Glass Microfluidic Chip Research Articles

Laser Aggregometry Assessment of Blood Microrheology in a Slit Fluidic Channel Covered With Endothelial Cells.

The blood rheology in vitro in glass or plastic microfluidic chips is different from that in vivo in blood vessels with similar geometry. Absence of vascular endothelium is suggested to cause these discrepancies. This work aims to perform in vitro measurements of blood microrheologic parameters in a slit microfluidic channel covered with endothelial cells (HUVEC). The laser aggregometry was employed to measure the intensity of laser light, backscattered from the blood flow, as a function of shear stress to evaluate the hydrodynamic strength of red blood cells (RBC) aggregates in terms of critical shear stress (CSS). The results demonstrated a decrease in CSS accompanied by an increase in the accuracy of its measurement at similar shear stresses when endothelial cells were present in the channel. The findings hold valuable implications for advanced approaches for endothelization of microfluidic devices, facilitating the study of blood flow dynamics in physiologically more relevant environment.

Ultraviolet supercontinuum generation using a differentially-pumped integrated glass chip

We investigate the generation of ultrabroadband femtosecond ultraviolet (UV) radiation via third-order harmonic generation in highly confined gas media. A dual-stage differential-pumping scheme integrated into a glass microfluidic chip provides an exceptional gas confinement up to several bar and allows the apparatus to be operated under high-vacuum environment. UV pulses are generated both in argon and neon with up to ∼0.8 μJ energy and 0.2% conversion efficiency for spectra that cover the UVB and UVC regions between 200 and 325 nm. Numerical simulations based on the unidirectional pulse propagation equation reveal that ionization plays a critical role for extending the spectral bandwidth of the generated third-harmonic pulse beyond the tripled 800 nm driving laser pulse bandwidth. By delivering UV supercontinua supporting Fourier transform limits below 2 fs, as well as comparable pulse energies with respect to capillary-based techniques that typically provide high spectral tunability but produce narrower bandwidths, our compact device makes a step forward towards the production and application of sub-fs UV pulses for the investigation of electron dynamics in neutral molecules.

Monolithic 3D nanoelectrospray emitters based on a continuous fluid-assisted etching strategy for glass droplet microfluidic chip-mass spectrometry

A continuous fluid-assisted etching strategy was proposed for fabricating 3D nESI emitters monolithically integrated on glass microfluidic chips. The established glass droplet microfluidic chip-MS system could detect neurochemicals in pL droplets.

Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification.

As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 μM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.

Kinetically Controlled Nucleation Enabled by Tunable Microfluidic Mixing for the Synthesis of Dendritic Au@Pt Core/Shell Nanomaterials.

The nucleation stage plays a decisive role in determining nanocrystal morphology and properties; hence, the ability to regulate nucleation is critical for achieving high-level control. Herein, glass microfluidic chips with S-shaped mixing units are designed for the synthesis of Au@Pt core/shell materials. The use of hydrodynamics to tune the nucleation kinetics is explored by varying the number of mixing units. Dendritic Au@Pt core/shell nanomaterials are controllably synthesized and a formation mechanism is proposed. As-synthesized Au@Pt exhibited excellent ethanol oxidation activity under alkaline conditions (8.4 times that of commercial Pt/C). This approach is also successfully applied to the synthesize of Au@Pd core/shell nanomaterials, thus demonstrating its generality.

A Compact Imaging Platform for Conducting C. elegans Phenotypic Assays on Earth and in Spaceflight.

The model organism Caenorhabditis elegans is used in a variety of applications ranging from fundamental biological studies, to drug screening, to disease modeling, and to space-biology investigations. These applications rely on conducting whole-organism phenotypic assays involving animal behavior and locomotion. In this study, we report a 3D printed compact imaging platform (CIP) that is integrated with a smart-device camera for the whole-organism phenotyping of C. elegans. The CIP has no external optical elements and does not require mechanical focusing, simplifying the optical configuration. The small footprint of the system powered with a standard USB provides capabilities ranging from plug-and-play, to parallel operation, and to housing it in incubators for temperature control. We demonstrate on Earth the compatibility of the CIP with different C. elegans substrates, including agar plates, liquid droplets on glass slides and microfluidic chips. We validate the system with behavioral and thrashing assays and show that the phenotypic readouts are in good agreement with the literature data. We conduct a pilot study with mutants and show that the phenotypic data collected from the CIP distinguishes these mutants. Finally, we discuss how the simplicity and versatility offered by CIP makes it amenable to future C. elegans investigations on the International Space Station, where science experiments are constrained by system size, payload weight and crew time. Overall, the compactness, portability and ease-of-use makes the CIP desirable for research and educational outreach applications on Earth and in space.

