Microfluidic Substrate Research Articles

Capillary filling dynamics in closed-end carbon nanotubes—Defying the classical Lucas–Washburn paradigm

The emergence of two-dimensional (2D) materials such as carbon nanotubes (CNTs) offers the possibility of exploring new regimes of capillarity and wetting that remained inaccessible with traditional microfluidic and nanofluidic substrates. Here, we bring out the non-intuitive capillary filling regimes in closed-end CNTs using molecular-level investigations. Contrary to the existing understanding of the advancing liquid meniscus getting retarded by the viscous resistance offered by an entrapped vapor phase in a three-dimensional capillary, here the liquid meniscus is shown to accelerate toward the later stages of the dynamic wetting, which is attributed to the modified surface friction due to a 2D interface. This apparently counterintuitive observation is qualitatively linked to the local pressure fluctuations across the meniscus caused by the spontaneous bombardment of the entrapped vapor molecules, which may ramify into hitherto unexplored phenomena of a shape-reversed meniscus advancing in the 2-D pore. We further develop a simple analytical model to represent the essential physics of the resulting capillary filling dynamics, featuring significant deviations from the classical Lucas–Washburn paradigm. These results may turn out to be imperative in realizing new regimes of capillarity in 2D materials in multifarious applications, ranging from energy storage and water filtration to thin film flows in integrated electronics and photonic devices.

Longitudinal torsional ultrasonic vibratory assistant milling of borosilicate glass material removal mechanism based on the thickness of undeformed chips

Borosilicate glass is an ideal material for microfluidic chip substrates due to its excellent light transmittance and stable chemical properties. However, it is also prone to brittle fracture during processing, making it a typical difficult-to-machine material. As an emerging processing technology, longitudinal torsional ultrasonic assistant milling (LTUVAM) can effectively reduce the surface damage of glass materials and improve the proportion of plastic removal of materials. The mechanism of LTUVAM of borosilicate glass was studied in this paper. Critical undeformed chip thickness (hc) is a key factor in achieving plastic material removal. At present, the influence of LTUVAM on the hc is not clear. Therefore, in this paper, the material-specific cutting energy model in the LTUVAM process was established to predict the hc. Firstly, the motion path of LTUVAM was analyzed, and the undeformed chip thickness model and the tool-workpiece separation rate model were established. Then, based on the above model, the material-specific cutting energy model was established according to the material removal principle. Finally, an LTUVAM orthogonal experiment was carried out to study the surface quality of the material. The experimental results showed that with the increase of ultrasonic power, the roughness and side damage area increased first and then decreased. With the increase of spindle speed, it showed that the roughness and side damage area decreased first and then increased. With the increase of feed per tooth, it showed that the roughness increased first and then decreased, and then increased, and the side damage area increased first and then decreased. Through the analysis of the experimental and model results, the increase of the separation rate between the tool and the workpiece contributes to the increase of the hc and the improvement of the processing quality.

Bioprinted Multi-Composition Array Mimicking Tumor Microenvironments to Evaluate Drug Efficacy with Multivariable Analysis.

Current organ-on-a-chip technologies confront limitations in effectively recapitulating the intricate in vivo microenvironments and accommodating diverse experimental conditions on a single device. Here, a novel approach for constructing a multi-composition tumor array on a single microfluidic device, mimicking complex transport phenomena within tumor microenvironments (TMEs) and allowing for simultaneous evaluation of drug efficacy across 12 distinct conditions is presented. The TME array formed by bioprinting on a microfluidic substrate consists of 36 individual TME models, each characterized by one of three different compositions and tested under four varying drug concentrations. Notably, the TME model exhibits precise compartmentalization, fostering the development of self-organized vascular endothelial barriers surrounding breast cancer spheroids affecting substance transport. Multivariable screening and analysis of diverse conditions, including model complexity, replicates, and drug concentrations, within a single microfluidic platform, highlight the synergistic potential of integrating bioprinting with microfluidics to evaluate drug responses across diverse TME conditions comprehensively.

