Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering and microfabrication, OoCs have gained interest as a next-generation experimental platform to investigate human pathophysiology and the effect of therapeutics in the body. There are as many examples of OoCs as there are applications, making it difficult for new researchers to understand what makes one OoC more suited to an application than another. This Primer is intended to give an introduction to the aspects of OoC that need to be considered when developing an application-specific OoC. The Primer covers guiding principles and considerations to design, fabricate and operate an OoC, as well as subsequent assaying techniques to extract biological information from OoC devices. Alongside this is a discussion of current and future applications of OoC technology, to inform design and operational decisions during the implementation of OoC systems. Organs-on-chips are microfluidic systems containing miniature tissues with the aim of mimicking human physiology for a range of biomedical and therapeutic applications. Leung, de Haan et al. report practical tips to inform design and operational decisions during the implementation of organ-on-a-chip systems. 

A guide to the organ-on-a-chip

The native tissues are complex structures consisting of different cell types, extracellular matrix materials, and biomolecules. Traditional tissue engineering strategies have not been able to fully reproduce biomimetic and heterogeneous tissue constructs because of the lack of appropriate biomaterials and technologies. However, recently developed three-dimensional bioprinting techniques can be leveraged to produce biomimetic and complex tissue structures. To achieve this, multicomponent bioinks composed of multiple biomaterials (natural, synthetic, or hybrid natural-synthetic biomaterials), different types of cells, and soluble factors have been developed. In addition, advanced bioprinting technologies have enabled us to print multimaterial bioinks with spatial and microscale resolution in a rapid and continuous manner, aiming to reproduce the complex architecture of the native tissues. This review highlights important advances in heterogeneous bioinks and bioprinting technologies to fabricate biomimetic tissue constructs. Opportunities and challenges to further accelerate this research area are also described.

Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs.

Microfluidic devices currently play an important role in many biological, chemical, and engineering applications, and there are many ways to fabricate the necessary channel and feature dimensions In this review, we provide an overview of microfabrication techniques that are relevant to both research and commercial use A special emphasis on both the most practical and the recently developed methods for microfluidic device fabrication is applied, and it leads us to specifically address laminate, molding, 3D printing, and high resolution nanofabrication techniques The methods are compared for their relative costs and benefits, with special attention paid to the commercialization prospects of the various technologies

/pdf/a-review-of-current-methods-in-microfluidic-device-2i6ku5y966.pdf

A Review of Current Methods in Microfluidic Device Fabrication and Future Commercialization Prospects

https://www.nature.com/articles/s43586-022-00118-6.pdf

3D printing is becoming increasingly prevalent in modern chemistry laboratories. This technology provides chemists with the ability to design, prototype and print functional devices that integrate catalytic and/or analytical functionalities and even to print common laboratory hardware and teaching aids. Although access to 3D printers has increased considerably, some design principles and material considerations need to be weighed before employing such technology in chemistry laboratories. In addition, a certain level of expertise needs to be acquired in order to use computer-aided design, printing software and the specialist hardware associated with higher-end instrumentation. Nonetheless, the recent progress in this field is encouraging, with these printing technologies offering many advantages over traditional production methods. This Review highlights some of the notable advances in this growing area over the past decade. 3D printing is becoming a mainstream technology with considerable increase in access to affordable desktop printers. However, specific design principles and material considerations need to be weighed when printing functional devices that integrate catalytic and/or analytical functionalities, as well as when printing common laboratory hardware.

3D printing for chemical, pharmaceutical and biological applications

The advent of 3D printing technologies promises to make microfluidic organ-on-chip technologies more accessible for the biological research community. To date, hydrogel-encapsulated cells have been successfully incorporated into 3D printed microfluidic devices. However, there is currently no 3D printed microfluidic device that can support multicellular spheroid culture, which facilitates extensive cell-cell contacts important for recapitulating many multicellular functional biological structures. Here, we report a first instance of fabricating a 3D printed microfluidic cell culture device capable of directly immobilizing and maintaining the viability and functionality of 3D multicellular spheroids. We evaluated the feasibility of two common 3D printing technologies i.e. stereolithography (SLA) and PolyJet printing, and found that SLA could prototype a device comprising of cell immobilizing micro-structures that were housed within a microfluidic network with higher fidelity. We have also implemented a pump-free perfusion system, relying on gravity-driven flow to perform medium perfusion in order to reduce the complexity and footprint of the device setup, thereby improving its adaptability into a standard biological laboratory. Finally, we demonstrated the biological performance of the 3D printed device by performing pump-free perfusion cultures of patient-derived parental and metastatic oral squamous cell carcinoma tumor and liver cell (HepG2) spheroids with good cell viability and functionality. This paper presents a proof-of-concept in simplifying and integrating the prototyping and operation of a microfluidic spheroid culture device, which will facilitate its applications in various drug efficacy, metabolism and toxicity studies.

https://iopscience.iop.org/article/10.1088/1758-5090/aa8858/pdf

A 3D printed microfluidic perfusion device for multicellular spheroid cultures.

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A 3D printed microfluidic perfusion device for multicellular spheroid cultures.