Microfluidic Channel Structure Research Articles

Room temperature imprinting of water-based microparticulate inks for realizing glass microfluidic channels

The combination of imprinting and extrusion overprinting of composite glass materials offers a pathway for the fabrication of fully integrated functional microfluidic devices. Utilizing novel low-temperature phosphate glasses, originally developed for 3D extrusion printing, imprinting now has been achieved with soft stamps. The current hybrid process demonstrates superior resolution compared to previously reported extrusion techniques, presenting possibilities for applications such as open microfluidic channels that can subsequently be sealed by extrusion printing. The water-based microparticle glass-ink enables patterning at room temperature and its solidification occurring through water evaporation within the glass particle scaffold. Following the demolding, sintering is conducted at a temperature of 485 °C, resulting in dense glass elements with porosity levels below 1 %. For straightforward microfluidic channel structures featuring channels ranging from 100-200 µm in width, the shape is fully preserved during demolding and sequential annealing. The shrinkage observed is almost isotropic. The channels were successfully tested in an open microfluidic setup and initial tests were performed with the closed channels.

Development of eutectic gallium-indium-based transparent conductive electrodes on flexible substrates for touch sensor integration

In this study, the adaptability of liquid metal (LM)-based transparent conductive electrodes (TCEs) to flexible substrates and their potential applications in various electronics fields were investigated. To achieve this, conventional microfabrication techniques were employed to pattern polydimethylsiloxane (PDMS) channels and introduce an Eutectic Gallium-Indium (EGaIn) LM with the aim of enhancing transmittance and reducing sheet resistance. Microfluidic channel structures with varying pitch lengths and widths were fabricated in the types of grid patterns, labeled Pattern A (2000 μm pitch, 40 μm width), Pattern B (2000 μm pitch, 80 μm width), Pattern C (200 μm pitch, 40 μm width), and Pattern D (200 μm pitch, 80 μm width. The corresponding average transmittance values for the EGaIn LM-based TCE were 90 %, 71.8 %, 61.8 %, and 43.2 % for Patterns A, B, C, and D, respectively. To illustrate the potential in touch sensor applications, resistance changes in Patterns A, B, C, and D were assessed under applied forces ranging from 0 N to 150 N, revealing resistance changes of 0.0265 Ω, 0.03617 Ω, 0.03977 Ω, and 0.11629 Ω, respectively.

Machining technologies and structural models of microfluidic devices

In the past decades, microfluidic chips have been one of the hottest research topics in the “lab-on-a-chip” field. However, it is still a challenge for design the perfect microchannels with high functional integration, complex geometry, and high production efficiency. This review paper provides a comprehensive overview of microfluidic structural models and designs, manufacturing techniques, and bonding methods. The effect of three types of microfluidic channel structure models and their configuration parameters on the fluid behaviors of microfluidics was investigated. Surface-to-volume ratio of the flow channel is a critical parameter for determining the mixing and diffusion capabilities of the microfluidic devices (MDs). Thereafter, the main manufacturing techniques for microstructures were discussed, including etching, photolithography, soft lithography, molding, mechanical micro-machining, laser beam micromachining, printing, and 3D printing. We performed a statistical analysis to discuss the relative advantages and disadvantages of these manufacturing methods. In addition, the current bonding methods for MDs were also summarized, including thermal bonding, solution adhesive bonding, dry adhesive bonding, plasma bonding, and anodic bonding. a comparison of different bonding methods was presented to provide a reference to select a suitable bonding method for the assembly of microfluidic device. Finally, the tendencies and challenges of microchannel manufacturing were discussed, and the prospects were also provided.

A Study on Photocurable Liquid-Crystal-on-Silicon (LCoS) Microdisplay Based Stereolithography Type 3D Printer for Fabrication of Microfluidic Channel Systems

A microfluidics chip is a miniature analytical system that injects a small amount of reagent into microchannels formed in the chip. It controls fluid flow to perform pretreatment, detection, reaction, mixing, separation, and analysis in parallel. In this study, polygonal microchannel structures were fabricated using a microstereolithography 3D printer based on an LCoS microdisplay projector. In the experiment, the width of the microchannel structure was changed from 50 ㎛ to 500 ㎛, and the output and width of the structure were measured. Inspection of the shape of the resulting microchannel structure showed that the tip of the structure was elliptical instead of the expected rectangular shape, and the fabrication width error increased as the channel width decreased to 200 ㎛ or less. Nevertheless, it was possible to fabricate microfluidics chip structures with widths less than 100 ㎛. The results of this study demonstrate the applicability of an LCoS microdisplay project-based 3D printer for the fabrication of microfluidic channel structures.