Spatial and temporal detection of root exudates with a paper-based microfluidic device

Root exudates control critical processes in the rhizosphere, retaining water, selecting for beneficial microorganisms or solubilising nutrients prior to uptake by the plant. Analysing root exudation patterns however is challenging because existing methods are often destructive and unable to resolve spatial and temporal variations in the production of root exudates. Here, we present a paper-based microfluidic device with integrated colorimetric sensors for the continuous extraction and analysis of root exudates along plant roots. The microfluidic device used standard filter paper wax printer to create channels for water to carry the exudates towards the sensors. TiO2 nanotubes/alginate hydrogel-based sensors were used to analyse the glucose content of the root exudates of living plants. The study shows that the paper microfluidic substrate successfully extracts the released glucose from the root, and transfers it to the hydrogel-based sensor to be colorimetrically detected from independent sections of the root at different times, up to 7 days. This method was tested on two different wheat varieties Triticum aestivum (rgt Tocayo and Filon varieties), where significant differences in exudation patterns were recorded. This research demonstrates the feasibility of low-cost technological solution for high precision screening and diagnostic of the biochemical composition of root exudates.

Cell Patterning Using Magnetic-Archimedes Strategy.

Cell patterning, allowing precise control of cell positioning, presents a unique advantage in the study of cell behavior. In this protocol, a cell patterning strategy based on the Magnetic-Archimedes (Mag-Arch) effect is introduced. This approach enables precise control of cell distribution without the use of ink materials or labeling particles. By introducing a paramagnetic reagent to enhance the magnetic susceptibility of the cell culture medium, cells are repelled by magnets and arrange themselves into a pattern complementary to the magnet sets positioned beneath the microfluidic substrate. In this article, detailed procedures for cell patterning using the Mag-Arch-based strategy are provided. Methods for patterning single-cell types as well as multiple cell types for co-culture experiments are offered. Additionally, comprehensive instructions for fabricating microfluidic devices containing channels for cell patterning are provided. Achieving this feature using parallel methods is challenging but can be done in a simplified and cost-effective manner. Employing Mag-Arch-based cell patterning equips researchers with a powerful tool for in vitro research.

Natural Indigenous Paper Substrates for Colorimetric Bioassays in Portable Analytical Systems: Sustainable Solutions from the Rain Forests to the Great Plains.

Point-of-care (POC) devices can provide inexpensive, practical, and expedited solutions for applications ranging from biomedicine to environmental monitoring. This work reports on the development of low-cost microfluidic substrates for POC systems suitable for analytical assays, while also satisfying the need for social and environmentally conscious practices regarding circular economy, waste reduction, and the use of local resources. Thus, an innovative greener process to extract cellulose from plants including abaca, cotton, kozo, linen, and sisal, originating from different places around the world, is developed, and then the corresponding paper substrates are obtained to serve as platforms for POC assays. Hydrophobic wax is used to delineate channels that are able to guide solutions into chambers where the colorimetric assay for total cholesterol quantification is carried out as a proof of concept. Morphological and physicochemical analyses are performed, including the evaluation of fiber diameter, shape and density, and mechanical and thermal properties, together with peel adhesion of the printed wax channels. Contact angle and capillary flow tests ascertain the suitability of the substrates for liquid assays and overall viability as low-cost, sustainable microfluidic substrates for POC applications.

Direct deep UV lithography to micropattern PMMA for stem cell culture.

Microengineering is increasingly being used for controlling the microenvironment of stem cells. Here, a novel method for fabricating structures with subcellular dimensions in commonly available thermoplastic poly(methyl methacrylate) (PMMA) is shown. Microstructures are produced in PMMA substrates using Deep Ultraviolet lithography, and the effect of different developers is described. Microgrooves fabricated in PMMA are used for the neuronal differentiation of mouse embryonic stem cells (mESCs) directly on the polymer. The fabrication of 3D, curvilinear patterned surfaces is also highlighted. A 3D multilayered microfluidic chip is fabricated using this method, which includes a porous polycarbonate (PC) membrane as cell culture substrate. Besides directly manufacturing PMMA-based microfluidic devices, an application of the novel approach is shown where a reusable PMMA master is created for replicating microstructures with polydimethylsiloxane (PDMS). As an application example, microchannels fabricated in PDMS are used to selectively expose mESCs to soluble factors in a localized manner. The described microfabrication process offers a remarkably simple method to fabricate for example multifunctional topographical or microfluidic culture substrates outside cleanrooms, thereby using inexpensive and widely accessible equipment. The versatility of the underlying process could find various applications also in optical systems and surface modification of biomedical implants.

