Microfluidic on-chip production of microgels using combined geometries

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

10.21203/rs.3.rs-439280/v1 ◽

2021 ◽

Author(s):

Amirmohammad Sattari ◽

Sajad Janfaza ◽

Mohsen Mashhadi Keshtiban ◽

Nishat Tasnim ◽

Pedram Hanafizadeh ◽

...

Keyword(s):

Microfluidic Device ◽

Precursor Solution ◽

Average Diameter ◽

Continuous Phase ◽

Solution Viscosity ◽

Flow Conditions ◽

External Gelation ◽

Flow Geometry ◽

On Chip ◽

Spherical Droplets

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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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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Negative Pressure Provides Simple and Stable Droplet Generation in a Flow-Focusing Microfluidic Device

Micromachines ◽

10.3390/mi12060662 ◽

2021 ◽

Vol 12 (6) ◽

pp. 662

Author(s):

Nikita A. Filatov ◽

Anatoly A. Evstrapov ◽

Anton S. Bukatin

Keyword(s):

Microfluidic Device ◽

Negative Pressure ◽

Low Cost ◽

Control Valve ◽

Droplet Microfluidics ◽

Droplet Generation ◽

Electric Signal ◽

Absolute Pressure ◽

Flow Focusing ◽

Wide Range

Droplet microfluidics is an extremely useful and powerful tool for industrial, environmental, and biotechnological applications, due to advantages such as the small volume of reagents required, ultrahigh-throughput, precise control, and independent manipulations of each droplet. For the generation of monodisperse water-in-oil droplets, usually T-junction and flow-focusing microfluidic devices connected to syringe pumps or pressure controllers are used. Here, we investigated droplet-generation regimes in a flow-focusing microfluidic device induced by the negative pressure in the outlet reservoir, generated by a low-cost mini diaphragm vacuum pump. During the study, we compared two ways of adjusting the negative pressure using a compact electro-pneumatic regulator and a manual airflow control valve. The results showed that both types of regulators are suitable for the stable generation of monodisperse droplets for at least 4 h, with variations in diameter less than 1 µm. Droplet diameters at high levels of negative pressure were mainly determined by the hydrodynamic resistances of the inlet microchannels, although the absolute pressure value defined the generation frequency; however, the electro-pneumatic regulator is preferable and convenient for the accurate control of the pressure by an external electric signal, providing more stable pressure, and a wide range of droplet diameters and generation frequencies. The method of droplet generation suggested here is a simple, stable, reliable, and portable way of high-throughput production of relatively large volumes of monodisperse emulsions for biomedical applications.

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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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Toward a concept of the functional unit of mammalian skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.242.5.r411 ◽

1982 ◽

Vol 242 (5) ◽

pp. R411-R420 ◽

Cited By ~ 5

Author(s):

E. H. Bloch ◽

A. S. Iberall

Keyword(s):

Skeletal Muscle ◽

Functional Data ◽

Functional Unit ◽

Average Diameter ◽

Mammalian Skeletal Muscle ◽

Muscle Bundle ◽

Cross Sectional ◽

Maximum Area ◽

Motor End Plate ◽

Definition Of

The current concepts for the functional unit of mammalian skeletal muscle are reviewed and shown to lack components that are required for determining the unit. To secure a definition for the functional unit, requisite criteria were selected, and the manner by which these criteria were used to define the functional unit are discussed. For deriving a definition of the unit the following values were obtained: the unit is associated with the total length of the muscle fiber, which may achieve a maximum length of 60 cm; it exhibits an average diameter of 40 micrometers/fiber; it is associated with a capillary net whose length (arteriole to venule) is about 750-1,000 micrometers max; the net exhibits a capillary-to-fiber ratio for long capillaries of approximately 1-1.5:1, with a transverse capillaries occurring approximately every 150 micrometers; and it has a fiber-to-motor end plate ratio of 1:1. The correlation between anatomic data and functional data indicate that a functional unit of muscle is delimited by about 1 mm2 of the cross-sectional area of a muscle bundle, since this is the maximum area under autonomic control of its particular arteriolar blood supply, the metabolic throttle that determines the power being expended by the muscle bundle.

