fabricating-high-viscosity-droplets-using-microfluidic-capillary

Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure

The generation of monodisperse droplets with high viscosity has always been a challenge in droplet microfluidics. Here, we demonstrate a phase-inversion ...

Tsinghua University

Mass-transfer-induced multistep phase separation was found in emulsion droplets. The agent system consists of a monomer (ethoxylated trimethylolpropane triacrylate, ETPTA), an oligomer (polyethylene glycol diacrylate, PEGDA 700), and water. The PEGDA in the separated layers offered partial miscibility of all the components throughout the multistep phase-separation procedure, which was terminated by the depletion of PEGDA in the outermost layer. The number of separated portions was determined by the initial PEGDA content, and the initial droplet size influenced the mass-transfer process and consequently determined the sizes of the separated layers. The resultant multilayered emulsions were demonstrated to offer an orderly temperature-responsive release of the inner cores. Moreover, the emulsion droplets can be readily solidified into onionlike microspheres by ultraviolet light curing, providing a new strategy in designing particle structures. 

Mass-Transfer-Induced Multistep Phase Separation in Emulsion Droplets: Toward Self-Assembly Multilayered Emulsions and Onionlike Microspheres.

Fluids containing high concentration polymers, sols, nanoparticles, etc., usually have high viscosities, and high-viscosity fluids are difficult to be encapsulated into uniform droplets. Here we report a surface-controlled breakup method to generate droplets directly from various aqueous and nonaqueous fluids with viscosities of 1.0 to 11.9 Pa s and a dispersed-to-continuous viscosity ratio up to 1000, whereas the volume fraction of droplets up to 50% can be achieved. It provides a straightforward method to encapsulate high viscosity fluids, in a well-controlled manner in the rapid developing droplet-based applications, including materials synthesis, drug delivery, cell assay, bioengineering, etc.

Microfluidic Generation of High-Viscosity Droplets by Surface-Controlled Breakup of Segment Flow.

Phase separation occurs in emulsion droplets containing poly (ethylene glycol) diacrylate (PEGDA), glycerol, and ethanol to form a glycerol-in-PEGDA structure, and the phase separation process is found to depend on the droplet size. The mechanism of this size-dependent phase separation is dependent on the droplet sizes changing the phase separation time by changing the evaporation speed of mutual solvent ethanol, and the relationship between the separation time T and the droplet diameter D is derived as T≈D , which has been validated by experiment results. According to this finding, the structures of the droplets can be designed by applying UV curing at different stages of the phase separation, and the monodispersity of droplets is necessary to achieve polymerized particles with the same structure.

Size-Dependent Phase Separation in Emulsion Droplets.

Three-dimensional (3D) bioprinting is a novel technology utilizing biocompatible materials, cells, drugs, etc. as basic microcomponents to form 3D artificial structures and is believed as a promising method for regenerative medicine. Droplet-based bioprinting can precisely generate microspheres and manipulate them into organized structures with high fidelity. Biocompatible hydrogels are usually used as bioinks in 3D bioprinting, however, the viscosity of the bioink could be increased due to the additives such as cells, drugs, nutrient factors and other functional polymers in some particular applications, making it difficult to form monodispersed microspheres from high-viscosity bioink at the orifice of the nozzle. In this work, we reported a novel microfluidic-based printing nozzle to prepare monodispersed microspheres from high-viscosity bioink using the phase-inversion method. Different flowing conditions can be achieved by changing the flow rates of the fluids to form monodispersed solid and hollow microspheres using the same nozzle. The diameter of the microspheres can be tuned by changing the flow rate ratio and the size distribution of the microspheres is narrow. The prepared calcium alginate microspheres could also act as micro-carriers in drug delivery.

Fabrication of Microspheres from High-Viscosity Bioink Using a Novel Microfluidic-Based 3D Bioprinting Nozzle.

The rapid development of portable precision detection methods and the crisis of insufficient blood supply worldwide has led scientists to study mechanical visualization features beyond the biochemical properties of erythrocytes. Combined evaluation of currently known biochemical biomarkers and mechanical morphological biomarkers will become the mainstream of single-cell detection in the future. To explore the mechanical morphology of erythrocytes, a microfluidic capillary system was constructed in vitro, with flow velocity and glucose concentration as the main variables, and the morphology and ability of erythrocytes to recover from deformation as the main objects of analysis. We showed the mechanical distortion of erythrocytes under various experimental conditions. Our results showed that glucose plays important roles in improving the ability of erythrocytes to recover from deformation and in repairing the damage caused to the cell membrane during the repeated squeeze process. These protective effects were also confirmed in in vivo experiments. Our results provide visual detection markers for single-cell chips and may be useful for future studies in cell aging.

