Microfluidic Formation Research Articles

Eliminating air bubble in microfluidic systems utilizing integrated in-line sloped microstructures.

In most microfluidic systems, formation and accumulation of air and other gas bubbles can be detrimental to their operation. Air bubbles in a microfluidic channel induce a pressure profile fluctuation and therefore disturb the stability of the system. Once an air bubble is generated, itis also extremely difficult to remove such bubbles from the microfluidic systems. In tissue and cell culture microfluidic systems, a single air bubble can completely shear off cells that are being cultured. Air bubbles can be especially problematic in microfluidic systems that have to operate for long periods of time, since completely eliminating the generation of air bubbles for prolonged periods of time, where a single air bubble can ruin an entire multi-day/multi-week experiment, is extremely challenging. Several in-line and off-chip bubble traps have been developed so far, but cannot completely eliminate air bubbles from the system or are relatively difficult to integrate into microfluidic systems. Recent advancements in two-photon polymerization (2PP)-based microfabrication method eliminates the restriction in Z-axis control in conventional two-dimensional microfabricationmethods, and thus enables complex 3D structures to be fabricated at sub-micrometer resolution. In this work, by utilizing this 2PP technique, we developed a sloped microfluidic structure that is capable of both trapping and real-time removal of air bubbles from the system in a consistent and reliable manner. The novel structures and designs developed in this work present a unique opportunity to overcome many limitations of currentmethods, bringstate-of-the-art solutions in air bubble removal, and enable a multifunctional microfluidic device to operate seamlessly free from air bubble disruption. The microfabricated system was tested in both droplet microfluidics and continuous-flow microfluidics applications, and demonstrated to be effective in preventing air bubble aggregation over time. This simple sloped microstructure can be easily integrated into broad ranges ofmicrofluidic devices to minimize bubble introduction, which will contribute to creating a stable and bubble-free microfluidic platform amenable for long-term operation.

Rapid Microfluidic Formation of Uniform Patient-Derived Breast Tumor Spheroids.

Breast cancer is a highly complex, heterogeneous, and multifactorial disease that poses challenges for rapid and efficient treatment and development of personalized therapy. Here, we describe a rapid and reliable method to generate three-dimensional (3D) tumor spheroids in vitro that recapitulate an individual patient's tumor for testing treatments. By employing droplet microfluidics and scaffold materials, tumor cells were encapsulated into a large number of Matrigel-in-oil droplets with precise control over cell numbers and components per droplet. After removal of the oil, large numbers of uniform tumor spheroids were formed within a few hours via Matrigel-supported cell self-assembly. Our microfluidic technique produces uniform-sized tumor spheroids in less than 1 day. This method was used to reproducibly and rapidly generate uniform-sized tumor spheroids derived from patients' breast tumor tissues. As a proof-of-concept application, this method was used to quickly evaluate cancer treatments. We demonstrated that our microfluidic patient-derived tumor cultures not only preserve the genetic characteristics of the original tumor tissue but also provide heterogeneous responses to targeted therapies within 2 days. We believe this method will enable a timely and reliable 3D in vitro culture model, which may be applicable to personalized treatment prediction, drug discovery, and toxicity testing.

Microfluidic Formation of Honeycomb-Patterned Droplets Bounded by Interface Bilayers via Bimodal Molecular Adsorption.

Assembled water-in-oil droplets bounded by lipid bilayers are used in synthetic biology as minimal models of cell tissue. Microfluidic devices successfully generate monodispersed droplets and assemble them via droplet interface bilayesr (DIB) formation. However, a honeycomb pattern of DIB-bounded droplets, similar to epithelial tissues, remains unrealized because the rapid DIB formation between the droplets hinders their ability to form the honeycomb pattern. In this paper, we demonstrate the microfluidic formation of a honeycomb pattern of DIB-bounded droplets using two surfactants with different adsorption rates on the droplet surface. A non-DIB forming surfactant (sorbitan monooleate, Span 80) was mixed with a lipid (1,2-dioleoyl-sn-glycero-3-phosphocholine, PC), whose adsorption rate on the droplet surface and saturated interfacial tension were lower than those of Span 80. By changing the surfactant composition, we established the conditions under which the droplets initially form a honeycomb pattern and subsequently adhere to each other via DIB formation to minimize the interfacial energy. In addition, the reconstituted membrane protein nanopores at the DIBs were able to transport molecules. This new method, using the difference in the adsorption rates of two surfactants, allows the formation of a honeycomb pattern of DIB-bounded droplets in a single step, and thus facilitates research using DIB-bounded droplet assemblies.

