Microfluidic on-chip Production of Alginate Hydrogels Using Double Co-flow Geometry

Abstract Microfluidic on-chip production of microgels employing external gelation has numerous biological and pharmaceutical applications, particularly for the encapsulation of delicate cargos, however, the on-chip production of microgels in microfluidic devices can be challenging due to problems such as clogging caused by accelerated progress in precursor solution viscosity. Here, we introduce a novel microfluidic design incorporating two consecutive co-flow geometries for microfluidic droplet generation. A shielding oil phase is employed to avoid emulsification and gelation stages from occurring simultaneously, thereby preventing clogging. The results revealed that the microfluidic device could generate highly monodispersed spherical droplets (coefficient of variation < 3%) with an average diameter in the range of 60–200 μm. Additionally, it was demonstrated that the device could appropriately create a shelter of the oil phase around the inner aqueous phase regardless of the droplet formation regime and flow conditions. The ability of the proposed microfluidic device in the generation of microgels was validated by producing alginate microgels utilizing an aqueous solution of calcium chloride as the continuous phase.

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Microfluidic on-chip production of microgels using combined geometries

Scientific Reports ◽

10.1038/s41598-021-81214-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hamed Shieh ◽

Maryam Saadatmand ◽

Mahnaz Eskandari ◽

Dariush Bastani

Keyword(s):

Microfluidic Device ◽

Precursor Solution ◽

Average Diameter ◽

Solution Viscosity ◽

Dispersed Phase ◽

Sudden Increase ◽

Flow Focusing ◽

Cross Sectional ◽

External Gelation ◽

On Chip

AbstractMicrofluidic on-chip production of microgels using external gelation can serve numerous applications that involve encapsulation of sensitive cargos. Nevertheless, on-chip production of microgels in microfluidic devices can be challenging due to problems induced by the rapid increase in precursor solution viscosity like clogging. Here, a novel design incorporating a step, which includes a sudden increase in cross-sectional area, before a flow-focusing nozzle was proposed for microfluidic droplet generators. Besides, a shielding oil phase was utilized to avoid the occurrence of emulsification and gelation stages simultaneously. The step which was located before the flow-focusing nozzle facilitated the full shielding of the dispersed phase due to 3-dimensional fluid flow in this geometry. The results showed that the microfluidic device was capable of generating highly monodispersed spherical droplets (CV < 2% for step and CV < 5% for flow-focusing nozzle) with an average diameter in the range of 90–190 μm, both in step and flow-focusing nozzle. Moreover, it was proved that the device could adequately create a shelter for the dispersed phase regardless of the droplet formation locus. The ability of this microfluidic device in the production of microgels was validated by creating alginate microgels (with an average diameter of ~ 100 μm) through an external gelation process with on-chip calcium chloride emulsion in mineral oil.

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On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures

Micromachines ◽

10.3390/mi10120840 ◽

2019 ◽

Vol 10 (12) ◽

pp. 840 ◽

Cited By ~ 4

Author(s):

Tao Yue ◽

Na Liu ◽

Yuanyuan Liu ◽

Yan Peng ◽

Shaorong Xie ◽

...

Keyword(s):

Microfluidic Device ◽

Efficient Method ◽

High Efficiency ◽

Flow Conditions ◽

Artificial Blood ◽

Assembly Method ◽

Artificial Blood Vessels ◽

Direct Fabrication ◽

Potential Applications ◽

On Chip

Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based on direct fabrication and assembly inside a microfluidic device. This four-layer microfluidic device has two separate inlets for fabricating various microstructures. We have achieved alternating-layered microtubes by controlling the fabrication, flow, and assembly time of each microstructure, and as well, double-layered microtubes have been built by a two-step assembly method. Modifications of both the inner and outer layers was successfully demonstrated, and the flow conditions during the on-chip assembly were evaluated and optimized. Each microtube was successfully constructed within several minutes, showing the potential applications of the presented method for building engineered vascular-like microstructures with high efficiency.

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Microbubble Array as a Versatile Tool for On-Chip Worm Processing

Volume 9: Micro- and Nano-Systems Engineering and Packaging, Parts A and B ◽

10.1115/imece2012-87132 ◽

2012 ◽

Author(s):

Gan Yu ◽

Ali Hashmi ◽

Yuhao Xu ◽

Hyuck-Jin Kwon ◽

Xiaolin Chen ◽

...