Development of Low-Residual-Stress Photosensitive Adhesive Materials for Wafer-Scale Microfluidic Device Fabrication

We have previously developed a photosensitive adhesive material that enables microfluidic channel structure formation and subsequent bonding to a cover with the aim of simplifying the process of wafer-scale microfluidic device fabrication. However, the bonding process and a subsequent curing process required heat treatment at 200 ℃ and 180 ℃, respectively, resulting in the generation of relatively high residual thermal stress. This may lead to delamination, warping, and cracking depending on the application environment. Therefore, in the present study, we designed a new material platform in which the patterning, bonding, and curing processes are based on ultraviolet (UV) reaction of polyfunctional acrylate, tackiness of epoxy resin, and UV/thermal reaction of epoxy resin in order to achieve low residual stress through low-temperature processing. Proof of concept was conducted through the evaluation of various physical properties of the system and found that the new type of photosensitive adhesive material, which bonded to a cover and cured at lower temperatures of 100 ℃ and 120 ℃, respectively, had a low residual stress of 10 MPa and good insulation reliability. This is a promising material for applications such as cooling devices for semiconductor chips, where long-term reliability is required.

Compartmentalized organ-on-a-chip structure for spatiotemporal control of oxygen microenvironments

Hypoxia is a condition where tissue oxygen levels fall below normal levels. In locally induced hypoxia due to blood vessel blockage, oxygen delivery becomes compromised. The site where blood flow is diminished the most forms a zero-oxygen core, and different oxygenation zones form around this core with varying oxygen concentrations. Naturally, these differing oxygen microenvironments drive cells to respond according to their oxygenation status. To study these cellular processes in laboratory settings, the cellular gas microenvironments should be controlled rapidly and precisely. In this study, we propose an organ-on-a-chip device that provides control over the oxygen environments in three separate compartments as well as the possibility of rapidly changing the corresponding oxygen concentrations. The proposed device includes a microfluidic channel structure with three separate arrays of narrow microchannels that guide gas mixtures with desired oxygen concentrations to diffuse through a thin gas-permeable membrane into cell culture areas. The proposed microfluidic channel structure is characterized using a 2D ratiometric oxygen imaging system, and the measurements confirm that the oxygen concentrations at the cell culture surface can be modulated in a few minutes. The structure is capable of creating hypoxic oxygen tension, and distinct oxygen environments can be generated simultaneously in the three compartments. By combining the microfluidic channel structure with an open-well coculture device, multicellular cultures can be established together with compartmentalized oxygen environment modulation. We demonstrate that the proposed compartmentalized organ-on-a-chip structure is suitable for cell culture.

An addressable electrowetting valve for centrifugal microfluidics

Centrifugal microfluidic platforms aim to integrate and perform complex biological and chemical processes within disc-like substrates and valving through centrifugal forces and the Coriolis effect. Although the integration of active valves within such system can be used to enhance fluid control, the ability to fabricate and integrate addressable valves within centrifugal platforms remains a significant challenge. To address this issue, herein, we present and test an addressable electrowetting centrifugal (EWC) valve. The EWC valve comprises a hydrophobic burst valve, integrated side electrodes and a dielectric layer between the microfluidic channel and electrode structures. The burst valve is made from a hydrophobic material able hold a specified pressure. Specifically, application of an external electric field is used to alter the valve wettability, making the valve more hydrophilic, decreasing the threshold pressure and triggering the opening of the valve. To assess valve performance, we investigate the influence of electric properties and channel geometry on valve response and then demonstrate multiple operations on different fluid samples. Finally, and to highlight the utility of EWC valves, we demonstrate the detection and analysis of CD4 human immune cells.

Enhanced Electricity Generation from Graphene Microfluidic Channels for Self-Powered Flexible Sensors.