Impaired iloprost-induced platelet inhibition and phosphoproteome changes in patients with confirmed pseudohypoparathyroidism type Ia, linked to genetic mutations in GNAS

Patients diagnosed with pseudohypoparathyroidism type Ia (PHP Ia) suffer from hormonal resistance and abnormal postural features, in a condition classified as Albright hereditary osteodystrophy (AHO) syndrome. This syndrome is linked to a maternally inherited mutation in the GNAS complex locus, encoding for the GTPase subunit Gsα. Here, we investigated how platelet phenotype and omics analysis can assist in the often difficult diagnosis. By coupling to the IP receptor, Gsα induces platelet inhibition via adenylyl cyclase and cAMP-dependent protein kinase A (PKA). In platelets from seven patients with suspected AHO, one of the largest cohorts examined, we studied the PKA-induced phenotypic changes. Five patients with a confirmed GNAS mutation, displayed impairments in Gsα-dependent VASP phosphorylation, aggregation, and microfluidic thrombus formation. Analysis of the platelet phosphoproteome revealed 2,516 phosphorylation sites, of which 453 were regulated by Gsα-PKA. Common changes in the patients were: (1) a joint panel of upregulated and downregulated phosphopeptides; (2) overall PKA dependency of the upregulated phosphopeptides; (3) links to key platelet function pathways. In one patient with GNAS mutation, diagnosed as non-AHO, the changes in platelet phosphoproteome were reversed. This combined approach thus revealed multiple phenotypic and molecular biomarkers to assist in the diagnosis of suspected PHP Ia.

Microfluidic droplet formation in co-flow devices fabricated by micro 3D printing

Droplet microfluidics offer many advantages for microscale droplet generation and have great application potential in food emulsion processing. To employ novel technique to develop microfluidic chips, new devices based on a co-flow regime were fabricated by microscale 3D printing via projection microstereoscopic lithography and were applied to produce single emulsion and double emulsion. The results showed that monodisperse water-in-oil (W/O) and oil-in-water (O/W) single emulsion could be produced in the same device with a coefficient of variation (CV) less than 3%. The parallelized microfluidic device has 5 droplet generators and can generate different types of single emulsions with a CV of approximately 3%. Furthermore, double emulsion droplets could be produced without surface treatment. The development of micro 3D printing provides a new way of microfluidics emulsion formation in food, especially for double emulsion formation, which has the great advantage of no surface treatment. These devices provide considerable support for further commercial application of droplet microfluidics. • Using micro 3D printing to develop microfluidic device based on the co-flow regime. • Different types of emulsions can be generated on the same device. • The device can realize the generation of double emulsion without surface treatment.

Microfluidic formation of highly monodispersed multiple cored droplets using needle-based system in parallel mode.

Scale-up in droplet microfluidics achieved by increasing the number of devices running in parallel or increasing the droplet makers in the same device can compromise the narrow droplet-size distribution, or requires high fabrication cost, when glass- or polymer-based microdevices are used. This paper reports a novel way using parallelization of needle-based microfluidic systems to form highly monodispersed droplets with enhanced production rates yet in cost-effective way, even when forming higher order emulsions with complex inner structure. Parallelization of multiple needle-based devices could be realized by applying commercially available two-way connecters and 3D-printed four-way connectors. The production rates of droplets could be enhanced around fourfold (over 660 droplets/min) to eightfold (over 1300 droplets/min) by two-way connecters and four-way connectors, respectively, for the production of the same kind of droplets than a single droplet maker (160 droplets/min). Additionally, parallelization of four-needle sets with each needle specification ranging from 34G to 20G allows for simultaneous generation of four groups of PDMS microdroplets with each group having distinct size yet high monodispersity (CV < 3%). Up to six cores can be encapsulated in double emulsion using two parallelly connected devices via tuning the capillary number of middle phase in a range of 1.31 × 10-4 to 4.64 × 10-4 . This study leads to enhanced production yields of droplets and enables the formation of groups of droplets simultaneously to meet extensive needs of biomedical and environmental applications, such as microcapsules with variable dosages for drug delivery or drug screening, or microcapsules with wide range of absorbent loadings for water treatment.