Voltage-induced concentration enhancement of analyte solutes in microfluidic chips

Microfluidic-based enrichment techniques have had a profound impact on chemistry, owing to their ability to improve the sensitivity of detection by increasing the concentration of analytes in minute fluid volumes. Herein, concentration enrichment of analyte solutes is achieved by using voltage assist in a microchip with two reservoirs. A numerical model is developed to describe the complex analyte focusing process, which to date has not been investigated before. Numerical computations are systematically conducted to study the influences of applied voltage, mass transfer coefficient, electrode location, reservoir diameter and number of mass transfer channels on the concentration enrichment in a designed Polydimethylsiloxane (PDMS)/Glass microfluidic electrophoresis chip. The electric fields, concentration distributions, and electrophoretic fluxes are obtained, which can reveal insightful enrichment mechanisms. It is found that the factors that can increase the electrophoretic flux in the mass transfer channel and enhance the electric field strength in the enrichment reservoir, such as moving the electrode back or increasing the number of mass transfer channels, are particularly important to improve the enrichment performance. The final microchip after considering the Joule heating effect has a 335-fold and 2.8-fold maximum and average concentration enrichments, respectively. Furthermore, this method is applied to the experimental enrichment of Rhodamine B and heavy metal cadmium (II) ions to test it performance.

Back Cover: A velocity program using the Kanade–Lucas–Tomasi feature‐tracking algorithm with demonstration for pressure and electroosmosis conditions

DOI: 10.1002/elps.202100177 The cover picture shows the microparticles which were tracked using the KLT feature-tracking algorithm under pressure-driven and electroosmosis conditions. The top of the image features the T8050 glass microfluidic chip which the tests were performed on. The insets at the T-intersection of the microfluidic chip demonstrates a series of silica microfluidic particles flowing through the buffer solution of the microfluidic chip. In this study, these microparticles were tracked, and the resulting velocity profiles were computed, to demonstrate the effectiveness of the KLT feature-tracking algorithm.

Microfluidics-Based Low Salinity Wettability Alteration Study of Naphthenic-Acid-Adsorbed Calcite Surfaces

Microfluidics is relatively a new area in the oil and gas industry and has great potential to be used as an effective tool to address various outstanding research questions where microscale investigation is necessary. Low salinity brine flooding has been known to enhance oil recovery in carbonate reservoirs through a wettability alteration mechanism. Wettability alteration is a molecular-scale phenomenon that is often characterized at a mesoscale through contact angle experiments. By using microfluidic chips, the low salinity effects involving solid–fluid interactions could be directly visualized, and the wettability alteration could be verified at microscale. However, to replicate solid–fluid interactions involved in carbonate reservoirs, the internal wetting surfaces must be transformed to carbonate surfaces. In this study, first, wetting surfaces of straight-channel glass microfluidic chips were functionalized using a metal-chelating silane coupling agent, and then, the surfaces were coated with CaCO3 using a layer-by-layer (LbL) deposition process. The calcite-coated straight-channel glass microfluidic chips were then used to investigate the effects of brine salinity and the role of divalent ions in the wettability alteration of oil-wet calcite surfaces at both room temperature and high temperature (70 °C). Naphthenic acid was used as the surface-active component in a model oil to render calcite surfaces oil wet. Six single-electrolyte-based brines were used in this study: high salinity 5 M NaCl, seawater equivalent 0.656 M NaCl, and 4-times diluted seawater-equivalent low salinity brines─0.164 M ionic strength NaCl, Na2SO4, MgSO4, and MgCl2. The low salinity brines were found to induce significant wettability alteration on naphthenic-acid-adsorbed calcite surfaces at ambient temperature. Low salinity Na2SO4 resulted in the highest wettability alteration followed by low salinity NaCl solution. Insignificant wettability alteration was observed in 0.656 M NaCl compared to 0.164 M NaCl where the wettability alteration was significant, suggesting the extent of wettability alteration increases with reduction in brine salinity. Magnesium ions were found to be unfavorable for wettability alteration in the presence or absence of sulfate ions. Exposure to higher temperature resulted in no or insignificant further wettability alteration in most of the brines.