As a novel energy harvesting method, generating electricity from the interaction of liquid-solid interface has attracted growing interest. Although several functional materials have been carried out to improve the performance of the flow-induced hydrovoltaic generators, there are few reports on influencing the droplet flow behavior to excavate its electricity generation by governing the device structure. Here, the output performance of the graphene microfluidic channel (GMC) structure is ∼13 times higher than that of the flat-open space graphene morphology. The strong slip flow and high surface charge density near the graphene-droplet interface originate from the GMC structure, which produces an effective liquid-solid interaction and rapid relative movement of the droplet. Additionally, based on the GMC structure a self-powered pressure sensor is designed. The droplet motion is regulated by external forces to generate specific voltages, which provide a new approach for the development of wearable self-powered electronics.

In situ detection of fluid media based on a three-dimensional dendritic silver surface-enhanced Raman scattering substrate

A simple substitution reaction was used to grow 3D dendritic silver structures in microfluidic channels, and a highly active SERS detection platform was formed. The system can realize in situ detection of 10−10 mol L−1 R6G solution.

Characterization of Mixing Performance Induced by Double Curved Passive Mixing Structures in Microfluidic Channels

Functionalized sensor surfaces combined with microfluidic channels are becoming increasingly important in realizing efficient biosensing devices applicable to small sample volumes. Relaxing the limitations imposed by laminar flow of the microfluidic channels by passive mixing structures to enhance analyte mass transfer to the sensing area will further improve the performance of these devices. In this paper, we characterize the flow performance in a group of microfluidic flow channels with novel double curved passive mixing structures (DCMS) fabricated in the ceiling. The experimental strategy includes confocal imaging to monitor the stationary flow patterns downstream from the inlet where a fluorophore is included in one of the inlets in a Y-channel microfluidic device. Analyses of the fluorescence pattern projected both along the channel and transverse to the flow direction monitored details in the developing homogenization. The mixing index (MI) as a function of the channel length was found to be well accounted for by a double-exponential equilibration process, where the different parameters of the DCMS were found to affect the extent and length of the initial mixing component. The range of MI for a 1 cm channel length for the DCMS was 0.75–0.98, which is a range of MI comparable to micromixers with herringbone structures. Overall, this indicates that the DCMS is a high performing passive micromixer, but the sensitivity to geometric parameter values calls for the selection of certain values for the most efficient mixing.

Investigation of the Effect of Channel Structure and Flow Rate on On-Chip Bacterial Lysis.

Successful lysis of cells/microorganisms is a key step in the sample preparation in fields like molecular biology, bioengineering, and biomedical engineering. This study therefore aims to investigate the lysis of bacteria on-chip and its dependence on both microfluidic channel structure and flow rate. Effects of temperature on lysis on-chip were also investigated. To perform these investigations, three different microfluidic chips were designed and produced (straight, zigzag and circular configurations), while the length of the channels were kept constant. As an exemplary case, Mycobacterium smegmatis was chosen to represent the acid-fast bacteria. Bacterial suspensions of 1.5 McFarland were injected into the chips at various flow rates (0.6- [Formula: see text]/min) either at room temperature or 50° C. In order to understand the on-chip lysis performance fully, off-chip experiments were carried out at durations which are equal to those bacteria spent in the channel from inlet to the outlet at different flow rates. We also performed COMSOL multiphysics program simulations to evaluate further the effect of the applied parameters. As a result, we found that the structure and the flow rate do not affect lysis over all in all investigated channel types, however on-chip experiments at room temperature produced more effective lysis compared to the on-chip and the off-chip samples performed at higher temperatures. Interestingly on-chip experiments at higher tempratures do not result in effective lysis.

Analysis of resistance characteristics of liquid flow in microfluidic channels

In order to investigate the resistance characteristics of liquid flow in microfluidic channels, the mathematical models of liquid flow resistance in microfluidic channels are established in this paper. The microfluidic channel samples with different parameters are designed and fabricated by using soft lithography technology. The effects of channel parameters of channel aspect ratio α, channel equivalent diameter dl and channel length/diameter ratio l / dl on liquid flow resistance are analysed and tested through experiments. This paper reveals the flow resistance performances in microfluidic channels and provides research basis for improving the flow characteristics and optimizing the microfluidic channel structures.

Metre-per-second microfluidic flow velocimetry with dual beam optical coherence tomography.