Controlled Microfluidic Synthesis of Biological Stimuli-Responsive Polymer Nanoparticles.

Microfluidic flow-directed self-assembly of biological stimuli-responsive block copolymers is demonstrated with dual-location cleavable linkages at the junction between hydrophilic and hydrophobic blocks and on pendant group within the hydrophobic blocks. On-chip self-assembly within a two-phase microfluidic reactor forms various "DualM" polymer nanoparticles (PNPs), including cylinders and multicompartment vesicles, with sizes and morphologies that are tunable with manufacturing flow rate. Complex kinetically trapped intermediates between shear-dependent states provide the most detailed mechanism to date of microfluidic PNP formation in the presence of flow-variable high shear. Glutathione (GSH)-triggered changes in PNP size and internal structure depend strongly on the initial flow-directed size and internal structure. Upon incubation in GSH, flow-directed PNPs with smaller average sizes showed a faster hydrodynamic size increase (attributed to junction cleavage) and those with higher excess Gibbs free energy showed faster inner compartment growth (attributed to pendant cleavage). These results demonstrate that the combination of chemical control of the location of biologically responsive linkages with microfluidic shear processing offers promising routes for tunable "smart" polymeric nanomedicines.

The Role of the BMP Pathway in Sustaining CML Stem Cells in the Bone Marrow Niche

Despite improved patient outcome using tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) patients require life-long treatment due to leukemic stem cell (LSC) persistence. LSCs reside together with mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) in the bone marrow (BM) niche, which they modify to their advantage whilst impairing normal hematopoiesis. To date it has proved difficult to understand how LSCs both dominate and alter the niche, and to effectively target LSCs with current therapies. Recent studies have shown intrinsic and extrinsic deregulation of the bone morphogenetic protein (BMP) pathway in CML. These cells show altered stem cell fate, persistence, and response to BMP receptor (BMPR) antagonists, which affect cell behavior including cell cycle, apoptosis, and expansion (Laperrousaz et al. 2013; Grockowiak et al. 2017; Zylbersztejn et al. 2018; Toofan et al. 2018). We compared TKIs alone and in combination with a BMPR inhibitor to gain improved insights into BCR-ABL1 dependent and independent regulatory mechanisms within the niche environment using this therapeutic approach. K562 CML cell line and CML CD34+ primary cells were used in this study in combination with HS5 stromal cell co-culture. CML cells were treated with single or combination treatments of imatinib, the dual SRC-ABL1 TKI saracatinib, and the BMPR inhibitor dorsomorphin for 4h or 72h with and without BMP4 stimulation/co-culture. HSC and LSC interactions were also investigated using our artificial 3D BM niche model which comprises of magnetically levitated MSC spheroids embedded in medical-grade collagen type I, mimicking the BM biological and mechanical microenvironment, along with a high throughput microfluidic MSC spheroid formation system for drug testing. Kinase screens were performed on CML CD34+ cells using a chip-based microarray assay (PamGene) following 4h drug treatments. Phosphorylation data were then utilized for upstream kinase and pathway analysis using the metacore platform. This analysis facilitated identification of proteins showing a change in expression of ≥0.5-fold across all (n=3) patient samples, which was validated by qPCR and immunoblotting. Fluidigm multiplex qPCR was utilized to assess changes in expression of early response, self-renewal and differentiation genes. Flow cytometry was performed to investigate apoptosis, cell cycle progression and proliferation, alongside colony assays of primary CD34+CP-CML samples (n=3) following treatment. We demonstrated a synergistic mode of action upon inhibition of the BMP pathway in combination with TKI treatment, resulting in increased apoptosis (p&lt; 0.001), altered cell cycle (G2-M, p&lt; 0.01), fewer cell divisions, and a reduction in CD34+cells. Primary patient samples displayed differential gene expression in relation to response for genes involved in cell cycle (CDKN1A, CDKN2B, RB1; p&lt; 0.05), self-renewal (PBX1; p&lt; 0.01) and cell survival (GATA1, CKIT, p&lt; 0.05). Kinase prediction analysis identified kinases involved in cell growth, development, differentiation, apoptosis, and cell-cell adhesion in treated sample lysates, with consequent pathway analysis highlighting transcription factors, ETS1, TP53 and C-MYC as main regulators across all common pathways. QPCR identified significant changes in expression of ETS1 (p&lt; 0.001) and C-MYC (p&lt; 0.01) following treatment. Within the top 10 deregulated pathways based on PamGene TK profiling we also identified GAB1 and GAB2 as common effectors, known to play an important role in growth and differentiation of myeloid cells, and which were demonstrated by immunoblotting to be considerably downregulated following 72h single and dual treatments in K562. Co-culture of CD34+ cells on stroma was chemo-protective, however dual treatment was still able to elicit strong anti-proliferative effects. We are currently investigating these promising findings in more detail using our 3D niche model and microfluidic spheroid platform. Taken together, these results provide vital insights into the mechanisms by which CML cells respond to current treatments, which is critical for improving therapeutic approaches and avoiding patient resistance or relapse. A combinatorial approach targeting the BMP pathway with BMP antagonists or small molecule inhibitors together with second-generation TKIs could open up new therapeutic possibilities. Disclosures No relevant conflicts of interest to declare.

