ARTICLE | doi:10.20944/preprints201909.0061.v1
Subject: Engineering, Mechanical Engineering Keywords: slip flow; navier-slip boundary condition; hydrophobic microchannels; analytical solutions; poiseuille number; velocity profile of poiseuille flow
Online: 5 September 2019 (11:27:50 CEST)
Fluid mechanics of flow in hydrophobic, rectangular microchannels with finite aspect ratios is of paramount importance. In such microchannels, not only the effect of the side walls should be taken into account, but also the classical assumption of no-slip boundary condition (BC) is no longer valid at the solid-liquid interface. Accordingly, slip flow can occur in microchannels fabricated from surfaces with low wetting conditions, hydrophobic surfaces. Determining the interactions of liquid molecules adjacent to solid surface is still a challenging issue, and it is especially important in small scale domains. Herein, the fluid mechanics of flow through rectangular hydrophobic microchannels has been reconsidered by taking into account the general Navier-slip BCs at the solid-liquid interface. For fully developed incompressible flow in microchannels at low Reynolds number, partial differential equation (PDE) of the momentum equation simplifies to the classical Poisson equation. Accordingly, by analytically solving the Poisson equations with general Navier-slip BCs, the most general forms of velocity distributions, flow rate, friction factor and Poiseuille number have been obtained.
ARTICLE | doi:10.20944/preprints201905.0316.v1
Subject: Engineering, Mechanical Engineering Keywords: aspect ratio effects; velocity profile of poiseuille flow; friction factor; eigenfunction expansion technique; finite element method; 3D microchannels
Online: 27 May 2019 (12:32:24 CEST)
This study presents a new form of velocity distribution in laminar liquid flow in rectangular microchannels using the eigenfunction expansion technique. Darcy friction factor and Poiseuille number are also obtained analytically. Due to the symmetry of the solutions, the effects of changing the aspect ratio from 0 to ∞ are also discussed. Using finite element method (FEM), the obtained analytical results are further compared with the 3D numerical simulations for the rectangular microchannels with different range of aspect ratio and pressure gradient, and excellent agreements were found. These findings provide additional insights in interpreting the results of the pressure-driven flows in finite aspect ratio microchannels, in which very precise comparison with the macroscale theory is crucial.
REVIEW | doi:10.20944/preprints201806.0011.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: spheroid culture; microfluidic cell culture; spheroids on-chip; tumor microenvironment; in vitro cell culture
Online: 1 June 2018 (09:58:58 CEST)
Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumor models. The complex tumor microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.
REVIEW | doi:10.20944/preprints202109.0287.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: drug screening; monodrug or combinatorial drug screening; anti-cancer
Online: 16 September 2021 (13:46:49 CEST)
The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.
ARTICLE | doi:10.20944/preprints202106.0487.v1
Subject: Engineering, Automotive Engineering Keywords: Lab-On-Chip; Acoustic Microfluidics; Spheroid-On-Chip; Necrotic and hypoxic zones
Online: 18 June 2021 (15:25:21 CEST)
Microfluidic lab-on-chip devices are widely being developed for chemical and biological studies. One of the most commonly used types of these chips is perfusion microwells for culturing multicellular spheroids. The main challenge in such systems is the formation of substantial necrotic and hypoxic zones within the cultured spheroids. Herein, we propose a novel acoustofluidic integrated platform to tackle this bottleneck problem. We show that such an approach enhances cell viability and shrinks necrotic and hypoxic zones in these spheroid-on-a-chip platforms without the need to increase the flow rate, leading to a significant reduction in costly reagents' consumption. Proof-of-concept, designing procedures, and finite element numerical simulation are discussed in details. Also, the effects of acoustic and hydrodynamic parameters on the cultured cells are investigated. The results show that by increasing acoustic boundary displacement amplitude (d0), the spheroid’s proliferating zone enlarges greatly. Moreover, it is shown that by implementing d0=0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.
ARTICLE | doi:10.20944/preprints202109.0482.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: WBC isolation; Spiral microchannels; Inertial microfluidics; Passive cell separation; High-throughput separation
Online: 29 September 2021 (09:35:31 CEST)
Rapid isolation of white blood cells (WBCs) from whole blood is an essential part of any WBC examination platform. However, most conventional cell separation techniques are labor-intensive and low throughput, require large volumes of samples, need extensive cell manipulation, and have low purity. To address these challenges, we report the design and fabrication of a passive, label-free microfluidic device with a unique U-shaped cross-section to separate WBCs from whole blood using hydrodynamic forces that exist in a microchannel with curvilinear geometry. It is shown that the spiral microchannel with a U-shaped cross-section concentrates larger blood cells (e.g., WBCs) in the inner cross-section of the microchannel by moving smaller blood cells (e.g., red blood cells (RBCs) and platelets) to the outer microchannel section and preventing them from returning to the inner microchannel section. Therefore, it overcomes the major limitation of a rectangular cross-section where secondary Dean vortices constantly enforce particles throughout the entire cross-section and decrease its isolation efficiency. Under optimal settings, more than 95% of WBCs can be isolated from whole blood under high-throughput (6 ml/min), high-purity (88%), and high-capacity (180 ml of sample in 1 hour) conditions. High efficiency, fast processing time, and non-invasive WBC isolation from large blood samples without centrifugation, RBC lysis, cell biomarkers, and chemical pre-treatments make this method an ideal choice for downstream cell study platforms.
REVIEW | doi:10.20944/preprints202103.0720.v1
Subject: Engineering, Automotive Engineering Keywords: microneedle; microneedle array, interstitial fluid; bio sensing, wearable system; ISF sampling
Online: 30 March 2021 (09:55:02 CEST)
Dermal interstitial fluid (ISF) is a novel source of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment. Nevertheless, in vivo extraction and analysis of ISF are challenging. On the other hand, microneedle (MN) technology can address most of the challenges associated with dermal ISF extraction and is well-suited for long-term, continuous ISF monitoring as well as in situ detection. In this review, we first briefly summarise the different dermal ISF collection methods and compare them with MN methods. Next, we elaborate on the design considerations and biocompatibility of MNs. Subsequently, the fabrication technologies of various MNs used for dermal ISF extraction, including solid MNs, hollow MNs, porous MNs and hydrogel MNs, are thoroughly explained. In addition, different sensing mechanisms of ISF detection will be discussed in detail. Subsequently, we identify the challenges and propose the possible solutions associated with ISF extraction. A detailed investigation is provided for the transport and sampling mechanism of ISF in vivo. Also, the current in vitro skin model integrated with the MN arrays will be discussed. Finally, future directions to develop a point-of-care (POC) device to sample ISF are proposed.