Role of glucose in the repair of cell membrane damage during squeeze distortion of erythrocytes in microfluidic capillaries.

Fabrication of a blood-repellent surface is essential for implantable or interventional medical devices to avoid thrombosis which can induce several serious complications. In this research, a novel micropatterned surface was fabricated  a facile and cost-effective method, and then, the  and  blood-repellent performances of the controllable superhydrophobic surface were systematically evaluated. First, a facile and cost-effective strategy was proposed to fabricate a controllable superhydrophobic surface on a medically pure titanium substrate using an ultraviolet laser process, ultrasonic acid treatment, and chemical modification. Second, the superhydrophobicity, durability, stability, and corrosion resistance of the superhydrophobic surface were confirmed with advanced testing techniques, which display a high contact angle, low adhesion to water and blood, and excellent resistant element precipitation. Third, the platelet-rich plasma and whole blood were applied to evaluate the hemocompatibility of the superhydrophobic surface by means of an  experiment, and no blood cell activation or aggregation was observed on the superhydrophobic surface. Finally, hollow tubes with an inner superhydrophobic surface were implanted into the left carotid artery of rabbits for 2 weeks to verify the biocompatibility . The superhydrophobic surface could effectively eliminate blood cell adhesion and thrombosis. No obvious inflammation or inordinate proliferation was found by histological analysis. This research provides a facile and cost-effective strategy to prepare a blood-repellent surface, which may have promising applications in implanted biomedical devices.

 Blood-Repellent Performance of a Controllable Facile-Generated Superhydrophobic Surface.

In this work, we used a co-flow microfluidic device with an injection and a collection tube to generate droplets with different layers due to phase separation. The phase separation system consisted of poly(ethylene glycol) diacrylate 700 (PEGDA 700), PEGDA 250, and sodium alginate aqueous solution. When the mixture droplets formed in the outer phase, PEGDA 700 in the droplets would transfer into the outer aqueous solution, while PEGDA 250 still stayed in the initial droplet, breaking the miscibility equilibrium of the mixture and triggering the phase separation. As the phase separation proceeded, new cores emerged in the droplets, gradually forming the second and third layers. Emulsion droplets with different layers were polymerized under ultraviolet (UV) irradiation at different stages of phase separation to obtain microspheres. Microspheres with different layers showed various release behaviors in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release rate decreased with the increase in the number of layers, which showed a potential application in sustained drug release.

Fabrication of Multi-Layered Microspheres Based on Phase Separation for Drug Delivery.

In remanufacturing engineering, cleaning is the key factor for subsequent blank inspection and parts repair. Molten salt has the characteristics of low viscosity, good fluidity, and strong chemical stability. Salt bath cleaning can be comprehensively applied to remove various organic pollutants. Molten salt has the function of self-cleaning. The dirt in the cleaning pool can be decomposed and reused. Moreover, the waste molten salt is massive, and the waste residue is easy to treat. The formation and adsorption mechanism of carbon deposition was explored, and the formation mechanism of carbon deposition was verified by experiments. Then, the existing formula was improved by mixing experiment and compared with the current cleaning method; the cleaning effect was excellent. A new molten salt formula is proposed on the basis of the research on solar thermal storage medium. The composition percentage and the optimal process parameters of the new molten salt formula were determined on the basis of the experimental design of mixture. The cleaning effect of the new formula is good.

Article	Year
Mass-Transfer-Induced Multistep Phase Separation in Emulsion Droplets: Toward Self-Assembly Multilayered Emulsions and Onionlike Microspheres. Langmuir : the ACS journal of surfaces and colloids\| PubMed ID: 27427849	2016
Microfluidic Generation of High-Viscosity Droplets by Surface-Controlled Breakup of Segment Flow. ACS applied materials & interfaces\| PubMed ID: 28589716	2017
Size-Dependent Phase Separation in Emulsion Droplets. Chemphyschem : a European journal of chemical physics and physical chemistry\| PubMed ID: 29399932	2018
Fabrication of Microspheres from High-Viscosity Bioink Using a Novel Microfluidic-Based 3D Bioprinting Nozzle. Micromachines\| PubMed ID: 32674334
Role of glucose in the repair of cell membrane damage during squeeze distortion of erythrocytes in microfluidic capillaries. Lab on a chip\| PubMed ID: 33432946
Blood-Repellent Performance of a Controllable Facile-Generated Superhydrophobic Surface. ACS applied materials & interfaces\| PubMed ID: 34102844
Fabrication of Multi-Layered Microspheres Based on Phase Separation for Drug Delivery. Micromachines\| PubMed ID: 34205458
Carbon deposition mechanism of molten salt cleaning and optimization of multicomponent molten salt formula for remanufacturing. Science progress\| PubMed ID: 34261352	2021

Jia Man

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