Governing factors for preparation of silver nanoparticles using droplet-based microfluidic device.

Droplet-based microfluidic devices are now more than ever used for the synthesis of nanoparticles with low polydispersity and well-defined properties suitable for various industrial applications. Very small reaction volumes (microlitre to femtolitre) and short diffusion lengths, provide superior mixing efficiency and heat transport. Both play the dominant role in case of ultra-fast chemical reactions triggered upon reactant mixing, e.g. preparation of colloidal silver by reduction of silver salt. The high sensitivity of these systems to process variables makes otherwise more straightforward batch-wise production prone to suffer from inconsistency and poor reproducibility, which has an adverse effect on the reliability of production and further particle utilisation. This work presents a rigorous description of microfluidic droplet formation, reactant mixing, and nanoparticle synthesis using CFD simulations and experimental methods. The reaction mixture inside of droplets was homogenized in less than 40 milliseconds, which has been confirmed by simulations. Silver nanoparticles produced by droplet-based microfluidic chip showed superior to batch-wise preparation in terms of both particle uniformity and polydispersity.

Focused surface acoustic waves induced microdroplets generation and its application for microgels

We demonstrate a novel microdroplets generation method by using focused surface acoustic waves (FSAW). The method differs from previous work in the mechanism and the geometry structure of the chip, which is depend on FSAW rather than flow shearing. The acoustic radiation force arising from FSAW acts on the oil-water interface, breaking up the water into microdroplets whose size can be controlled by tuning the driving voltage and frequency of FSAW. This approach overcomes the limitation of microchannel structure and capillary number of the traditional microfluidic droplets formation methods, which enables a fully electrical control of microdroplets size, with a good uniformity. Further, the FSAW-induced microdroplets are used as templates to prepare microgels with uniform size, offering a new platform for the design and synthesis of monodispersed functional microspheres.

Passive and parallel microfluidic formation of droplet interface bilayers (DIBs) for measurement of leakage of small molecules through artificial phospholipid membranes

We present a passive microfluidic system for easy and rapid generation of Droplet Interface Bilayer pairs, each formed with two aqueous nanoliter droplets comprising controlled chemical composition. The system allows for rapid screening to quantify leakage of small molecules through artificial phospholipid bilayers. The droplets are generated, diluted and stored in-situ on the microfluidic chip. Our device comprises microfluidic Meter&Store (M&S) modules – hydrodynamic traps, which enable hard-wired operations on small – ca. 9 nL in volume – aqueous droplets including splitting, merging and derailing the droplets to side storage wells. Consequently, the droplets are locked and positioned next to each other and form bilayers at the point of contact between the nanoliter aqueous compartments. Additionally, a set of trap modules provides the possibility for in situ preparation of dilutions of a sample. We demonstrated the basic capacity of the trap-based system for formation of an array of 12 (controllably different) lipid bilayers in less than 5 min. Thanks to the small volumes of the droplets, the system is capable for monitoring the transport across the artificial membrane within a relatively short interval – opening the possibility to use dyes and alleviating the difficulty of parallel electrophysiological measurements. We use this functionality to prepare on-chip dilutions of small molecules and determine their permeation rates through the bilayer. Finally, we used the M&S system and calcium sensitive dyes to quantify the ion flux through the model α-hemolysin (αHL) nanopores.

