A Comprehensive Review of Three-Dimensional Neuro-Organoids and Engineering Brain-on-a-Chip Microfluidic Devices

2021 ◽  
Author(s):  
Lamees El Nihum ◽  
Nandan Shettigar ◽  
Debjyoti Banerjee ◽  
Robert Krencik

Abstract The focus of this review is to describe advances in three-dimensional (3D) organoids reported in the literature with an emphasis on the engineering of microfluidic device platforms for investigating neuro-organoids. Furthermore, the paper will assess current limitations in microfluidic design that must be addressed for realizing the full potential of brain-on-a-chip devices.

Author(s):  
Yunus Alapan ◽  
Muhammad Noman Hasan ◽  
Richang Shen ◽  
Umut A. Gurkan

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.


2003 ◽  
Vol 773 ◽  
Author(s):  
Myung-Il Park ◽  
Jonging Hong ◽  
Dae Sung Yoon ◽  
Chong-Ook Park ◽  
Geunbae Im

AbstractThe large optical detection systems that are typically utilized at present may not be able to reach their full potential as portable analysis tools. Accurate, early, and fast diagnosis for many diseases requires the direct detection of biomolecules such as DNA, proteins, and cells. In this research, a glass microchip with integrated microelectrodes has been fabricated, and the performance of electrochemical impedance detection was investigated for the biomolecules. We have used label-free λ-DNA as a sample biomolecule. By changing the distance between microelectrodes, the significant difference between DW and the TE buffer solution is obtained from the impedance-frequency measurements. In addition, the comparison for the impedance magnitude of DW, the TE buffer, and λ-DNA at the same distance was analyzed.


2021 ◽  
Vol 11 (8) ◽  
pp. 3404
Author(s):  
Majid Hejazian ◽  
Eugeniu Balaur ◽  
Brian Abbey

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Kazuki Yamamoto ◽  
Nao Yamaoka ◽  
Yu Imaizumi ◽  
Takunori Nagashima ◽  
Taiki Furutani ◽  
...  

A three-dimensional human neuromuscular tissue model that mimics the physically separated structures of motor neurons and skeletal muscle fibers is presented.


ACS Omega ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 3164-3172
Author(s):  
Zhujing Hao ◽  
Haichen Lv ◽  
Ruopeng Tan ◽  
Xiaolei Yang ◽  
Yang Liu ◽  
...  

2021 ◽  
Vol 143 (10) ◽  
Author(s):  
Ketki M. Lichade ◽  
Yayue Pan

Abstract This study successfully integrates acoustic patterning with the Two-Photon Polymerization (TPP) process for printing nanoparticle–polymer composite microstructures with spatially varied nanoparticle compositions. Currently, the TPP process is gaining increasing attention within the engineering community for the direct manufacturing of complex three-dimensional (3D) microstructures. Yet the full potential of TPP manufactured microstructures is limited by the materials used. This study aims to create and demonstrate a novel acoustic field-assisted TPP (A-TPP) process, which can instantaneously pattern and assemble nanoparticles in a liquid droplet, and fabricate anisotropic nanoparticle–polymer composites with spatially controlled particle–polymer material compositions. It was found that the biggest challenge in integrating acoustic particle patterning with the TPP process is that nanoparticles move upon laser irradiation due to the photothermal effect, and hence, the acoustic assembly is distorted during the photopolymerization process. To cure acoustic assembly of nanoparticles in the resin through TPP with the desired nanoparticle patterns, the laser power needs to be carefully tuned so that it is adequate for curing while low enough to prevent the photothermal effect. To address this challenge, this study investigated the threshold laser power for polymerization of TPP resin (Pthr) and photothermal instability of the nanoparticle (Pthp). Patterned nanoparticle–polymer composite microstructures were fabricated using the novel A-TPP process. Experimental results validated the feasibility of the developed acoustic field-assisted TPP process on printing anisotropic composites with spatially controlled material compositions.


Micromachines ◽  
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 ◽  
...  

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.


Sensors ◽  
2021 ◽  
Vol 21 (22) ◽  
pp. 7493
Author(s):  
Krystian L. Wlodarczyk ◽  
William N. MacPherson ◽  
Duncan P. Hand ◽  
M. Mercedes Maroto-Valer

In situ measurements are highly desirable in many microfluidic applications because they enable real-time, local monitoring of physical and chemical parameters, providing valuable insight into microscopic events and processes that occur in microfluidic devices. Unfortunately, the manufacturing of microfluidic devices with integrated sensors can be time-consuming, expensive, and “know-how” demanding. In this article, we describe an easy-to-implement method developed to integrate various “off-the-shelf” fiber optic sensors within microfluidic devices. To demonstrate this, we used commercial pH and pressure sensors (“pH SensorPlugs” and “FOP-MIV”, respectively), which were “reversibly” attached to a glass microfluidic device using custom 3D-printed connectors. The microfluidic device, which serves here as a demonstrator, incorporates a uniform porous structure and was manufactured using a picosecond pulsed laser. The sensors were attached to the inlet and outlet channels of the microfluidic pattern to perform simple experiments, the aim of which was to evaluate the performance of both the connectors and the sensors in a practical microfluidic environment. The bespoke connectors ensured robust and watertight connection, allowing the sensors to be safely disconnected if necessary, without damaging the microfluidic device. The pH SensorPlugs were tested with a pH 7.01 buffer solution. They measured the correct pH values with an accuracy of ±0.05 pH once sufficient contact between the injected fluid and the measuring element (optode) was established. In turn, the FOP-MIV sensors were used to measure local pressure in the inlet and outlet channels during injection and the steady flow of deionized water at different rates. These sensors were calibrated up to 140 mbar and provided pressure measurements with an uncertainty that was less than ±1.5 mbar. Readouts at a rate of 4 Hz allowed us to observe dynamic pressure changes in the device during the displacement of air by water. In the case of steady flow of water, the pressure difference between the two measuring points increased linearly with increasing flow rate, complying with Darcy’s law for incompressible fluids. These data can be used to determine the permeability of the porous structure within the device.


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