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.

In this work, the use of fused deposition modeling (FDM) in a (bio)analytical/lab-on-a-chip research laboratory is described. First, the specifications of this 3D printing method that are important for the fabrication of (micro)devices were characterized for a benchtop FDM 3D printer. These include resolution, surface roughness, leakage, transparency, material deformation, and the possibilities for integration of other materials. Next, the autofluorescence, solvent compatibility, and biocompatibility of 12 representative FDM materials were tested and evaluated. Finally, we demonstrate the feasibility of FDM in a number of important applications. In particular, we consider the fabrication of fluidic channels, masters for polymer replication, and tools for the production of paper microfluidic devices. This work thus provides a guideline for (i) the use of FDM technology by addressing its possibilities and current limitations, (ii) material selection for FDM, based on solvent compatibility and biocompatibility, and (iii) application of FDM technology to (bio)analytical research by demonstrating a broad range of illustrative examples.

Oxygen is essential in the energy metabolism of cells, as well as being an important regulatory parameter influencing cell differentiation and function. Interest in precise oxygen control for in vitro cultures of tissues and cells continues to grow, especially with the emergence of the organ-on-a-chip and the desire to emulate in vivo conditions. This was recently discussed in this journal in a Critical Review by Brennan et al. (Lab Chip (2014). DOI: 10.1039/C4LC00853G). Microfluidics can be used to introduce flow to facilitate nutrient supply to and waste removal from in vitro culture systems. Well-defined oxygen gradients can also be established. However, cells can quickly alter the oxygen balance in their vicinity. In this Tutorial Review, we expand on the Brennan paper to focus on the implementation of oxygen analysis in these systems to achieve continuous monitoring. Both electrochemical and optical approaches for the integration of oxygen monitoring in microfluidic tissue and cell culture systems will be discussed. Differences in oxygen requirements from one organ to the next are a challenging problem, as oxygen delivery is limited by its uptake into medium. Hence, we discuss the factors determining oxygen concentrations in solutions and consider the possible use of artificial oxygen carriers to increase dissolved oxygen concentrations. The selection of device material for applications requiring precise oxygen control is discussed in detail, focusing on oxygen permeability. Lastly, a variety of devices is presented, showing the diversity of approaches that can be employed to control and monitor oxygen concentrations in in vitro experiments.

This paper focuses on one of the most commonly encountered materials in our society, namely paper. Paper is an inherently complex material, yet its use provides for chemical analysis approaches that are elegant in their simplicity of execution. In the first half of the previous century, paper in scientific research was used mainly for filtration and chromatographic separation. While its use decreased with the rise of modern elution chromatography, paper remains a versatile substrate for low-cost analytical tests. Recently, we have seen renewed interest to work with paper in (bio)analytical science, a result of the growing demand for inexpensive, portable analysis. Dried blood spotting, paper microfluidics, and paper spray ionization are areas in which paper is (re)establishing itself as an important material. These research areas all exploit several properties of paper, including stable sample storage, passive fluid movement and manipulation, chromatographic separation/extraction, modifiable surface and/or volume, easily altered shape, easy transport, and low cost. We propose that the real, and to date underexploited, potential of paper lies in utilizing its combined characteristics to add new dimensions to paper-based (bio)chemical analysis, expanding its applicability. This article provides the reader with a short historical perspective on the scientific use of paper and the developments that led to the establishment of the aforementioned research areas. We review important characteristics of paper and place them in a scientific context in this descriptive, yet critical, assessment of the achieved and the achievable in paper-based analysis. The ultimate goal is the exploration of integrative approaches at the interface between the different fields in which paper is or can be used.

In vitro digestions are essential for determining the bioavailability of compounds, such as nutrients. We have developed a cell-free, miniaturized enzymatic digestive system, employing three micromixers connected in series to mimic the digestive functions of the mouth, stomach and small intestine. This system continuously processes samples, e.g. containing nutrients, to provide a constant flow of digested materials which may be presented to a subsequent gut-on-a-chip absorption module, containing living human intestinal cells. Our system incorporates three-compartment enzymatic digestion, one of the key functions of the gastrointestinal tract. In each of these compartments, we modify the chemical environment, including pH, buffer, and mineral composition, to closely mimic the local physiological environment and create optimal conditions for digestive processes to take place. It will therefore provide an excellent addition to existing gut-on-a-chip systems, providing the next step in determining the bio-availability of orally administered compounds in a fast and continuous-flow ex vivo system. In this paper, we demonstrate enzymatic digestion in each separate compartment using compounds, starch and casein, as model nutrients. The use of transparent, microfluidic micromixers based on chaotic advection, which can be probed directly with a microscope, enabled enzyme kinetics to be monitored from the very start of a reaction. Furthermore, we have digested lactoferrin in our system, demonstrating complete digestion of this milk protein in much shorter times than achievable with standard in vitro digestions using batch reactors.