A novel dual beam Optical Coherence Tomography (OCT) instrument has been developed for high velocity flow measurement, principally in microfluidics applications. The scanned dual beam approach creates a pair of image-frames separated by a small spatiotemporal offset. Metre-per-second flow measurement is achieved by rapid re-imaging by the second beam allowing for particle tracking between each image-frame of the pair. Flow at 1.06 m/s using a single optical access port has been measured, more than two orders of magnitude larger than previously reported OCT systems, at centimetre depth and with millimetre scale depth of field within a microfluidic chip, whilst simultaneously imaging the microfluidic channel structure.

Ultrasensitive dual probe immunosensor for the monitoring of nicotine induced-brain derived neurotrophic factor released from cancer cells

Brain-derived neurotrophic factor (BDNF) was detected in the extracellular matrix of neuronal cells using a dual probe immunosensor (DPI), where one of them was used as a working and another bioconjugate loading probe. The working probe was fabricated by covalently immobilizing capture anti-BDNF (Cap Ab) on the gold nanoparticles (AuNPs)/conducting polymer composite layer. The bioconjugate probe was modified by drop casting a bioconjugate particles composed of conducting polymer self-assembled AuNPs, immobilized with detection anti-BDNF (Det Ab) and toluidine blue O (TBO). Each sensor layer was characterized using the surface analysis and electrochemical methods. Two modified probes were precisely faced each other to form a microfluidic channel structure and the gap between inside modified surfaces was about 19 µm. At optimized conditions, the DPI showed a linear dynamic range from 4.0 to 600.0 pg/ml with a detection limit of 1.5 ± 0.012 pg/ml. Interference effect of IgG, arginine, glutamine, serine, albumin, and fibrinogene were examined and stability of the developed biosensor was also investigated. The reliability of the DPI sensor was evaluated by monitoring the extracellular release of BDNF using exogenic activators (ethanol, K+, and nicotine) in neuronal and non-neuronal cells. In addition, the effect of nicotine onto neuroblastoma cancer cells (SH-SY5Y) was studied in detail.

Detection of Ca2+-induced acetylcholine released from leukemic T-cells using an amperometric microfluidic sensor

A microfluidic structured-dual electrodes sensor comprising of a pair of screen printed carbon electrodes was fabricated to detect acetylcholine, where one of them was used for an enzyme reaction and another for a detection electrode. The former was coated with gold nanoparticles and the latter with a porous gold layer, followed by electropolymerization of 2, 2:5,2-terthiophene-3-(p-benzoic acid) (pTTBA) on both the electrodes. Then, acetylcholinesterase was covalently attached onto the reaction electrode, and hydrazine and choline oxidase were co-immobilized on the detection electrode. The layers of both modified electrodes were characterized employing voltammetry, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and quartz crystal microscopy. After the modifications of both electrode surfaces, they were precisely faced each other to form a microfluidic channel structure, where H2O2 produced from the sequential enzymatic reactions was reduced by hydrazine to obtain the analytical signal which was analyzed by the detection electrode. The microfluidic sensor at the optimized experimental conditions exhibited a wide dynamic range from 0.7nM to 1500μM with the detection limit of 0.6 ± 0.1nM based on 3s (S/N = 3). The biomedical application of the proposed sensor was evaluated by detecting acetylcholine in human plasma samples. Moreover, the Ca2+-induced acetylcholine released in leukemic T-cells was also investigated to show the in vitro detection ability of the designed microfluidic sensor. Interference due to the real component matrix were also studied and long term stability of the designed sensor was evaluated. The analytical performance of the designed sensor was also compared with commercially available ACh detection kit.

Highly Sensitive Metabolite Biosensor Based on Organic Electrochemical Transistor Integrated with Microfluidic Channel and Poly(N‐vinyl‐2‐pyrrolidone)‐Capped Platinum Nanoparticles

Organic electrochemical transistors (OECTs) are used as highly sensitive glucose and lactate sensors by modifying the gate electrode with glucose oxidase/lactate oxidase and poly(n‐vinyl‐2‐pyrrolidone)‐capped platinum nanoparticles (Pt NPs). The Pt NPs are deposited by using a two‐step dip coating method without bias instead of the conventional electrodeposition method and followed by an UV‐Ozone post treatment to enhance the catalytic ability of the Pt NPs. The modified OECT sensors have extremely high sensitivity, and can achieve a detection limit of glucose and lactate down to 10−7 and 10−6m, respectively. A polydimethylsiloxane microfluidic channel is successfully integrated with the OECT sensors, which provides a compact chip size of the sensors, a short detection time of around 1 min and extremely low consumption of analyte (30 L). The cross talk between individual sensors in multianalyte sensing devices is also reduced by the dual microfluidic channel structure. Practical applications, such as for detecting glucose in saliva, can therefore be realized, and a prototype of a portable glucose sensor has been successfully created in this study. This portable glucose sensor has excellent potential for real‐time and noninvasive glucose sensing applications.

