Interference Modeling and Capacity Analysis for Microfluidic Molecular Communication Channels

Shear stress, pressure, and flow rate are fluid dynamic parameters that can lead to changes in the morphology, proliferation, function, and survival of many cell types and have a determinant impact on tissue function and viability. Microfluidic devices are promising tools to investigate these parameters and fluid behaviour within different microchannel geometries. This study discusses and analyses different designed microfluidic channel geometries regarding the influence of fluid dynamic parameters on their microenvironment at specified fluidic parameters. The results demonstrate that in the circular microchamber, the velocity and shear stress profiles assume a parabolic shape with a maximum velocity occurring in the centre of the chamber and a minimum velocity at the walls. The longitudinal microchannel shows a uniform velocity and shear stress profile throughout the microchannel. Simulation studies for the two geometries with three parallel microchannels showed that in proximity to the micropillars, the velocity and shear stress profiles decreased. Moreover, the pressure is inversely proportional to the width and directly proportional to the flow rate within the microfluidic channels. The simulations showed that the velocity and wall shear stress indicated different values at different flow rates. It was also found that the width and height of the microfluidic channels could affect both velocity and shear stress profiles, contributing to the control of shear stress. The study has demonstrated strategies to predict and control the effects of these forces and the potential as an alternative to conventional cell culture as well as to recapitulate the cell- and organ-specific microenvironment.

Molecular communication is a bioinspired communication that enables macro-scale, micro-scale and nano-scale devices to communicate with each other. The molecular communication system is prone to severe signal attenuation, dispersion and delay, which leads to performance degradation as the distance between two communicating devices increases. To mitigate these challenges, relays are used to establish reliable communication in microfluidic channels. Relay assisted molecular communication systems can also enable interconnection among various entities of the lab-on-chip for sharing information. Various relaying schemes have been proposed for reliable molecular communication systems, most of which lack practical feasibility. Thus, it is essential to design and develop relays that can be practically incorporated into the microfluidic channel. This paper presents a novel design of passive in-line relay for molecular communication system that can be easily embedded in the microfluidic channel and operate without external energy. Results show that geometric modification in the microfluidic channel can act as a relay and restore the degraded signal up-to 28%.

The importance of biosensors based on optical fiber (OF) technology is increasing due to their high sensitivity and compatibility with minimally invasive real-time diagnostics and enormous potentials for in vivo biopsies. This study investigates the technical aspects behind integrating Lab-on-Tip optrodes within microfluidic channels, which is propaedeutic for guidelines setting towards their correct connection with minimally invasive clinical tools such as needles, catheters and nanoendoscopes. Here, as proof of concept, we investigated the integration of a plasmonic Metasurface-assisted Lab-on-Tip optrode, realized onto a single mode OF tip (OFMT), into a T-shaped microfluidic chip for the detection of a clinically relevant target molecule as the breast cancer biomarker receptor tyrosine protein kinase (ErbB2). The biosensor response to different ErbB2 concentrations (1–1000 ng/mL) was analyzed under controlled flow conditions. Experiments demonstrated a strong dependence of the detection performance on the probe position within the microfluidic channel, with increased performance frustration as the distance of the tip from the center is reduced. These findings, confirmed by numerical modeling, revealed an inverse relationship between the flow velocity and the biosensor performance. This relationship was further corroborated by additional experiments demonstrating that higher flow rates reduce the target molecule capability to correctly recognize the bioreceptor immobilized on the sensor surface due to the shorter analyte-probe interaction time. In summary, the present study highlights the importance of a multi-aspect microfluidics design considering local flow conditions for optimal probe placement, providing valuable guidelines for improving detection capabilities of microfluidic assisted Lab-on-Tip biosensing platforms for biomedical applications. • A Lab-on-Tip plasmonic optrode was integrated in a microfluidic chip to detect ErbB2. • The probe position in the channel and the flow rate affect the detection performance. • The biosensor response to different ErbB2 concentrations (1–1000 ng/mL) was analyzed.

