A Fast Alternative to Soft Lithography for the Fabrication of Organ‐on‐a‐Chip Elastomeric‐Based Devices and Microactuators

Abstract

Organ-on-a-chip technology promises to revolutionize how pre-clinical human trials are conducted. Engineering an in vitro environment that mimics the functionality and architecture of human physiology is essential toward building better platforms for drug development and personalized medicine. However, the complex nature of these devices requires specialized, time consuming, and expensive fabrication methodologies. Alternatives that reduce design-to-prototype time are needed, in order to fulfill the potential of these devices. Here, a streamlined approach is proposed for the fabrication of organ-on-a-chip devices with incorporated microactuators, by using an adaptation of xurography. This method can generate multilayered, membrane-integrated biochips in a matter of hours, using low-cost benchtop equipment. These devices are capable of withstanding considerable pressure without delamination. Furthermore, this method is suitable for the integration of flexible membranes, required for organ-on-a-chip applications, such as mechanical actuation or the establishment of biological barrier function. The devices are compatible with cell culture applications and present no cytotoxic effects or observable alterations on cellular homeostasis. This fabrication method can rapidly generate organ-on-a-chip prototypes for a fraction of cost and time, in comparison to conventional soft lithography, constituting an interesting alternative to the current fabrication methods.

3D bioprinted organ‐on‐chips

“…In particular, lithographic techniques need to be carried out through several lithographic processes and masks. [29,96,98] This leads to experiments that are time consuming and expensive. In addition, the traditional methods require a secondary organization for the cell seeding process, which oftentimes drives up the overall cost, as well as poor selectivity of different cell types.…”

Digital manufacturing for accelerating organ-on-a-chip dissemination and electrochemical biosensing integration

“…As mould fabrication and PDMS casting are eliminated they can directly construct devices in minutes while mould fabrication can take up to two days for only double layered chips. 26 Furthermore, DM technologies could be employed in either direct writing mode to pattern fully functional devices directly on the substrate, or to create micromoulds for polymer casting in a similar way to soft lithography and injection moulding. 27 In this way, those groups experienced in soft lithography can incorporate all the advantages of DM direct writing modes while maintaining the option to make alternative micromoulds for PDMS casting (Fig.…”

“…More recently, xurography has been demonstrated to be a suitable approach to micropattern pre-cured PDMS foil of different thicknesses (250 μm, 500 μm, 750 μm) and create multilayered devices that encompass fluidic and pneumatic control layers. 41 The applicability of these devices has been demonstrated by cross-talking studies between synovial and chondral organoids for the modelling of arthritic diseases 42 and dermal fibroblast migration for wound healing. 43 Although PDMS-based devices have demonstrated their potential, PDMS possesses several shortcomings as a material (e.g., small molecule adsorption, hydrophobic recovery, water evaporation, and uncross linked oligomers) which makes it imperative to find alternative materials for OoC construction.…”

Cancer-on-chip technology: current applications in major cancer types, challenges and future prospects

“…One recent attempt to address this problem was reported by Ferreira et al 132 . They described a rapid OOC manufacturing method based on xurography 132 . Xurography can be defined as the process in which the designed shape of each microfluidic channel is cut in a pre-cured thin PDMS layer.…”