Keyword(s):

Microfluidic Device ◽

Trapping Efficiency ◽

Flow Conditions ◽

C Elegans ◽

Novel Technique ◽

Versatile Tool ◽

On Chip ◽

First Time

In this study, we present a novel technique for achieving precise trapping, enrichment and manipulation of C. elegans using an array of oscillating microbubbles in a simple microfluidic device. We demonstrate a high trapping efficiency and enrichment of C. elegans characterized by the flow conditions. We also demonstrate for the first time an on-chip manipulation of the pathways of a single C. elegans through temporal actuation of bubbles.

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Design and Manufacturing of a Disposable, Cyclo-Olefin Copolymer, Microfluidic Device for a Biosensor †

Sensors ◽

10.3390/s19051178 ◽

2019 ◽

Vol 19 (5) ◽

pp. 1178 ◽

Cited By ~ 2

Author(s):

Jorge Prada ◽

Christina Cordes ◽

Carsten Harms ◽

Walter Lang

Keyword(s):

Microfluidic Device ◽

Heating Temperature ◽

Low Cost ◽

Reaction Chamber ◽

Microfluidic System ◽

Heating Process ◽

Design And Manufacturing ◽

On Chip ◽

Working Parameters ◽

Auto Fluorescence

This contribution outlines the design and manufacturing of a microfluidic device implemented as a biosensor for retrieval and detection of bacteria RNA. The device is fully made of Cyclo-Olefin Copolymer (COC), which features low auto-fluorescence, biocompatibility and manufacturability by hot-embossing. The RNA retrieval was carried on after bacteria heat-lysis by an on-chip micro-heater, whose function was characterized at different working parameters. Carbon resistive temperature sensors were tested, characterized and printed on the biochip sealing film to monitor the heating process. Off-chip and on-chip processed RNA were hybridized with capture probes on the reaction chamber surface and identification was achieved by detection of fluorescence tags. The application of the mentioned techniques and materials proved to allow the development of low-cost, disposable albeit multi-functional microfluidic system, performing heating, temperature sensing and chemical reaction processes in the same device. By proving its effectiveness, this device contributes a reference to show the integration potential of fully thermoplastic devices in biosensor systems.

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BslA-stabilized emulsion droplets with designed microstructure

Interface Focus ◽

10.1098/rsfs.2016.0124 ◽

2017 ◽

Vol 7 (4) ◽

pp. 20160124 ◽

Cited By ~ 4

Author(s):

Keith M. Bromley ◽

Cait E. MacPhee

Keyword(s):

Structural Integrity ◽

Melting Process ◽

Continuous Phase ◽

Central Component ◽

Emulsion Droplet ◽

Emulsion Droplets ◽

Elastic Film ◽

Air Water Interface ◽

Droplet Morphology ◽

Spherical Droplets

Emulsions are a central component of many modern formulations in food, pharmaceuticals, agrichemicals and personal care products. The droplets in these formulations are limited to being spherical as a consequence of the interfacial tension between the dispersed phase and continuous phase. The ability to control emulsion droplet morphology and stabilize non-spherical droplets would enable the modification of emulsion properties such as stability, substrate binding, delivery rate and rheology. One way of controlling droplet microstructure is to apply an elastic film around the droplet to prevent it from relaxing into a sphere. We have previously shown that BslA, an interfacial protein produced by the bacterial genus Bacillus , forms an elastic film when exposed to an oil- or air–water interface. Here, we highlight BslA's ability to stabilize anisotropic emulsion droplets. First, we show that BslA is capable of arresting dynamic emulsification processes leading to emulsions with variable morphologies depending on the conditions and emulsification technique applied. We then show that frozen emulsion droplets can be manipulated to induce partial coalescence. The structure of the partially coalesced droplets is retained after melting, but only when there is sufficient free BslA in the continuous phase. That the fidelity of replication can be tuned by adjusting the amount of free BslA in solution suggests that freezing BslA-stabilized droplets disrupts the BslA film. Finally, we use BslA's ability to preserve emulsion droplet structural integrity throughout the melting process to design emulsion droplets with a chosen shape and size.