Microfluidic Formation of Hydrogel Microcapsules with a Single Aqueous Core by Spontaneous Cross-Linking in Aqueous Two-Phase System Droplets.

We report a simple process to fabricate monodisperse tetra-arm poly(ethylene glycol) (tetra-PEG) hydrogel microcapsules with an aqueous core and a semipermeable hydrogel shell through the formation of aqueous two-phase system (ATPS) droplets consisting of a dextran-rich core and a tetra-PEG macromonomer-rich shell, followed by a spontaneous cross-end coupling reaction of tetra-PEG macromonomers in the shell. Different from conventional techniques, this process enables for the continuous production of hydrogel microcapsules from water-in-oil emulsion droplets under mild conditions in the absence of radical initiators and external stimuli such as heating and ultraviolet light irradiation. We find that rapid cross-end coupling reaction of tetra-PEG macromonomers in ATPS droplets in the range of pH from 7.4 to 7.8 gives hydrogel microcapsules with a kinetically arrested core-shell structure. The diameter and core-shell ratio of the microcapsules can be easily controlled by adjusting flow rates and ATPS compositions. On the other hand, the slow cross-end coupling reaction of tetra-PEG macromonomers in ATPS droplets at pH 7.0 and lower induces structural change from core-shell to Janus during the reaction, which eventually forms hydrogel microparticles with a thermodynamically stable crescent structure. We believe that these hydrogel microparticles with controlled structures can be used in biomedical fields such as cell encapsulation, biosensors, and drug delivery carriers for sensitive biomolecules.

Microfluidic formation of core-shell alginate microparticles for protein encapsulation and controlled release

Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigen + adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.

Microfluidic Formation of Coculture Tumor Spheroids with Stromal Cells As a Novel 3D Tumor Model for Drug Testing.

Three-dimensional (3D) tumor spheroids offer unprecedented capability for drug screening because of their unique features such as spatial 3D structure, relevant physiological responses, more complex intercellular network, and stroma-cancer cell interactions. Microfluidic technology provides a facile strategy to make uniform tumor spheroids with potential of high-throughput production. In this article, we develop a microfluidic approach to produce core-shell alginate particles, which allows the separate confinement of different cells in the core and shell structure. To reconstitute the complex tumor structure, we encapsulated tumor cells in the core and stromal fibroblast cells in the shell. These coculture tumor spheroids were applied for drug evaluation showing similar drug resistance as those prepared using conventional methods in well plates. These results demonstrated that our microfluidic approach are facile and versatile for making various tumor spheroids with uniform size but different components to better mimic tumor microenvironment. Moreover, the production rate of around 200 spheroids/min indicates the great potential of this approach for high-throughput drug screening.

Microfluidic Formation of Double-Stacked Planar Bilayer Lipid Membranes by Controlling the Water-Oil Interface.

This study reports double-stacked planar bilayer lipid membranes (pBLMs) formed using a droplet contact method (DCM) for microfluidic formation with five-layered microchannels that have four micro guide pillars. pBLMs are valuable for analyzing membrane proteins and modeling cell membranes. Furthermore, multiple-pBLM systems have broadened the field of application such as electronic components, light-sensors, and batteries because of electrical characteristics of pBLMs and membrane proteins. Although multiple-stacked pBLMs have potential, the formation of multiple-pBLMs on a micrometer scale still faces challenges. In this study, we applied a DCM strategy to pBLM formation using microfluidic techniques and attempted to form double-stacked pBLMs in micro-meter scale. First, microchannels with micro pillars were designed via hydrodynamic simulations to form a five-layered flow with aqueous and lipid/oil solutions. Then, pBLMs were successfully formed by controlling the pumping pressure of the solutions and allowing contact between the two lipid monolayers. Finally, pore-forming proteins were reconstituted in the pBLMs, and ion current signals of nanopores were obtained as confirmed by electrical measurements, indicating that double-stacked pBLMs were successfully formed. The strategy for the double-stacked pBLM formation can be applied to highly integrated nanopore-based systems.

