Organ-on-a-chip: recent breakthroughs and future prospects

Abstract

BackgroundMicrofluidics is a science and technology that precisely manipulates and processes microscale fluids. It is commonly used to precisely control microfluidic (10 −9 to 10 −18 L) fluids using channels that range in size from tens to hundreds of microns and is known as a "lab-on-a-chip" [1][2][3][4]. The microchannel is small, but has a large surface area and high mass transfer, favoring its use in microfluidic technology applications including low regent usage, controllable volumes, fast mixing speeds, rapid responses, and precision control of physical and chemical properties [1,5,6]. Microfluidics integrate sample preparation, reactions, separation, detection, and basic operating units such as cell culture, sorting and cell lysis [7]. For these reasons, interest in OOAC has intensified [8]. OOAC combines a range of chemical, biological and material science disciplines [9] and was selected as one of the "Top Ten Emerging Technologies" in the World Economic Forum [10].OOAC is a biomimetic system that can mimic the environment of a physiological organ, with the ability to regulate key parameters including AbstractThe organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

Application of In Vitro Metabolism Activation in High-Throughput Screening

“…OOAC combines cell biology, bioengineering, and biomaterial technology allowing us to mimic a specific organ. This technique will allow for greater prediction of the effects of metabolites to each individual organ [130]. Although OOAC can be utilized in an HTS format, there are some challenges to consider, such as automation in dispensing, washing, and monitoring [131].…”

Multiplexed blood–brain barrier organ-on-chip

“…11 Recently, the urgent need for a less expensive and physiologically relevant model has led to the development of organ-on-chip (OOC) systems based on microfluidic techniques. 12,13 OOC models resemble some components of the complex in vivo environment with an ECM, cell-cell interactions, and vasculature-like perfusion while requiring a minimal quantity of fluid and sample consumption due to micrometer size of the channels. 14 It is possible to implement miniaturized sensors into the devices enabling real-time monitoring of tissue development and function.…”

Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies

“…Many times, the real usefulness of these models, as is the case of BBB/brain-on-a-chip, is translated in the fact that they allow for simultaneous monitoring and recording of biological responses to a number of stimuli [123]. However, on-chip sample collecting is not very practical nor feasible, since it can interfere with its operation, risking changes in the concentration of biomarkers/metabolites and potentially generating data that cannot be correlated with what happens in vivo [124]. The integration of more sensible and cost-effective sensors that perform the analysis independently in the micro-space of the chip is therefore required [122,123].…”

“…Another relevant point is the source of the biological tissue [124]. Induced pluripotent stem cells (iPSC) are a very attractive choice for cell culture in microfluidic systems, given their virtually unlimited ability to self-renewal and differentiate into multiple somatic lineages [7,41].…”

“…Indeed, extensive work has already been conducted in regard to the incorporation of stem cells in BBB/brain-on-a-chip for engineering neural networks and brain tissues [41]. iPSC circumvent the ethical controversies associated with traditional embryonic stem cells and maintain several BBB physiological attributes, including the presence of TJ proteins and similar molecular permeability coefficients [7,124]. Furthermore, they can be obtained from individual patients, which will drive forth not only the development of patient-specific brain disease models, but also of personalized drug screening.…”