis buffer and whole blood in order to extract DNA from target cells. Functionalized surface of the magnetic beads then attract the exposed DNA molecules. Finally, DNA-attached magnetic beads are attracted to the bottom of the chamber by activating the bottom electrode. DNA molecules are extracted from the magnetic beads by washing and re-suspension processes. The numerical simulation approach has been adopted in order to design the magnetic field source. The performance of the magnetic field source has been investigated against different physical and geometrical parameters and optimised dimensions are obtained with two different magnetic field sources; integrated internal source and external source. A new magnetic field pattern has been introduced in order to efficiently control the bulk of magnetic beads inside the mixing chamber by dynamic shifting of magnetic field regions from the centre of the coils to the outer edge of the coils and vice versa. A Matlab code has been developed to simulate beads trajectories inside the designed extraction chip in order to investigate the efficiency of the magnetic mixing. A preliminary target molecule capturing simulation has also been performed using the simulated bead trajectories to evaluate the DNA-capturing efficiency of the designed extraction chip. The performance of the designed extraction chip has been tested by conducting a series of biological experiments. Different magnetic bead-based extraction kits have been used in a series of preliminary experiments in order to extract a more automation friendly extraction protocol. The efficiency of the designed device has been evaluated using the spiked bacterial DNA and non-pathogenic bacterial cell cultures (B. subtilis, Gram positive bacteria and E. coli, Gram negative bacteria) into the blood sample. Excellent DNA yields and recovery rates are obtained with the designed extraction chip through a simple and fast extraction protocol