Mechanical Reinforcement of Low‐Concentration Alginate Fibers by Microfluidic Embedding of Multiple Cores

AbstractThis paper presents mechanically reinforced low‐concentration alginate fibers by embedding inner cores of high‐concentration alginate. 3D structures by stacking multiple polydimethylsiloxane (PDMS) layers allow the microfluidic formation and control of the isolated cores in the continuous flow. The alginate hydrogel fibers are simply spun, and the compartments, central core, surrounding cores, and outer shell layer are successfully verified. The results demonstrate the great potential for the development of complex fibrous materials, particularly for biological applications, which require specific morphology and composition of the fibers.

Microfluidic formation of proteinosomes.

Herein we describe a novel microfluidic method for the generation of proteinosome micro-droplets, based on bovine serum albumin and glucose oxidase conjugated to PNIPAAm chains. The size of such water-in-oil droplets is regulated via control of the input reagent flow rate, with generated proteinosome populations exhibiting narrower size distributions than those observed when using standard bulk methodologies. Importantly, proteinosomes transferred from an oil to an aqueous-environment remain intact, become fully hydrated and exhibit an increase in average size. Moreover, functional proteinosomes prepared via microfluidics exhibit lower Km values and higher enzymatic activities than proteinosomes produced by bulk methodologies.

Charge-controlled microfluidic formation of lipid-based single- and multicompartment systems.

In this manuscript, we introduce a simple, off-the-shelf approach for the on-demand creation of giant unilamellar vesicles (GUVs) or multicompartment synthetic cell model systems in a high-throughput manner. To achieve this, we use microfluidics to encapsulate small unilamellar vesicles in block-copolymer surfactant-stabilized water-in-oil droplets. By tuning the charge of the inner droplet interface, adsorption of lipids can be either inhibited, leading to multicompartment systems, or induced, leading to the formation of droplet-stabilized GUVs. To control the charge density, we formed droplets using different molar ratios of an uncharged PEG-based fluorosurfactant and a negatively-charged PFPE carboxylic acid fluorosurfactant (Krytox). We systematically studied the transition from a multicompartment system to 3D-supported lipid bilayers as a function of lipid charge and Krytox concentration using confocal fluorescence microscopy, cryo-scanning electron microscopy and interfacial tension measurements. Moreover, we demonstrate a simple method to release GUVs from the surfactant shell and the oil phase into a physiological buffer - providing a remarkably high-yield approach for GUV formation. This widely applicable microfluidics-based technology will increase the scope of GUVs as adaptable cell-like compartments in bottom-up synthetic biology applications and beyond.

CFD analysis of microfluidic droplet formation in non–Newtonian liquid

A three-dimensional, volume-of-fluid (VOF) based CFD model is presented to investigate droplet formation in a microfluidic T-junction. Genesis of Newtonian droplets in non–Newtonian liquid is numerically studied and characterized in three different regimes, viz., squeezing, dripping and jetting. Various influencing factors such as, continuous and dispersed phase flow rates, interfacial tension, and non–Newtonian rheological parameters are analyzed to understand droplet formation mechanism. Droplet shape is reported by defining a deformation index. Near spherical droplets are realized in dripping and jetting regimes. However, plug shaped droplets are observed in squeezing regime. It is found that rheological parameters have significant effect on the droplet length, volume, and its formation regime. The formation frequency increases with increasing effective viscosity however, the droplet volume decreases. This work effectively provides the fundamental insights into microfluidic droplet formation characteristics in non–Newtonian liquids.

Femtosecond laser assisted fabrication of networked semi-occlusive microfluidic channel on fused silica glass surface

Networked semi-occlusive microfluidic was demonstrated via fabricating channel on the surface of the silica substrate using femtosecond laser direct writing (FLDW) followed by chemical etching and covering a thin layer of polydimethylsiloxane (PDMS) film on substrate. The microfluidic channel formation mechanism is identified as femtosecond laser irradiation leading to substrate material modification, and modified areas acquiring an increased solubility to hydrofluoric (HF) acid solution. The morphologies of networked microfluidic were characterized by using optical microscopy and scanning electronic microscopy. Furthermore, in order to test flowing characteristics of the microfluidic, we conducted the experiment of liquid injection.