A hydrodynamic flow focusing microfluidic device for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride

This work describes a novel microfluidic method to generate uniform water-in-oil (W/O) microspheres using the phase separation technique. Axiomatic design theory (ADT) was employed for the conceptual design of microchannel systems, and ADT verified that the proposed microfluidic system is a decoupled design. The integration of hydrodynamic flow focusing method and crossflow method is realized in a microfluidic device with oil phase and aqueous phase. The immiscible fluids are fed by continuous air pressure. By the hydrodynamic flow focusing method, the width of the dispersed focused aqueous phase is controlled. The focused flow enters T-junction geometry downstream, and the crossflow interferes with the focused flow. By varying the applied pressure to the crossflow, the W/O microspheres are formed at the T-junction. Based on this approach, the size of the W/O microspheres can be successfully controlled from 16 μm to 35 μm in diameter within about 5% of variation. The present method has advantages such as good sphericity, few satellite droplets, active control of the microsphere diameter, and high throughput with the simple and low cost process. To achieve the promising results, this integrating method reveals high potential for production of polymer based microspheres.

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A 3D hydrodynamic flow-focusing device for cell sorting

Microfluidics and Nanofluidics ◽

10.1007/s10404-021-02425-y ◽

2021 ◽

Vol 25 (3) ◽

Author(s):

Xiaofei Yuan ◽

Andrew Glidle ◽

Hitoshi Furusho ◽

Huabing Yin

Keyword(s):

Cell Sorting ◽

Control Strategies ◽

Three Dimensional ◽

Hydrodynamic Flow ◽

Proof Of Concept ◽

Flow Focusing ◽

Hydrodynamic Focusing ◽

Cell Handling ◽

Fluid Flow Control ◽

High Degree

AbstractOptical-based microfluidic cell sorting has become increasingly attractive for applications in life and environmental sciences due to its ability of sophisticated cell handling in flow. The majority of these microfluidic cell sorting devices employ two-dimensional fluid flow control strategies, which lack the ability to manipulate the position of cells arbitrarily for precise optical detection, therefore resulting in reduced sorting accuracy and purity. Although three-dimensional (3D) hydrodynamic devices have better flow-focusing characteristics, most lack the flexibility to arbitrarily position the sample flow in each direction. Thus, there have been very few studies using 3D hydrodynamic flow focusing for sorting. Herein, we designed a 3D hydrodynamic focusing sorting platform based on independent sheath flow-focusing and pressure-actuated switching. This design offers many advantages in terms of reliable acquisition of weak Raman signals due to the ability to precisely control the speed and position of samples in 3D. With a proof-of-concept demonstration, we show this 3D hydrodynamic focusing-based sorting device has the potential to reach a high degree of accuracy for Raman activated sorting.

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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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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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Design, characterization and application of a novel mono-layer pin-microvalve for microfluidic devices

RSC Advances ◽

10.1039/c4ra02233e ◽

2014 ◽

Vol 4 (46) ◽

pp. 24394-24398 ◽

Cited By ~ 1

Author(s):

Mahyar Nasabi ◽

Masoomeh Tehranirokh ◽

Francisco Javier Tovar-Lopez ◽

Abbas Kouzani ◽

Khashayar Khoshmanesh ◽

...

Keyword(s):

Microfluidic Devices ◽

Hydrodynamic Flow ◽

Flow Focusing ◽

Mono Layer

We introduce a novel manual pin-valve which can operate in both analogue (partially close) and digital (on/off) states. We also demonstrate implementation of this pin-valve in a hydrodynamic flow focusing (HFF) device.

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3D FOCALIZATION MICROFLUIDIC DEVICE BUILT WITH LTCC TECHNOLOGY FOR NANOPARTICLE GENERATION USING NANOPRECIPITATION ROUTE

Additional Conferences (Device Packaging HiTEC HiTEN & CICMT) ◽

10.4071/cicmt-tha13 ◽

2015 ◽

Vol 2015 (CICMT) ◽

pp. 000275-000280 ◽

Cited By ~ 2

Author(s):

Houari Cobas Gomez ◽

Mario Ricardo Gongora-Rubio ◽

Bianca Oliveira Agio ◽

Vanessa Tiemi Kimura ◽

Adriano Marim de Oliveira ◽

...

Keyword(s):

Microfluidic Device ◽

Chemical Process ◽

Chemical Processes ◽

Polydispersity Index ◽

Flow Focusing ◽

Enabling Technology ◽

Fine Chemistry ◽

Excellent Control ◽

Microsystem Technologies ◽

Nanoparticle Generation

Nanoprecipitation is a nanonization technique used for nanoparticle generation. Several fields, like pharmacology and fine chemistry, make use of such technique. Typically are used a bulky batch mechanical processes rendering high polydispersity index of generated nanoparticles, poorly particle size reproducibility and energy wasting. LTCC-based microsystem technologies allow the implementation of different unitary operations for chemical process, making it an enabling technology for the miniaturization of chemical processes. In fact, recently LTCC microfluidic reactors have been used to produce micro and nanoparticles with excellent control of size distribution and morphology. The present work provides a report on the performance of a 3D LTCC flow focusing Microfluidic device designed to fabricate polymeric nanocapsules for Hydrocortisone drug encapsulation, using nanoprecipitation route. Monodisperse Hydrocortisone nanocapsules were obtained with sizes (Tp) from 188.9 nm to 459.1 nm with polydispersity index (PDI) from 0.102 to 0.235.

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