Stretchable Enzymatic Biofuel Cells Based on Microfluidic Structured Elastomeric Polydimethylsiloxane with Wrinkled Gold Electrodes

AbstractVarious sensors and electronic devices are recently developed to monitor human health in mechanically flexible or even stretchable forms for intimate contact with non‐flat curvilinear surfaces of the human body. For successful operation of these devices, finding a proper way to electrically power them is very important. In this work, glucose/oxygen fueled enzymatic biofuel cells (EBFCs) based on microfluidic structured elastomeric polydimethylsiloxane substrate with wrinkled gold (Au) electrodes are suggested for power supply. For doing that, firstly, bottom surface of microfluidic channel is covered with buckled Au electrodes for stretchability. By microfluidic design showing capillary imbibition through fluidic channels, loading of catalyts is promoted. Interestingly, buckled Au electrodes induce much better anodic and cathodic reaction rates than those of non‐buckled Au electrodes by 25% and 33%, respectively. This is because surface area and the amount of catalyst loading in electrodes increase by Au wrinkling. In evaluations of EBFCs using the buckled Au electrodes, maximum power density reaches 7.1 ± 0.64 µW cm−2, while they show decent performance of 5.4 ± 0.49 µW cm−2 even under external stretching. Taken together, it is corroborated that such proposed stretchable EBFCs are alternative for providing electrical power in wearable or implantable devices.

Novel molecularly imprinted nanogel modified microfluidic paper-based SERS substrate for simultaneous detection of bisphenol A and bisphenol S traces in plastics

Paper-based surface-enhanced Raman scattering (SERS) optical nanoprobes provide ultrasensitive analyte detection; however, they lack selectivity, making them difficult to use in real-world sample analysis without a pretreatment process. This work describes the design of a microfluidic paper-based SERS substrate based on molecularly imprinted nanogels decorated with silver nanoparticles to simultaneously detect bisphenol A (BPA) and bisphenol S (BPS) traces in plastic toys and receipts. The synthesized nanogels have two characteristics that boost SERS performance: molecularly imprinted cavities that allow for selective adsorption and a wrinkled surface that creates uniformly distributed hot spots. Simple paper-based sensor devices were built as ‘drop and read’ SERS substrates with a separate reservoir to detect a single target, while advanced SERS platforms were designed as a microfluidic chip with two reservoirs connected by a channel for simultaneous detection of BPA and BPS. The SERS platform with a single reservoir showed outstanding analytical performance for the detection of BPA and BPS, with low detection limits of 0.38 pM and 0.37 pM, respectively. The microfluidic paper-based sensor allowed simultaneous and selective detection of BPA and BPS with detection limits estimated at 0.68 nM and 0.47 nM, respectively. The developed sensors are successfully applied to detect BPA and BPS in plastic products and receipts. Finally, the results obtained with our method showed greater sensitivity than those of commercially available ELISA kits, and the acquired values within the ELISA detection range were in excellent agreement.

3D bio-printed hydrogel inks promoting lung cancer cell growth in a lab-on-chip culturing platform

The results of a lab-on-chip (LOC) platform fabrication equipped with a hydrogel matrix is reported. A 3D printing technique was used to provide a hybrid, “sandwiched” type structure, including two microfluidic substrates of different origins. Special attention was paid to achieving uniformly bio-printed microfluidic hydrogel layers of a unique composition. Six different hydrogel inks were proposed containing sodium alginate, agar, chitosan, gelatin, methylcellulose, deionized water, or 0.9% NaCl, varying in proportions. All of them exhibited appropriate mechanical properties showing, e.g., the value of elasticity modulus as similar to that of biological tissues, such as skin. Utilizing our biocompatible, entirely 3D bio-printed structure, for the first time, a multi-drug-resistant lung cancer cell line (H69AR) was cultured on-chip. Biological validation of the device was performed qualitatively and quantitatively utilizing LIVE/DEAD assays and Presto blue staining. Although all bio-inks exhibited acceptable cell viability, the best results were obtained for the hydrogel composition including 3% sodium alginate + 7% gelatin + 90% NaCl (0.9%), reaching approximately 127.2% after 24 h and 105.4% after 48 h compared to the control group (100%). Further research in this area will focus on the microfluidic culture of the chosen cancer cell line (H69AR) and the development of novel drug delivery strategies towards appropriate in vivo models for chemotherapy and polychemotherapy treatment.Graphical abstract

