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Rapid Prototyping of Organ-on-a-Chip Devices Using Maskless Photolithography.

ABSTRACT: Organ-on-a-chip (OoC) and microfluidic devices are conventionally produced using microfabrication procedures that require cleanrooms, silicon wafers, and photomasks. The prototyping stage often requires multiple iterations of design steps. A simplified prototyping process could therefore offer major advantages. Here, we describe a rapid and cleanroom-free microfabrication method using maskless photolithography. The approach utilizes a commercial digital micromirror device (DMD)-based setup using 375 nm UV light for backside exposure of an epoxy-based negative photoresist (SU-8) on glass coverslips. We show that microstructures of various geometries and dimensions, microgrooves, and microchannels of different heights can be fabricated. New SU-8 molds and soft lithography-based polydimethylsiloxane (PDMS) chips can thus be produced within hours. We further show that backside UV exposure and grayscale photolithography allow structures of different heights or structures with height gradients to be developed using a single-step fabrication process. Using this approach: (1) digital photomasks can be designed, projected, and quickly adjusted if needed; and (2) SU-8 molds can be fabricated without cleanroom availability, which in turn (3) reduces microfabrication time and costs and (4) expedites prototyping of new OoC devices.

SUBMITTER: Kasi DG

PROVIDER: S-EPMC8778126 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In the advent of affordable photo- and soft-lithography using polydimethylsiloxane (PDMS), low cost multi-step microfabrication methods have become available to a broad scientific community today. Although these methods are frequently applied for microfluidic prototype production in academic and industrial settings, fast design iterations and rapid prototyping within a few minutes with a high degree of flexibility are nearly impossible. To reduce microfluidic concept-to-chip time and costs, a number of alternative rapid prototyping techniques have recently been introduced including CNC micromachining, 3D printing and plotting out of numeric CAD designs as well as micro-structuring of thin PDMS sheets and pressure sensitive adhesives. Although micro-structuring of pressure sensitive adhesives promises high design flexibility, rapid fabrication and simple biochip assembly, most adhesives are toxic for living biological systems. Since an appropriate bio-interface and proper biology-material interaction is key for any cell chip and organ-on-a-chip system, only a limited number of medical-grade materials are available for microfluidic prototyping. In this study, we have characterized four functional biomedical-grade pressure sensitive adhesives for rapid prototyping (e.g. less than 1 hour) applications including structuring precision, physical and optical properties as well as biocompatibilities. While similar biocompatibility was found for all four adhesives, significant differences in cutting behavior, bonding strength to glass and polymers as well as gas permeability was observed. Practical applications included stability testing of multilayered, membrane-integrated organ-on-a-chip devices under standard cell culture conditions (e.g. 2-3 weeks at 37 °C and 100% humidity) and a shear-impact up to 5 dynes/cm2. Additionally, time- and shear-dependent uptake of non-toxic fluorescently labelled nanoparticles on human endothelial cells are demonstrated using micro-structured adhesive-bonded devices. Our results show that (a) both simple and complex microdevices can be designed, fabricated and tested in less than 1 hour, (b) these microdevices are stable for weeks even under physiological shear force conditions and (c) can be used to maintain cell monolayers as well as 3D cell culture systems.

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Rapid Prototyping of Organ-on-a-Chip Devices Using Maskless Photolithography.

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