Scaled-up droplet generation in parallelised 3D flow focusing junctions

Monodispersed organic phase droplets with an average diameter from 20 to 200 µm were produced at the rate of up to 20,000 droplets per second in a glass microfluidic chip composed of 7 parallel 3D flow focusing junctions with 100 µm-deep channels. The continuous phase was 2 wt% polyvinyl alcohol solution, while the dispersed phase was dichloromethane, n-dodecane, and polydimethylsiloxane 10 cSt fluid corresponding to the dispersed-to-continuous-phase viscosity ratio of 0.2, 0.8 and 6.1, respectively. Four different droplet generation regimes were observed, dripping, squeezing, jetting, and threading. The regions where each of these regimes was stable were mapped using Weber number of the dispersed phase and capillary number of the continuous phase. The transitions between the droplet formation regimes were governed by the Weber number of the dispersed phase, indicating that inertial forces in the dispersed phase were more relevant than viscous forces in controlling the transition. Stable droplet generation in dripping regime in each junction was maintained for at least 6 h. The coefficient of variation of droplet sizes from individual junctions and all junctions combined was < 3% under optimal conditions. The droplet size variations between different junctions were greater than those within each junction. Liquid plugs were produced in the squeezing regime at the dispersed-to-continuous phase flow rate ratio greater than one. This study is the first investigation of droplet generation in multiple 3D flow-focusing junctions with potential applications for the production of drug microcarriers using emulsification solvent evaporation, especially for the encapsulation and controlled delivery of lipophilic drugs.

Determination of Nanoplastics Using a Novel Contactless Conductivity Detector with Controllable Geometric Parameters.

Plastic waste in the environment is continuously degraded to form nanoplastic particles, and its harm has attracted widespread attention. At present, the identification and quantification of nanoplastics are performed by visual observation and using some spectroscopy methods, which are time-consuming and lack accuracy. Therefore, this study proposes a contactless conductivity detector (C4D) based on a glass microfluidic chip with controllable geometric parameters to quantify nanoplastics. We found that when the insulating layer thickness was 15 μm, the electrode spacing was 1 mm, and the shielding method was on-chip shielding, the detector displayed the best performance. The detector possesses a simple structure with high sensitivity and outstanding reproducibility, that is, the limit of detection of KCl solutions can reach the micromolar level, and the intraday RSD is 0.2% (n = 5). This work uses a microfluidic chip C4D to study nanoplastics for the first time, and the limit of detection is 0.25 μg/mL and the quantitative limit is 0.8 μg/mL. In addition, plant experiments have verified that terrestrial plants can absorb nanoplastics in water, expanding the application of contactless conductivity detectors and providing a new method for the quantitative analysis of nanoplastics.

Microfluidic active pressure and flow stabiliser

In microfluidics, a well-known challenge is to obtain reproducible results, often constrained by unstable pressures or flow rates. Today, there are existing stabilisers made for low-pressure microfluidics or high-pressure macrofluidics, often consisting of passive membranes, which cannot stabilise long-term fluctuations. In this work, a novel stabilisation method that is able to handle high pressures in microfluidics is presented. It is based on upstream flow capacitance and thermal control of the fluid’s viscosity through a PID controlled restrictor-chip. The stabiliser consists of a high-pressure-resistant microfluidic glass chip with integrated thin films, used for resistive heating. Thereby, the stabiliser has no moving parts. The quality of the stabilisation was evaluated with an ISCO pump, an HPLC pump, and a Harvard pump. The stability was greatly improved for all three pumps, with the ISCO reaching the highest relative precision of 0.035% and the best accuracy of 8.0 ppm. Poor accuracy of a pump was compensated for in the control algorithm, as it otherwise reduced the capacity to stabilise longer times. As the dead volume of the stabiliser was only 16 nL, it can be integrated into micro-total-analysis- or other lab-on-a-chip-systems. By this work, a new approach to improve the control of microfluidic systems has been achieved.