Flexible, label free and low-cost paper based microfluidic SERS substrates for thiram detection

Flexible, label free and low-cost paper based microfluidic SERS substrates for thiram detection

Femtosecond Laser Fabrication of Microchannels in Transparent Hard Materials

AbstractThe excellent characteristics of transparent hard materials such as high hardness, high transparency, corrosion resistance, and high temperature resistance enable their applications in microfluidic substrates even in harsh environments. Microchannels are important parts in microfluidic systems, and the preparation of microchannel structures in transparent hard materials deserves further in‐depth study. The traditional processing method is contact processing with large thermal influence and low processing efficiency, so it is impossible to obtain complex microchannels with high quality and high aspect ratio. The femtosecond laser processing is a non‐contact processing approach with no thermal damage, high processing accuracy, and easy to form complex microchannels, making it the best choice for processing microchannels in transparent hard materials. This work reviews the recent advances in femtosecond laser processing of transparent hard materials to form microchannel structures, focusing on the reaction mechanism, processing methods, and the obtained microchannel structures, including surface microchannels, 2D microchannels, and 3D microchannels. Furthermore, the application of microchannel structure in microfluidic field, including optical inspection and biochemical reaction, is also described.

Microfluidic jet impact: Spreading, splashing, soft substrate deformation and injection

HypothesisNeedle-free injections using microfluidic jets could be optimized by reducing splashing and controlling injection depth. However, this is impeded by an incomplete understanding on how jet characteristics influence impact outcome. We hypothesise that exploring the relation between microfluidic jet characteristics and substrate shear modulus on impact behavior will assist in predicting and giving insights on the impact outcome on skin and injection endpoints. ExperimentsTo do so, a setup using microfluidic chips, at varying laser powers and stand-off distances, was used to create thermocavitation generated microfluidic jets with ranging characteristics (velocity: 7–77 m/s, diameter: 35–120 μm, Weber-number: 40–4000), which were impacted on substrates with different shear modulus. FindingsSeven impact regimes were found, depending on jet Weber-number and substrate shear modulus, and we identified three thresholds: i) spreading/splashing threshold, ii) dimple formation threshold, and iii) plastic/elastic deformation threshold. The regimes show similarity to skin impact, although the opacity of skin complicated determining the threshold values. Additionally, we found that jet velocity has a higher predictive value for injection depth compared to the Weber-number, and consequently, the jet-diameter. Our findings provide fundamental knowledge on the interaction between microfluidic jets and substrates, and are relevant for optimizing needle-free injections.

Microfluidic paper-based colorimetric quantification of malondialdehyde using silver nanoprism toward on-site biomedical analysis: a new platform for the chemical sensing and biosensing of oxidative stress.

Malondialdehyde (MDA) is a critical product of polyunsaturated adipose acid peroxidation and represents a common biomarker of oxidative stress. The effect of different MDA concentrations on human biofluids reflects pathological changes, which has been seen in diverse types of sickness, such as leukemia, diabetes, cancer, cardiovascular disease, and age-related macular degeneration and liver disease. In this study, different types of silver nanoparticles, including silver nanoprism (AgNPrs), silver nanowires (AgNWs), and silver nanospheres (AgNSs), were synthesized and used for the chemosensing of MDA by colorimetric and spectrophotometric methods. Colorimetric tests were performed to identify malondialdehyde in the solution as well as the one-droplet-based microfluidic paper substrate as a miniaturization device for the monitoring of analytes in human real samples. The analytical quantification of the MDA was done using the UV-Vis method. Also, the utilization of the designed chemosensor for the analysis of MDA in real sample was evaluated in human urine samples. Using the spectrophotometric method, MDA was deformed in the linear range of 0.01192 to 1.192 mM with a low limit of quantification of 0.12 μM. Essential significant features of this study include the first application of AgNPrs with high stability and great optical properties without any reagent as an optical sensing probe of MDA and optimized OD-μPCD toward on-site and on-demand MDA screening in real samples diagnosis and the innovative time/color semi-analytical recognition strategy. Moreover, the prepared OD-μPCD decorated by AgNPrs could be a prized candidate for commercialization due to the benefits of the low-cost materials used, like paper and paraffin, and portability. This innovative process led to uniform hydrophilic micro-channels on the surface of cellulose, without the use of a UV lamp, clean room, and organic solvents. This report could be a pioneering work, inspiring simple and effective on-site semi-analytical recognition devices for harmful substances or illegal drugs, which simply consist of a piece of lightweight paper and one drop of the required reagent.

