Fabricating smooth PDMS microfluidic channels from low-resolution 3D printed molds using an omniphobic lubricant-infused coating

Villegas, Martin; Cetinic, Zachary; Shakeri, Amid; Didar, Tohid F.

doi:10.1016/j.aca.2017.11.063

Cited by 100 publications

(68 citation statements)

References 25 publications

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“…In recent years, in the field of biomedical research, microfluidics has emerged as a promising alternative due to its high throughput, automation capabilities, and low fabrication and operation costs [111]. However, current microfluidic devices have relied on multi-step lithographic processes, which are time-consuming and complicated.…”

Section: Microfluidics Via 3d Printingmentioning

confidence: 99%

In vitro modeling of the neurovascular unit: advances in the field

Bhalerao

Sivandzade

Archie

et al. 2020

Fluids Barriers CNS

118

103

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The blood-brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the other hand, the BBB is also a major hindering obstacle for the delivery of effective therapies to treat disorders of the Central Nervous System (CNS). Over time, various model systems have been established to simulate the complexities of the BBB. The development of realistic in vitro BBB models that accurately mimic the physiological characteristics of the brain microcapillaries in situ is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the Neurovascular Unit (NVU) would provide an invaluable tool that would aid in dissecting out the pathological factors, mechanisms of action, and corresponding targets prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many fundamental changes in the last few years with the introduction of novel tools and methods to improve existing models and enable new ones. The development of CNS organoids, organ-on-chip, spheroids, 3D printed microfluidics, and other innovative technologies have the potential to advance the field of BBB and NVU modeling. Therefore, in this review, summarize the advances and progress in the design and application of functional in vitro BBB platforms with a focus on rapidly advancing technologies.The BBB consists of highly specialized vascular endothelial cells (EC) lining the brain microvessels in juxtaposition with closely associated pericytes [1], extracellular matrix components, and astrocytic end-feet processes [2]. Along with other cells such as neurons and microglia, this cellular milieu modulates the BBB properties, supports its viability and functions [3]. At the brain microvascular level, the BBB functions as a highly dynamic and active interface between the systemic circulation and the CNS. The BBB maintains a stable brain environment to protect the CNS from unsolicited cells, bacteria, viruses, and potentially harmful substances (either endogenous or exogenous) apart from protecting against systemic fluctuations. The BBB also regulates the transport of essential molecules and nutrients necessary to maintain the optimal CNS environment and support neuronal activities [4]. The BBB responds to many physiological and pathological cues, including rheological changes [5], inflammatory stimuli, oxidative stress [6], diabetes, and hypercholesterolemia [7-10], acute brain injury [3], etc. The intrinsically unique and utmost complex functional interaction between the BBB endothelium and the surrounding cellular milieu (including astrocytes, pericytes, neurons, microglia, myocytes as well as specialized cellular compartments such as endothelial glycocalyx [11,12] has been termed "neurovascular unit (NVU)" [2,13]. In addition, the basement membrane, which exerts essential functions in cellular support and signal transduction,

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Section: Microfluidics Via 3d Printingmentioning

confidence: 99%

In vitro modeling of the neurovascular unit: advances in the field

Bhalerao

Sivandzade

Archie

et al. 2020

Fluids Barriers CNS

118

103

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“…Currently, 3D printed molds are increasingly used to cast PDMS devices as an alternative to SU-8 molds 10,17 . While this strategy removes the direct contact of 3D printed resins with biological materials, questions remain on the fate of leachates from the mold and their potential transfer into the PDMS matrix during curing to eventually end up in the cell/tissue culture compartment.…”