Study on the Growth Kinetics and Morphology of Methane Hydrate Film in a Porous Glass Microfluidic Device

Natural gas hydrates are widely considered one of the most promising green resources with large reserves. Most natural gas hydrates exist in deep-sea porous sediments. In order to achieve highly efficient exploration of natural gas hydrates, a fundamental understanding of hydrate growth becomes highly significant. Most hydrate film growth studies have been carried out on the surface of fluid droplets in in an open space, but some experimental visual works have been performed in a confined porous space. In this work, the growth behavior of methane hydrate film on pore interior surfaces was directly visualized and studied by using a transparent high-pressure glass microfluidic chip with a porous structure. The lateral growth kinetics of methane hydrate film was directly measured on the glass pore interior surface. The dimensionless parameter (−∆G/(RT)) presented by the Gibbs free energy change was used for the expression of driving force to explain the dependence of methane hydrate film growth kinetics and morphology on the driving force in confined pores. The thickening growth phenomenon of the methane hydrate film in micropores was also visualized. The results confirm that the film thickening growth process is mainly determined by water molecule diffusion in the methane hydrate film in glass-confined pores. The findings obtained in this work could help to develop a solid understanding on the formation and growth mechanisms of methane hydrate film in a confined porous space.

A simple approach to fabricate multi-layer glass microfluidic chips based on laser processing and thermocompression bonding

A simple approach to fabricate multi-layer glass microfluidic chips based on laser processing and thermocompression bonding

Research on Micro-Analysis System of Dye in Water Sample Based on Magnetic Nano-TiO2

Magnetic Nano-Photocatalytic Material (NMPC) helps separate and recover nano photocatalyst in water treatment. However, it is rarely reported that a photocatalyst can be separated online in photocatalytic microreactors. In this paper, a typical dye methylene blue was photocatalytically degraded in glass microfluidic chip by using Fe3O4@ SiO2@ TiO2 (FST) as the magnetic nanocatalyst, the UV-LED as the ultraviolet light source, and ultraviolet-visible spectrophotometer as the detector. The FST was easily separated by an external magnetic field, thereby realizing rapid online detection of methylene blue. During the preparation of FST, the hydrothermal method was used to treat the obtained FST nanoparticles in 100°C boiling water bath, and the titanium-iron ratio was optimized, so as to obtain FST nano-photocatalyst with high photocatalytic performance and good dispersibility. With 1.0 g/L FST/8%H2O2 being the catalytic oxidation system, the sample flow rate being 300 μL/h, the reaction temperature being 45 °C, the degradation rate of methylene blue has reached 100%. It only took 25 min to complete one measurement. The FST consumed per measurement was only 125 μg. The RSD of the photodegradation rate was 2.5% (n=9).

A microfluidic chip for on-line derivatization and application to in vivo neurochemical monitoring.

Microfluidic chips can perform a broad range of automated fluid manipulation operations for chemical analysis including on-line reactions. Derivatization reactions carried out on-chip reduce manual sample preparation and improve experimental throughput. In this work we develop a chip for on-line benzoyl chloride derivatization coupled to microdialysis, an in vivo sampling technique. Benzoyl chloride derivatization is useful for the analysis of small molecule neurochemicals in complex biological matrices using HPLC-MS/MS. The addition of one or more benzoyl groups to small, polar compounds containing amines, phenols, thiols, and certain alcohols improves reversed phase chromatographic retention, electrospray ionization efficiency, and analyte stability. The current derivatization protocol requires a three-step manual sample preparation, which ultimately limits the utility of this method for rapid sample collection and large sample sets. A glass microfluidic chip was developed for derivatizing microdialysis fractions on-line as they exit the probe for collection and off-line analysis with HPLC-MS/MS. Calibration curves for 21 neurochemicals prepared using the on-chip method showed linearity (R2 > 0.99), limits of detection (0.1-500 nM), and peak area RSDs (4-14%) comparable to manual derivatization. Method temporal resolution was investigated both in vitro and in vivo showing rapid rise times for all analytes, which was limited by fraction length (3 min) rather than the device. The platform was applied to basal measurements in the striatum of awake rats where 19 of 21 neurochemicals were above the limit of detection. For a typical 2 h study, a minimum of 120 pipetting steps are eliminated per animal. Such a device provides a useful tool for the analysis of small molecules in biological matrices which may extend beyond microdialysis to other sampling techniques.

On-Line Coupling of Chip-Electrochromatography and Ion Mobility Spectrometry.