A numerical study on differences in using Navier–Stokes and Reynolds equations for modeling the fluid flow and particle transport in single rock fractures with shear

Constant extension rate tensile (CERT) tests are traditionally used to understand the influence of material composition, heat treatment, temperature and environmental variables on stress corrosion crack (SCC) initiation. However, fluid flow rate has not been investigated as a parameter that could affect SCC initiation until recently. These studies have exhibited longer time to failure under high flow conditions indicating delayed crack initiation. Because these experiments have been performed in highly oxygenated water, no correlation has been established between the influence of flow velocity on the electrochemical corrosion potential (ECP) and the time to failure of tensile test specimens. The interrelationship between the fluid flow velocity, ECP and the time to failure is of great interest to the Boiling Water Reactor (BWR) applications primarily because of the previous observations that the ECP of Type 304 stainless steel increases with fluid flow velocity. This paper describes an attempt that has been made to understand the interrelationship between fluid flow velocity, ECP and the time for crack initiation in high temperature high purity water simulating both the BWR chemistry and the component flow velocity conditions. The range of flow velocities employed in the present study was 0.002 to 2 ft/s. The studies indicate that while high flow velocities can increase ECP there is a delayed effect on crack initiation.

Objectives. The development of microfluidic systems is one of the promising areas of science and technology. In most procedures performed using microfluidic systems, effective mixing in microfluidic channels of microreactors (chips) is of particular importance, because it has an effect on the sensitivity and speed of analytical procedures. The aim of this study is to describe and evaluate the major parameters of the flow and mixing processes in a passive microfluidic micromixer, and to develop an information-measuring system to monitor the dynamics of flow (mixing) of liquids.Methods. This article provides an overview of the concept of microfluidic mixing chips (micromixers) and their classification, and analyzes the kinds of points of mixing and microfluidic channels for mixing. The article presents the description and calculations of the hydrodynamic similarity criteria (Reynolds, Dean and Peclet numbers), which are the critical parameters for creating and optimizing micromixers (for example, straight and curved channels in the flow rate range between 100 and 1000 µl/min). We have developed an information-measuring system to monitor the dynamics of flow (mixing) of liquids in a microfluidic channel, which consists of a microscope with a digital eyepiece (LOMO MIB, Russia), an Atlas syringe pump (Syrris Ltd., UK) and a passive mixing microfluidic chip of interest (made of clear glass). This system was designed to quickly illustrate the principles of mixing in microfluidic channels of different configurations.Results. The developed system has allowed carrying out a colorimetric analysis of the modes and dynamics of mixing two liquids (5% aqueous solution of azorubine dye and water) at the T-shaped mixing point, at the straight and curved (double-bend shaped) sections of the microfluidic channel of the passive-type micromixer with flow rates varying from 100 to 400 µl/min.Conclusions. According to the obtained calculations, the share of the advective mixing processes (formation of vortex flows and increase in the contact area of the mixed substances) in flowing liquids is significantly higher in curved microchannels. The developed information-measuring system to monitor the dynamics of flow (mixing) of liquids in a microfluidic channel is a convenient tool for optimizing the mixing modes in the channels of micromixers, and for designing new configurations of channels in microchips. It would allow intensifying processes and increasing the performance of microfluidic systems.

We discuss, in this article, the solution method of the unsteady electroosmotic flow of Newtonian fluid in a square microfluidic channel cross-section in the framework of spreadsheet analysis. We demonstrate the implementation of the finite difference scheme, which is used for the discretization of the transport equations governing the flow dynamics of the present problem, in the spreadsheet tool. Also, we have shown the implementation details of different boundary conditions, which are typically used for the underlying electrohydrodynamics in a microfluidic channel, in the spreadsheet analysis tool. We show that the results obtained from the spreadsheet analysis match accurately with the numerical solutions for both the electrostatic potential distribution and the flow velocity. Our results of this analysis justify the credibility of the spreadsheet tool for capturing the intricate details of the electrically actuated microflows during the initial transiences, that is, for the start-up flows and the phenomenon due to the electrical double layer effect, quite effectively. The inferences of this analysis will open up a new research paradigm of microfluidics and microscale transport processes by providing the potential applicability of the spreadsheet tools to obtain the flow physics of our interest in a very intuitive and less expensive manner.