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confidence: 99%

3D printed mold leachates in PDMS microfluidic devices

Ferraz

Nagashima

Venzac

et al. 2020

Sci Rep

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The introduction of poly(dimethylsiloxane) (PDMS) and soft lithography in the 90's has revolutionized the field of microfluidics by almost eliminating the need for a clean-room environment for device fabrication. More recently, 3D printing has been introduced to fabricate molds for soft lithography, the only step for which a clean-room environment is still often necessary, to further support the rapid prototyping of PDMS microfluidic devices. However, toxicity of most of the commercial 3D printing resins has been established, and little is known regarding the potential for 3D printed molds to leak components into the PDMS that would, in turn, hamper cells and/or tissues cultured in the devices. In the present study, we investigated if 3D printed molds produced by stereolithography can leach components into PDMS, and compared 3D printed molds to their more conventional SU-8 counterparts. Different leachates were detected in aqueous solutions incubated in the resulting PDMS devices prepared from widely used PDMS pre-polymer:curing agent ratios (10:1, 15:1 and 20:1), and these leachates were identified as originating from resins and catalyst substances. Next, we explored the possibility to culture cells and tissues in these PDMS devices produced from 3D printed molds and after proper device washing and conditioning. Importantly, we demonstrated that the resulting PDMS devices supported physiological cultures of HeLa cells and ovarian tissues in vitro, with superior outcomes than static conventional cultures. Organ-on-a-chip models, by providing an in vivo-like environment, show great potential to advance our understanding of tissue development, physiology, and pathology 1. However, the spread of these highly promising platforms out of specialized microfluidic laboratories is hindered by essential technical challenges. The fabrication of these devices requires having access to dedicated infrastructure such as clean-room facilities with specialized equipment, which is absent in most biological laboratories 1. Novel fabrication processes have been developed to support the rapid prototyping of microfluidic devices, including soft-lithography using PDMS (polydimethylsiloxane) 2,3. PDMS is a transparent, flexible, gas-permeable, fairly inexpensive and rapidly prototyped elastomeric material, which has now become ubiquitous in the field of microfluidics 2,3. PDMS devices are commonly fabricated using molds based on SU-8 (Microchem Corp.), which is a negative epoxy-based photoresist 4. However, the fabrication of SU-8 molds uses lithography and includes multiple steps, it altogether takes several hours per fabrication cycle, and still requires dedicated training and access to a clean-room facility 5,6. As a new revolution in the field of microfluidics, 3D printing has more recently been introduced 7. Initially the use of 3D printing was limited by the price of the printers, their low resolution, the roughness of the 3D printed structures, and the toxicity of the resins 8-10. Photopolymerization-based techniques, such as dig...

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“…More research in the field of surface blocking is also required to be done with regard to surface blocking strategy in order to better prevent all nonspecific binding, thereby enhancing the efficacy of the final device. Fluorosilanization of the microchannels and use of surface wrinkling as well as lubricant‐infused technologies could be some potential alternative ways of blocking rather than the conventional blocking agents such as PEG or BSA.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Shakeri

Jarad

Leung

et al. 2019

Adv Materials Inter

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Biofunctionalization of microchannels is of great concern in the fabrication of microfluidic devices. Different substrates such as glass slides, papers, polymers, and beads require different biofunctionalization approaches granting the utilization of microfluidics in several biomedical applications. Covalent immobilization of biomolecules inside the microchannels is achieved by chemical modification of the surface such as silanization or introducing different coupling agents. Although creating biointerfaces that are covalently bonded to the microchannel surface necessitates multiple steps of surface modification and incubation times, it bestows a robust biointerface capable of withstanding high shear stresses and harsh conditions without dissipating the biofunctionality. Regarding the applications that do not require robustness and long‐term stability, noncovalent attachment of biomolecules such as van der Waals and hydrophobic interactions are adequate to successfully create a functional biointerface. This review summarizes the various biofunctionalization approaches used in the most common microfluidic substrates: glass and paper. In addition, several biofunctionalization examples are proposed and described in detail along with their associated applications.

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Fabricating smooth PDMS microfluidic channels from low-resolution 3D printed molds using an omniphobic lubricant-infused coating

Cited by 100 publications

References 25 publications

In vitro modeling of the neurovascular unit: advances in the field

In vitro modeling of the neurovascular unit: advances in the field

3D printed mold leachates in PDMS microfluidic devices

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

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