We report the first hyphenation of chip-electrochromatography (ChEC) with ion mobility spectrometry (IMS). This approach combines the separation power of two electrokinetically driven separation techniques, the first in liquid phase and the second in gas phase, with a label-free detection of the analytes. For achieving this, a microfluidic glass chip incorporating a monolithic separation column, a nanofluidic liquid junction for providing post-column electrical contact, and a monolithically integrated electrospray emitter was developed. This device was successfully coupled to a custom-built high-resolution drift tube IMS with shifted potentials. After proof-of-concept studies in which a mixture of five model compounds was analyzed in less than 80 s, this first ChEC-IMS system was applied to a more complex sample, the analysis of herbicides spiked in the wine matrix. The use of ChEC before IMS detection not only facilitated the peak allocation and increased the peak capacity but also enabled analyte quantification. As both, ChEC and IMS work at ambient conditions and are driven by high voltages, no bulky pumping systems are needed, neither for the hydrodynamic pumping of the mobile phase as in high-performance liquid chromatography nor for generating a vacuum system as in mass spectrometry. Accordingly, the approach has great potential as a portable analytical system for field analysis of complex mixtures.

Membrane-integrated glass chip for two-directional observation of epithelial cells

The investigation of the basic properties of epithelial cells, such as the observation of the morphology and evaluation of the barrier function, is important for pharmacotherapeutic applications. These investigations are traditionally achieved by culturing epithelial cells on Transwell filters. However, the cross section of the cell layer cannot be directly observed with this method, and the permeability measurement requires many steps. Herein, we developed a glass microfluidic chip sandwiching a porous PET membrane between two glass capillaries and present a model with two advantages over conventional models: 1) direct top-view and cross-sectional observation of the cell layer and 2) facile assessment of the epithelial permeability without laborious manual sampling. We designed and fabricated a glass microfluidic chip and evaluated its characteristics. We then cultured the epithelial cells in the chip to demonstrate the observation of the cell layer in both the x–y and x–z planes under a microscope. Furthermore, we measured the permeation of the fluorescence probe through a human trophoblast cell layer cultured on the chip without manual sampling. We believe that our chip would be a powerful tool for analysis of the epithelial cells with high usability.

In Situ Microfluidic Preparation and Solidification of Alginate Microgels

Biomimetic fabrication of alginate beads has promising applications in the field of synthetic bioarchitecture. Combining microfluidic technology with in situ gelation enables the creation of alginate microgels with precisely tunable size, as well as allowing control of the crosslinking process. Owing to the wide range of applications of alginate microgel beads, this study aimed to develop various microfluidic models for the generation of such beads by investigating the influence of several parameters on their morphologies and dispersity. Four types of glass microfluidic chips with flow focusing or co-flowing droplet generators were used to continuously form alginate droplets, with the possibility of either internal or external alginate gelation by a cross-linking agent supplied by a microfluidic channel. In all four models, alginate was used at a fixed concentration, Span 80 was used as a surfactant to improve the long-term stability of the beads, either mineral oil or oleic acid was used as a continuous phase, and either calcium carbonate (CaCO3) or calcium chloride (CaCl2) was used as a crosslinking agent. The generated beads exhibited various architectures, including individual monodisperse or polydisperse beads, small clusters, and multicompartment systems. The results of the study revealed the importance of microfluidic design and gelation strategy for the generation of stable polymeric architectures. The current study proposes a simple user’s guide to create alginate microgels in various architectures. The fabricated biomimetic models in the form of polymeric-based vesicles can be further exploited in several applications, including cell-like structures, tissue engineering, and cell and drug encapsulation. Additional investigations will be needed, however, to improve these models so that they more closely resemble the natural structures of cells and tissues.

Attomolar Sensing Based on Liquid Interface-Assisted Surface-Enhanced Raman Scattering in Microfluidic Chip by Femtosecond Laser Processing.

Surface-enhanced Raman scattering (SERS) is a multidisciplinary trace analysis technique based on plasmonic effects. The development of SERS microfluidic chips has been exploited extensively in recent times impacting on applications in diverse fields. However, despite much progress, the excitation of label-free molecules is extremely challenging when analyte concentrations are lower than 1 nM because of the blinking SERS effect. In this paper, a novel analytical strategy which can achieve detection limits at an attomolar level is proposed. This performance improvement is due to the use of a glass microfluidic chip that features an analyte air-solution interface which forms on the SERS substrate in the microfluidic channel, whereby the analyte molecules aggregate locally at the interface during the measurement, hence the term liquid interface-assisted SERS (LI-SERS). The microfluidic chips are fabricated using hybrid femtosecond (fs) laser processing consisting of fs laser-assisted chemical etching, selective metallization, and metal surface nanostructuring. The novel LI-SERS technique can achieve an analytical enhancement factor of 1.5 × 1014, providing a detection limit below 10-17 M (<10 aM). The mechanism for the extraordinary enhancement afforded by LI-SERS is attributed to Marangoni convection induced by the photothermal effect.