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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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The Combined Effects of Co-Culture and Substrate Mechanics on 3D Tumor Spheroid Formation within Microgels Prepared via Flow-Focusing Microfluidic Fabrication

Pharmaceutics ◽

10.3390/pharmaceutics10040229 ◽

2018 ◽

Vol 10 (4) ◽

pp. 229 ◽

Cited By ~ 11

Author(s):

Dongjin Lee ◽

Chaenyung Cha

Keyword(s):

Mechanical Properties ◽

Cell Culture ◽

Microfluidic Device ◽

3D Cell Culture ◽

Breast Adenocarcinoma ◽

Adherent Cell ◽

Flow Focusing ◽

Spheroid Formation ◽

3D Scaffold ◽

Tumor Spheroids

Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as well as basic scientific endeavors, as several cell types can efficiently form spheroids by themselves in both suspension and adherent cell cultures. However, it is more desirable to utilize a 3D scaffold with tunable properties to create more physiologically relevant tumor spheroids as well as optimize their formation. In this study, bioactive spherical microgels supporting 3D cell culture are fabricated by a flow-focusing microfluidic device. Uniform-sized aqueous droplets of gel precursor solution dispersed with cells generated by the microfluidic device are photocrosslinked to fabricate cell-laden microgels. Their mechanical properties are controlled by the concentration of gel-forming polymer. Using breast adenocarcinoma cells, MCF-7, the effect of mechanical properties of microgels on their proliferation and the eventual spheroid formation was explored. Furthermore, the tumor cells are co-cultured with macrophages of fibroblasts, which are known to play a prominent role in tumor physiology, within the microgels to explore their role in spheroid formation. Taken together, the results from this study provide the design strategy for creating tumor spheroids utilizing mechanically-tunable microgels as 3D cell culture platform.

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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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Is an empirical approach to performing access in pediatric surgery in children safe?

Paediatric Surgery Ukraine ◽

10.15574/ps.2020.69.43 ◽

2020 ◽

pp. 43-50

Author(s):

V.S. Konoplitskiy ◽

◽

R.V. Shavliuk ◽

Keyword(s):

Anal Sphincter ◽

External Anal Sphincter ◽

Pilonidal Disease ◽

Muscle Fibers ◽

External Sphincter ◽

Average Diameter ◽

Modern World ◽

Anal Sphincters ◽

Cross Sectional ◽

Surgical Interventions

Objective: to determine the topical localization of the structural components of the anal sphincter and to formulate the basic postulates of the formation of safe anatomical access in pilonidal disease surgery in children. Materials and methods: the study was conducted on the corpses of 10 children who had no lifelong pathology of the sacrococcygeal region and pelvis aged 12 to 17 years, including 5 girls and 5 boys. Soft tissue columns 1 cm wide and up to 5 cm long were prepared at a distance of 1 cm from the anus by 12 h, 3 h, 6 h and 9 h according to the dial in the back position. After preparation and fixation of the drugs, their staining was performed and cross-sections of anal sphincters 5–7 μm thick were made. The analysis of the received morphometric data is carried out. The results of the study: it was found that the cross-sectional area of the bundle of muscle fibers of the external sphincter of the anus on average in adolescents ranged from 448±32 μm2 to 412±24 μm2. The diameter of its muscle fibers was 13.02±1.56 μm, and the bulk density of muscle fibers is 96.12±1.34%. Regarding the length of the internal anal sphincter, it was found that it is almost the same in different areas and is 1.3±0.03 at the level of 3 and 12 hours, 1.3±0.07 at the level of 6 hours and 1.2±0.03 at the level of 9 hours. In the study of the linear dimensions of the length of different portions of external anal sphincter in certain places of the biopsy revealed a predominance of parameters that were determined at 6 hours, respectively, 5.7±0.06 cm against 4.3±0.04 cm at 3 hours, and 12 hours, respectively 5.1±0.06 cm against 4.3±0.03 cm at 9 years. The thickness of the external sphincter of the anus at 6 hours, respectively 26.7±0.61 mm against 18.5±0.19 mm at 3 hours, (<0.01) and 12 hours, respectively 23.9±0.33 mm against 18.4±0.19 mm at 9 hours. Diameters of separate muscular fibers and bundles were explored. It is established that the average diameter of a muscle fiber makes 13.7±0.18 microns, and the average diameter of a muscular bundle is equal to 435.9±5.15 microns. Conclusions. 1. Existing anatomical descriptions of anal sphincters need in the modern world more thorough research to prevent their injury during surgery. 2. The external anal sphincter has the spatial form of the three-storeyed oval structure extended in the front-back direction with dominance of the caudal muscular portion. 3. When performing radical surgical interventions for pilonidal disease in children by cleft-lift method, it is necessary to complete the edge of surgical access at a distance of not less than 3 cm to the edge of the anal sphincter. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: pilonidal disease, children, morphometry, surgical intervention.

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