We demonstrate the dynamic coloration of polymerized cholesteric liquid crystal (PCLC) networks templated by the “wash-out/refill” method in the presence of organic compounds. The reflection colors were modulated by two key approaches, that is, the injection of mutually soluble organic fluids into a microfluidic channel and the diffusion of volatile organic compounds (VOCs). The reversible tuning of reflected colors with central wavelengths between ∼450 nm and ∼600 nm was achieved by alternative injection of nematic liquid crystal E7 (nav = 1.64) and benzyl alcohol (n = 1.54) using syringe pumps. The fascinating iridescence with reflection centers from ∼620 nm to ∼410 nm was presented from the volatilization and diffusion of alcohol as a model VOC. Additionally, the flow velocity of fluid and the diffusion time were adjusted to explore the underlying mechanism for the dynamic coloration of cholesteric networks. This work is expected to extend the study of PCLCs as a dynamically tunable optofluidic reflector, visually readable sensor, or compact anti-counterfeit label in response to organic compounds.

Liquid filling in microfluidic channels is a complex process that depends on a variety of geometric, operating, and material parameters such as microchannel geometry, flow velocity∕pressure, liquid surface tension, and contact angle of channel surface. Accurate analysis of the filling process can provide key insights into the filling time, air bubble trapping, and dead zone formation, and help evaluate trade-offs among the various design parameters and lead to optimal chip design. However, efficient modeling of liquid filling in complex microfluidic networks continues to be a significant challenge. High-fidelity computational methods, such as the volume of fluid method, are prohibitively expensive from a computational standpoint. Analytical models, on the other hand, are primarily applicable to idealized geometries and, hence, are unable to accurately capture chip level behavior of complex microfluidic systems. This paper presents a parametrized dynamic model for the system-level analysis of liquid filling in three-dimensional (3D) microfluidic networks. In our approach, a complex microfluidic network is deconstructed into a set of commonly used components, such as reservoirs, microchannels, and junctions. The components are then assembled according to their spatial layout and operating rationale to achieve a rapid system-level model. A dynamic model based on the transient momentum equation is developed to track the liquid front in the microchannels. The principle of mass conservation at the junction is used to link the fluidic parameters in the microchannels emanating from the junction. Assembly of these component models yields a set of differential and algebraic equations, which upon integration provides temporal information of the liquid filling process, particularly liquid front propagation (i.e., the arrival time). The models are used to simulate the transient liquid filling process in a variety of microfluidic constructs and in a multiplexer, representing a complex microfluidic network. The accuracy (relative error less than 7%) and orders-of-magnitude speedup (30 000X-4 000 000X) of our system-level models are verified by comparison against 3D high-fidelity numerical studies. Our findings clearly establish the utility of our models and simulation methodology for fast, reliable analysis of liquid filling to guide the design optimization of complex microfluidic networks.