Fabrication of a self-assembled and vascularized tumor array via bioprinting on a microfluidic chip.

A tumor microenvironment (TME) is a complex system that comprises various components, including blood vessels that play a crucial role in supplying nutrients, oxygen, and growth factors, as well as delivering chemotherapy drugs to the tumor mass through the vascular endothelial barrier. To replicate the TME in vitro, several bioprinting and microfluidic organ-on-a-chip technologies have been developed. However, these technologies have not been fully exploited in terms of potential benefits of bioprinting and microfluidics, such as precise spatial control for biological samples, construction of multiple TMEs per microfluidic device, and the ability to adjust culture environments for better biological similarity. In addition, the complex transport phenomena within the vascular endothelial barrier and the aggregated tumor mass in the TME model should be considered before applying the model to drug treatment and screening. In this study, we describe a novel integrative technology that addresses these issues by introducing a self-organized TME array bioprinted on a microfluidic chip consisting of a vascular endothelial barrier surrounding breast cancer spheroids. To integrate the TME array onto the microfluidic platform, a microfluidic substrate for extrusion bioprinting was developed for a cell culture platform, which enables diffusivity control by microstructures and establishes a perfusion culture environment inside the culture channel. We also analyzed the cellular behaviors within the TME array to investigate the influence of the diffusivity on the self-organization process required to form the vascular endothelial barrier surrounding breast cancer spheroids.

The Fabrication and Bonding of Thermoplastic Microfluidics: A Review.

Various fields within biomedical engineering have been afforded rapid scientific advancement through the incorporation of microfluidics. As literature surrounding biological systems become more comprehensive and many microfluidic platforms show potential for commercialization, the development of representative fluidic systems has become more intricate. This has brought increased scrutiny of the material properties of microfluidic substrates. Thermoplastics have been highlighted as a promising material, given their material adaptability and commercial compatibility. This review provides a comprehensive discussion surrounding recent developments pertaining to thermoplastic microfluidic device fabrication. Existing and emerging approaches related to both microchannel fabrication and device assembly are highlighted, with consideration toward how specific approaches induce physical and/or chemical properties that are optimally suited for relevant real-world applications.

Fabrication of high-performance microfluidic SERS substrates by metal-assisted chemical etching of silicon scratches

Surface-enhanced Raman spectroscopy (SERS) substrate-based microfluidic systems are applied extensively in diverse fields. For affordable detection and diagnosis, we propose a novel strategy for flexible, low-cost, and rapid fabrication of microfluidic SERS substrates by metal-assisted chemical etching of scratches on a silicon surface. A silicon substrate was spin-coated with polyketone resin (PK), and patterned by scratching with a diamond tip. Notably, defects created by diamond tip scratching on silicon substrate promoted subsequent metal deposition. A micro/nano nested structure was prepared by metal-assisted chemical etching process based on combined effect of scratching and metal catalysis. The PK layer served as a stable mask during metal deposition and etching. The prepared SERS-active detection sites with micro/nano nested structures exhibited substantial enhancement effects and good stability. Taking rhodamine 6G as a probe molecule, the microfluidic SERS substrate exhibited a high detection capability, with nanomolar detection limits (10−9 M) and high long-term stability (at least 120 days). The micro/nano nested structure exhibited an enhancement factor of 2.725 × 105 compared to a gold film deposited on a flat silicon surface. The proposed method is promising for chemical and biological detection applications.

