Rapid prototyping of whole-thermoplastic microfluidics with built-in microvalves using laser ablation and thermal fusion bonding

Shaegh, Seyed Ali Mousavi; Pourmand, Adel; Nabavinia, Mahboubeh; Avcı, Hüseyin; Tamayol, Ali; Mostafalu, Pooria; Ghavifekr, Habib Badri; Aghdam, Esmaeil Najafi; Dokmeci, Mehmet R.; Khademhosseini, Ali; Zhang, Yu Shrike

doi:10.1016/j.snb.2017.07.138

Cited by 114 publications

(85 citation statements)

References 54 publications

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“…13,14 Importantly, in multiple-OoC systems, two or more bioreactors, which might require different levels of oxygen tension, are interconnected. 16 The easiest way to control oxygen tension in a bioreactor is through the modulation of the flow rate. 15 Delivery of sufficient oxygen to microfluidic bioreactors mainly occur through (i) oxygen diffusion from the permeable walls of the fluidic system or (ii) an oxygenator that is mainly made from a thin oxygen-permeable membrane implemented in the wall of the fluidic system or the bioreactor.…”

Section: Introductionmentioning

confidence: 99%

“…For such devices, the oxygenation is provided through an oxygen-permeable membrane that can be made from high-oxygen-permeable materials such as PDMS or TPU. 16 The easiest way to control oxygen tension in a bioreactor is through the modulation of the flow rate. However, changing the flow rate could affect the flow-induced shear stresses experienced by the cultured cells, pressure drop, and the transport characteristics of biomolecular species that consequently limits the practical domain of the flow rate.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of oxygen transport in microfluidic bioreactors for cell culture and organ‐on‐chip applications

Kheibary

Esfahani

Shaegh

2020

Engineering Reports

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In the recent decade, development of microfluidic bioreactors and organ-onchip platforms for drug screening and disease modeling has been rising significantly. Prediction of oxygen level within the microfluidic bioreactors to create physiologically relevant oxygen tension for realistic cellular behavior is of critical importance. This article presented an analytical method to calculate oxygen tension in microchannel parallel plate bioreactors. Two-dimensional convection-diffusion equation was solved analytically with considering diffusion in two directions. Cellular oxygen consumption was assumed to follow Michaelis-Menten kinetics. Effects of oxygenator design, gas permeability of the microfluidic channels, as well as flow rate and cell density on the oxygen distribution within the bioreactor were examined. In addition, a mathematical model was developed to predict oxygen tension in a fluidic circuit containing two interconnected bioreactors with and without recirculation of the media for the culture of hepatocytes and cardiomyocytes. The oxygenators were used to maintain normoxia in the bioreactors independently. The model allowed for the prediction and independent modulation of oxygen tension in the two bioreactors through changing the length of the oxygenators. In overall, the obtained results provide critical insights required for the design and operation of microfluidic bioreactors with desired levels of oxygen tension.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of oxygen transport in microfluidic bioreactors for cell culture and organ‐on‐chip applications

Kheibary

Esfahani

Shaegh

2020

Engineering Reports

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“…A number of reviews has described thermoplastic microfabrication methods [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ], and recent work [ 14 ] discussed the transition from glass and silicon to thermoplastics, while discussing the available fabrication methods for these materials, methods that are often far faster and less expensive. As recently surveyed [ 15 , 16 ], a wide range of demonstrations has developed the use of thermoplastic substrates especially (e.g., [ 17 ] and the references within) in integrations of PDMS with thermoplastics such as poly(methyl methacrylate) (PMMA) and using methods such as plasma activated bonding and hot embossing. Very low cost fabrication methods have been emphasised for such membrane-based chips, for example the recent work [ 18 ] that thermally bonded layers of a variety of polymers to form microvalves.…”

Section: Introductionmentioning

confidence: 99%

“…The use of CO

lasers was presented as an ideal way of enabling rapid prototyping of PMMA [ 33 ]. CO

laser-based microfabrication with PMMA has been used in a wide range of applications, from droplet formation [ 34 ], to cell culture [ 15 ] and electrophoretic devices [ 35 ]. Rapid prototyping methods for microfluidics have been compared [ 36 ], but laser ablation appears to be a preferred method, with the CO

laser-based processing of PMMA being perhaps the most commonly-used approach.…”

Section: Introductionmentioning

confidence: 99%

“…Recent reports [ 15 , 16 ] demonstrated a very effective way of rapidly fabricating diaphragm-based PMMA and thermoplastic polyurethane (TPU) microfluidics. Rather than use cleanroom-based photolithography in a complex process (typically several days or more), these recent reports used a CO

laser to pattern thermoplastics, forming arbitrarily complex microfluidics within about a day and without cleanroom equipment.…”

Section: Introductionmentioning

confidence: 99%

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CO2 Laser-Based Rapid Prototyping of Micropumps

Strike

Ghofrani²,

Backhouse

2018

Micromachines

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The fabrication of microdevices for fluidic control often requires the use of flexible diaphragms in a way that requires cleanroom equipment and compromises performance. We use a CO2 laser to perform the standard ablative techniques of cutting and engraving materials, but we also apply a method that we call laser placement. This allows us to fabricate precisely-positioned and precisely-sized, isolated diaphragms. This in turn enables the rapid prototyping of integrated multilayer microfluidic devices to form complex structures without the need for manual positioning or cleanroom equipment. The fabrication process is also remarkably rapid and capable of being scaled to manufacturing levels of production. We explore the use of these devices to construct a compact system of peristaltic pumps that can form water in oil droplets without the use of the non-pulsatile pumping systems typically required. Many devices can be fabricated at a time on a sheet by sheet basis with a fabrication process that, to our knowledge, is the fastest reported to date for devices of this type (requiring only 3 h). Moreover, this system is unusually compact and self-contained.

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Tunable and Reversible Gelatin‐Based Bonding for Microfluidic Cell Culture

et al. 2019

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Microfluidic cell culture is widely used to develop biochips and biosensors, culturing and experimenting with cells at the microscale. However, only a very small subset of the existing polymers is currently used in microfluidics. This is mostly due to limitations in reversibility and gas-permeability on the sealant. Hence, the development of a novel bonding technique can enable new applications and uses of plastics in microfluidic cell culture, complementing the omnipresent polydimethylsiloxane (PDMS) for critical applications where harder or non-porous materials are required. The present paper describes a reversible gelatin-based room-temperature method for bonding separate substrates, which enables the sealing of commonly used materials in microfluidics such as thermoplastics, but also elastomers and photopolymers. For most materials, the bonding chip resisted to at least 0.1 MPa. To show the versatility of the described method we bonded microchannels of different sizes, up to 200 μm, and round microstructures.The applicability to cell culture was investigated by culturing colorectal cancer HT-29 cells within the chip. Finally, the cells viability was analyzed by in situ live/dead fluorescence staining. Advantageously, the proposed bonding process is reversible and make possible to tune the permeability of the gelatin layer integrated on chip. This room-temperature bonding method is highly efficient for cell culture in plastic chips, potentially opening new routes for the development of innovative BioMEMS devices.

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Rapid prototyping of whole-thermoplastic microfluidics with built-in microvalves using laser ablation and thermal fusion bonding

Cited by 114 publications

References 54 publications

Analysis of oxygen transport in microfluidic bioreactors for cell culture and organ‐on‐chip applications

Analysis of oxygen transport in microfluidic bioreactors for cell culture and organ‐on‐chip applications

CO2 Laser-Based Rapid Prototyping of Micropumps

Tunable and Reversible Gelatin‐Based Bonding for Microfluidic Cell Culture

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