Light-addressable potentiometric sensor (LAPS) is a kind of semiconductor sensor based on electrolyte-insulating -semiconductor (EIS) structure that is sensitive to surface potential. Due to the light-addressability, it can record the photocurrent signals point to point where the modulated laser beam focused on. Cells encapsuled in hydrogel scaffold to constructed the 3D cell model can form chemical and oxygen gradient thus causing different metabolism state in different spatial position. In this study, a partial thinned Si 3 N 4 -LAPS chip integrated with microfluidic channel has been constructed for real-time 3D cell metabolism state monitoring. HepG2 cells are encapsulated in hydrogel to construct 3D liver cancer model. The system consists of sensing component, optical component, precision electronically controlled stage and a homemade software based on LabVIEW. In the bioreactor, cells take in high-glucose medium to secrete acidic metabolites, which leads to a decrease in photocurrent dramatically. With the help of this system, real-time visualization of cell metabolic dynamic process can be achieved. Moreover, medium or anti-cancer drugs can be automatically delivered to the bioreactor with the assistance of microfluidic technology to carry out cell culture and drug efficacy evaluation. This high-resolution photoelectrochemical imaging system has potential to achieve long-term drug screening platform. Key words Light-addressable potentiometric sensor, 3D cell model, chemical gradient, cell metabolic visualization, drug screening Introduction Cellular metabolism is one of the most basic physiological functions of cells to maintain viability. Cells absorb and decompose various nutrients to produce energy necessary for proliferation and differentiation, while secreting acidic metabolites. Glucose, as the main nutrition source of cells, will be decomposed into energy and acidic substance under both aerobic and anaerobic conditions. The acidic products (such as carbon dioxide, lactic acid) will cause the pH decrease in the extracellular microenvironment. Therefore, the extracellular acidification rate (ECAR) can be used to characterized the cellular metabolic level. Nowadays, three-dimensional cell culture model has attracted the attentions of researchers, which can maintain more physiologically relevant microenvironment resemble to in vivo . Among all these models, 3D cell culture integrated with microfluidic chip has the unique advantages to recapitulating the cell microenvironment. Nevertheless, there exists general problems (oxygen concentration, chemical gradient) due to the special property of 3D cell model.Traditional ECIS and MEA system can not detect the spatial distribution of extracellular acidification rate,but laser beam could be focused and irradiated on the designated LAPS area to realize the light-addressable function based on the characteristics of LAPS. So,scanning the light spot along the chip can obtain spatial distribution of current signal to solve this problem. Method Si 3 N 4 -LAPS chip and backside illumination method were adopted with backside-thinned was thinned. The thickness of the silicon substrate is 500 μm, and the central area is thinned to 100 μm (Fig.1B) to reduce the lateral diffusion of carriers in the semiconductor layer and improve the sign-to-noise ratio while providing sufficient mechanical support. Before seeding cells, the LAPS chip was cleaned by deionized water, sterilized by UV and 75% ethanol, and incubated with 5 μg/mL gelatin at 4 °C overnight to improve the adhesion ability to cells. HepG2 cells were cultured in DMEM medium with 10% FBS, 100 U/ml Penicillin and 100 mg/ml Streptomycin. Then cells suspended in the medium were mixed in matrigel and cross-linked in a 37 °C humidified incubator with 5% CO 2 for 30 minutes. Drug test is conducted by doxorubicin. The stage performed grid scanning. In the X-axis direction, the resolution is determined by the stepping distance, and in the Y-axis direction, the motor keeps continuously moving, and the signal is continuously collected. The spatial resolution is determined by the movement rate and the sampling rate. Results and Conclusions In order to maintain highly stability of the optical lens group, the optical path is fixed and the sensing chip can move with the stage; the chip is mounted on the stage by an adjustable fixing scaffold, and the laser reflector is fixed on an immovable base. The 680 nm red light emitted by the laser diode is transmitted through a multi-mode fiber and collimated by fiber collimator, then irradiated on the back of the chip from the vertical direction through an aspheric lens (Figure1A). The horizontal resolution, which was consistent with motor, was step set to 50 μm. The motor speed is 2.5mm/s, the sampling rate is 50k/S, the number of samples per pixel is 2000. The obtained real-time current grayscale image is shown in Figure 1C. The white part (high current value) is the thinning area of the chip, that is, the effective sensitive area; the black part is the non-thinning area, and the gray is the intermediate transition area. The converted pseudo-color image is shown in Figure 1D. The number of pixels of the image is 142×128, and the actual size is 6mm×6mm, indicating that this LAPS scanning imaging system can obtain an imaging resolution of less than 50 μm. Hanging drop method was conducted to achieve cell 3D culture. The microscope brightfield image of 3D HepG2 cell sphere is shown in figure 1E and green fluorescence image is shown in figure 1F. Then 3D cell sphere were seeded into microfluidic LAPS chip to realize real-time visualization of cell metabolism. Figure 1

We have developed hybrid femtosecond laser processing for fabrication of 3D microfluidic SERS chips. The resulting chip can perform the real-time SERS detection of Cd2+ ions at concentrations as low as 10 ppb. We have further proposed a novel strategy by taking advantage of the microfluidic configuration. The microfluidic chip can produce an interface of analyte solution and air on the SERS substrate in the microfluidic channel, which locally aggregates the analyte molecules at the interface during the measurements (LI-SERS). The LI-SERS technique achieves the analytical enhancement factor reaching 1.5 × 10^14 with a detection limit below 10 aM.