An active microfluidic sensor based on slow-wave substrate integrated waveguide for measuring complex permittivity of liquids

In this paper, a microfluidic sensor based on slow-wave substrate integrated waveguide (SW-SIW) is proposed to measure the complex permittivity of liquids and it achieves an ultrahigh quality factor of 51156, which is much higher than previous reported designs. The proposed sensor consists of three-layer dielectric substrates and an active circuit. The traditional SIW has the fundamental mode of TE101, whose electric field is concentrated inside the SIW structure. The SW-SIW, which is evolved from traditional SIW structure, has the characteristic of relatively small electrical size due to large equivalent capacitance and the capability to confine the electrical field density further. The internal rows of blind via holes are connecting the top layer of second substrate to the bottom layer of third substrate. In order to further reduce the electrical size, an air cavity is formed in second substrate around blind via holes as it can increase the equivalent capacitance of SW-SIW resonator. The air cavity has an important impact on the resonant frequency of the sensor, and the electrical size could be reduced by enlarging the air cavity. In this paper, an appropriate air cavity is adopted with comprehensive consideration of detection sensitivity and electrical size. The polydimethylsiloxane (PDMS) microfluidic substrate is embedded in first substrate. When the resonator is excited, the electric field is confined above the surface of blind vias. The electric field varies with the volume fraction of aqueous solution injected into the microfluidic channel, and the resonant frequency and quality factor alter correspondingly. The variations in the resonant frequency and quality factor are applied to retrieve the complex permittivity of liquid samples. The proposed sensor is fabricated and tested, it has a dimension of 0.678λ0 × 0.432λ0 (λ0 is the wavelength in free space at 3.7 GHz), and the peak sensitivity and unloaded quality factor are about 2.5 % and 51156, which are improved by 67 % and 5015 % than traditional SIW sensor, respectively. In particular, the sensitivity of measuring loss tangent of liquid sample is improved by several times to hundreds of times with the loss tangent range from 0.1 to 0.9 than other reported sensors. The measured data has a good agreement with the reference complex permittivity.

Biodegradable polymer-based microfluidic membranes for sustainable point-of-care devices

Microfluidic paper-based analytical devices (µPADs) have gained substantial attention as portable analytical devices in various (bio)technological fields, for being affordable, user-friendly, portable, energy efficient and for allowing multiplexed analysis. Although significant progress has been achieved, there is still need for improvement in terms of performance and sustainability. In this work, a biodegradable aliphatic polyester poly(D,L-lactide-co-glycolide acid) lactide:glycolide 50:50 (PDLG), is used to produce pore- and fibre-based membranes, as alternative to conventional paper substrates. Two fabrication methods are used, with potential for industrial scale-up. The processed hydrophobic membranes are post-treated with oxygen plasma to turn them hydrophilic, allowing capillary flows. The physicochemical characterization demonstrates the suitability of the plasma-treated PDLG membranes as microfluidic substrates based on their tailorable morphologies and capillary flow rate from 36.2 ± 4.2 to 84.1 ± 5.2 mm·min−1, excellent mechanical properties and biocompatibility. Further, the membranes maintain their properties for at least 6 months when kept in vacuum and degrade quickly after their use (reaching values higher than 90% after 6 weeks when wet). Finally, portable analytical platforms suitable for the colorimetric quantification of glucose are demonstrated. These results are of great importance for the design and manufacture of a new generation of sustainable portable analytical devices, compatible with circular economy paradigms, and a step forward to cross the challenging academia to industry barrier for their commercialization and widespread adoption.

Natural based reusable materials for microfluidic substrates: The silk road towards sustainable portable analytical systems

Portable analytical systems are versatile tools for application in areas including biomedicine, biosecurity, food safety and environmental monitoring. This work contributes to the increasing demand for low-cost, environmentally friendly substrates for portable analytical systems by using natural Bombyx mori cocoons. Further, silk fibroin is also extracted from these cocoons and electrospun into oriented and randomly oriented fiber substrates. Oxygen plasma treatment is applied to improve their hydrophilicity. Fiber morphology, mechanical properties, porosity, thermal characteristics and surface contact angle are extensively characterized and the ability of the samples for passive capillary flows demonstrated. Plasma treated pressed cocoons show superhydrophilicity, capillary flow rates of 44.8 ± 3.75 mm.min-1, and high mechanical resistance with Young's modulus values up to 592.13 ± 19.83 MPa.The developed materials are used as substrates for the colorimetric quantification of three commonly scrutinized clinical analytes. Hydrophobic barriers are first wax-printed on all samples with a proper design and albumin assays are performed on all substrates. Further assays for uric acid and glucose quantification are successfully accomplished on the pressed cocoons after a simple in between washing step, with overall high coefficient of determination, proving the suitability of the developed materials as low-cost, sustainable and reusable microfluidic substrates.