Fabrication of LTCC Micro-fluidic Devices For Wireless Lab-On-A-Chip Applications

Abstract Low temperature co-fired ceramic (LTCC) based microfluidic sensors have been developed for biomedical and environmental sensing systems. This paper introduces a microfluidic chamber based on impedance spectroscopy measurements using LTCC technology for wireless Lab-On-A-Chip (LOC) applications. To overcome the channel sagging during the fabrication process, we used sacrificial carbon tapes as solid inserts, thus guiding the LTCC to follow their shape upon lamination and then formed micro-channels. The measurement chamber was a parallel-plate capacitive structure with 85 μm gap. This platform requires a small fluid sample of less than 4 μL. The sensor formed by the microfluidic channel and capacitance structure was characterized using different dielectric materials such as air, water and acetone. We hereby present the capability of LTCC-based systems in fluid identification by detecting their electrical permittivity using capacitance measurement.

A Microfluidic Fluorescence Immunoassay Test Card for Rapid Detection of Heart-type Fatty Acid Binding Protein

Abstract A kind of easily assembly self-driving test card was developed for the rapid detection and quantification of heart-type fatty acid binding protein (H-FABP) utilizing time-resolved fluorescence microspheres as signal probes. It was easy to make microfluidic channel structures with double-sided adhesive and cut out of test card substrate and cover based on polymethyl methacrylate (PMMA) material by the laser cutting technique. The membrane of polystyrene containing maleic anhydride functional groups was coated on PMMA plate surface by dip-coating method. Furthermore, the capture antibody was immobilized effectively on PMMA surface by covalent binding with maleic anhydride groups. The cover was treated with plasma treatment to improve the hydrophilic ability, so that the liquid could flow smoothly in the microchannel. The whole analysis process could be completed within 10 min. There was a very good linear correlation between response and H-FABP concentration in the range of 0.5−100 ng mL−1 (R2 = 0.9966), and the detection limit was 0.1 ng mL−1 (S/N = 3). The intra-assay precision was less than 10% and the inter-assay precision was less than 15%. This detection method has the advantages such as high sensitivity, fast detection and good accuracy.

Microfluidic Formation of Membrane-Free Aqueous Coacervate Droplets in Water.

We report on the formation of coacervate droplets from poly(diallyldimethylammonium chloride) with either adenosine triphosphate or carboxymethyl-dextran using a microfluidic flow-focusing system. The formed droplets exhibit improved stability and narrower size distributions for both coacervate compositions when compared to the conventional vortex dispersion techniques. We also demonstrate the use of two parallel flow-focusing channels for the simultaneous formation and co-location of two distinct populations of coacervate droplets containing different DNA oligonucleotides, and that the populations can coexist in close proximity up to 48 h without detectable exchange of genetic information. Our results show that the observed improvements in droplet stability and size distribution may be scaled with ease. In addition, the ability to encapsulate different materials into coacervate droplets using a microfluidic channel structure allows for their use as cell-mimicking compartments.

Microfluidic Formation of Membrane‐Free Aqueous Coacervate Droplets in Water

AbstractWe report on the formation of coacervate droplets from poly(diallyldimethylammonium chloride) with either adenosine triphosphate or carboxymethyl‐dextran using a microfluidic flow‐focusing system. The formed droplets exhibit improved stability and narrower size distributions for both coacervate compositions when compared to the conventional vortex dispersion techniques. We also demonstrate the use of two parallel flow‐focusing channels for the simultaneous formation and co‐location of two distinct populations of coacervate droplets containing different DNA oligonucleotides, and that the populations can coexist in close proximity up to 48 h without detectable exchange of genetic information. Our results show that the observed improvements in droplet stability and size distribution may be scaled with ease. In addition, the ability to encapsulate different materials into coacervate droplets using a microfluidic channel structure allows for their use as cell‐mimicking compartments.