Isolation of exosome from culture medium in an effective way is desired for a less time consuming, cost saving technology in running the diagnostic test on cancer. In this study, we aim to develop an inertial microfluidic channel to separate the nano-size exosome from C666-1 cell culture medium as a selective sample. Simulation was carried out to obtain the optimum flow rate for determining the dimension of the channels for the exosome separation from the medium. The optimal dimension was then brought forward for the actual microfluidic channel fabrication, which consisted of the stages of mask printing, SU8 mould fabrication and ended with PDMS microchannel curing process. The prototype was then used to verify the optimum flow rate with polystyrene particles for its capabilities in actual task on particle separation as a control outcome. Next, the microchip was employed to separate the selected samples, exosome from the culture medium and compared the outcome from the conventional exosome extraction kit to study the level of effectiveness of the prototype. The exosome outcome from both the prototype and extraction kits were characterized through zetasizer, western blot and Transmission electron microscopy (TEM). The microfluidic chip designed in this study obtained a successful separation of exosome from the culture medium. Besides, the extra benefit from this microfluidic channels in particle separation brought an evenly distributed exosome upon collection while the exosomes separated through extraction kit was found clustered together. Therefore, this work has shown the microfluidic channel is suitable for continuous separation of exosome from the culture medium for a clinical study in the future.

We have developed a fast and simple method for fabricating microfluidic channels in silicon using direct laser writing. The laser microfabrication process was optimised to generate microfluidic channels with vertical walls suitable for acoustic particle focusing by bulk acoustic waves. The width of the acoustic resonance channel was designed to be 380 µm, branching into a trifurcation with 127 µm wide side outlet channels. The optimised settings used to make the microfluidic channels were 50% laser radiation power, 10 kHz pulse frequency and 35 passes. With these settings, six chips could be ablated in 5 h. The microfluidic channels were sealed with a glass wafer using adhesive bonding, diced into individual chips, and a piezoelectric transducer was glued to each chip. With acoustic actuation at 2.03 MHz a half wavelength resonance mode was generated in the microfluidic channel, and polystyrene microparticles (10 µm diameter) were focused along the centre-line of the channel. The presented fabrication process is especially interesting for research purposes as it opens up for rapid prototyping of silicon-glass microfluidic chips for acoustofluidic applications.

We have investigated a micro vapor membrane valve (MVMV) for closing the microfluidic channels by laser irradiation on carbon nanocoils (CNCs) attached to the inner wall of the microchannels. The microchannel with MVMVs was found to exhibit a "closed" state without the supply of laser energy, which is explained on the basis of the theory of heat and mass transfer. Multiple MVMVs for sealing the channels can be generated in sequence and exist simultaneously at different irradiation sites, independently. The significant advantages of the MVMV generated by the laser irradiation on CNCs are the elimination of extrinsic energy required to maintain the microfluidic channel "closed" state and the simplification of the structure integrated into the microfluidic channels and fluid control circuitries. The CNC-based MVMV is a powerful tool for the investigations of the functions of microchannel switching and sealing on microfluidic chips in biomedicine, chemical analysis and other fields. The study of MVMVs will have great significance for biochemical and cytological analysis.

We have developed a novel method to synthesize and integrate one dimensional nanostructures within microfluidic chip via hydrothermal reaction with the microchannel as a physical constraint. Precursor solution of metal oxide (ZnO) nanowire is flown through the microfluidic channel while the thermal energy is supplied either throughout the entire chip by heating plate or near selected regions by microscale metal heaters. This global or localized heating of ZnO precursor solution allows hydrothermal growth of ZnO nanowires and their in-situ integration within microfluidic channel. This novel method is expected to be used as a convenient route to the fabrication of nanostructure-based chemical / biological filters and electrodes for electrochemical sensors for microfluidic lab-on-a-chip systems.