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Preparation and properties of wet-spun microcomposite filaments from cellulose nanocrystals and alginate using a microfluidic device

BioResources ◽

10.15376/biores.16.3.5780-5793 ◽

2021 ◽

Vol 16 (3) ◽

pp. 5780-5793

Author(s):

Ji-Soo Park ◽

Chan-Woo Park ◽

Song-Yi Han ◽

Eun-Ah Lee ◽

Azelia Wulan Cindradewi ◽

...

Keyword(s):

Tensile Properties ◽

Sodium Alginate ◽

Calcium Chloride ◽

Microfluidic Device ◽

Cellulose Nanocrystals ◽

Average Diameter ◽

Coagulation Bath ◽

Al Content ◽

Orientation Index ◽

Cacl2 Solution

Cellulose nanocrystals (CNCs) were wet-spun in a coagulation bath for the fabrication of microfilaments, and the effect of sodium alginate (AL) addition on the wet-spinnability and properties of the microcomposite filament was investigated. The CNC suspension exhibited excellent wet-spinnability in calcium chloride (CaCl2) solution, and the addition of AL in CNC suspension resulted in the enhancement of the wet-spinnability of CNCs. As the AL content increased from 3% to 10%, the average diameter of the microcomposite filament decreased, and its tensile properties deteriorated. The increased spinning rate caused an increase in the orientation index of CNCs, resulting in an improvement in the tensile properties of the microcomposite filament.

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Micropipette-Based Microfluidic Device for Monodisperse Microbubbles Generation

Micromachines ◽

10.3390/mi9080387 ◽

2018 ◽

Vol 9 (8) ◽

pp. 387

Author(s):

Carlos Toshiyuki Matsumi ◽

Wilson José da Silva ◽

Fábio Kurt Schneider ◽

Joaquim Miguel Maia ◽

Rigoberto E. M. Morales ◽

...

Keyword(s):

Electric Fields ◽

Microfluidic Device ◽

Soft Lithography ◽

Low Cost ◽

Characteristic Curve ◽

Microfluidic Devices ◽

Average Diameter ◽

Internal Diameter ◽

Medical Diagnostic ◽

Average Size

Microbubbles have various applications including their use as carrier agents for localized delivery of genes and drugs and in medical diagnostic imagery. Various techniques are used for the production of monodisperse microbubbles including the Gyratory, the coaxial electro-hydrodynamic atomization (CEHDA), the sonication methods, and the use of microfluidic devices. Some of these techniques require safety procedures during the application of intense electric fields (e.g., CEHDA) or soft lithography equipment for the production of microfluidic devices. This study presents a hybrid manufacturing process using micropipettes and 3D printing for the construction of a T-Junction microfluidic device resulting in simple and low cost generation of monodisperse microbubbles. In this work, microbubbles with an average size of 16.6 to 57.7 μm and a polydispersity index (PDI) between 0.47% and 1.06% were generated. When the device is used at higher bubble production rate, the average diameter was 42.8 μm with increased PDI of 3.13%. In addition, a second-order polynomial characteristic curve useful to estimate micropipette internal diameter necessary to generate a desired microbubble size is presented and a linear relationship between the ratio of gaseous and liquid phases flows and the ratio of microbubble and micropipette diameters (i.e., Qg/Ql and Db/Dp) was found.

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Conformal Coating by Liquid Route on Three-Dimensional Topology

10.20944/preprints201809.0071.v1 ◽

2018 ◽

Author(s):

Poirot Nathalie ◽

Raynal Pierre-Ivan

Keyword(s):

Spin Coating ◽

Three Dimensional ◽

Precursor Solution ◽

Solution Viscosity ◽

Chemical Solution ◽

New Approach ◽

Conformal Coating ◽

Si Substrates ◽

Aspect Ratios ◽

Post Annealing

We demonstrated a new approach to the production of three-dimensional-coated patterns using liquid route. Metallic perovskite oxides were coated onto three-dimensional (3D) microstructured substrates with different aspect ratios. The success of the method relies on the solution viscosity monitored by adding viscous liquid. The process of oxide thin films consists in three steps: preparing the precursor solution, coating the solution by spin-coating process onto three-dimensional-Si substrates and post-annealing. The chemical solution 3D-coating is conformal.

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