Imaging microphysiological systems: a review

Peel, Samantha; Jackman, Mark

doi:10.1152/ajpcell.00186.2020

Cited by 18 publications

(11 citation statements)

References 110 publications

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“…MPS are increasingly being used to model vascular systems (22,23), and they have facilitated the exploration of mechanisms of human disease because of their ability to replicate vascular physiology with human cells. The attention placed on essential physiology, in conjunction with the ability to rapidly evaluate acute vascular barrier dysfunction in a high-throughput format, enables MPS to serve as platforms for discovering future pharmaceutical interventions (25) with high physiological relevance.…”

Section: Discussionmentioning

confidence: 99%

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A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic

et al. 2023

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High-content imaging techniques in conjunction with in vitro microphysiological systems (MPS) allow for novel explorations of physiological phenomena with a high degree of translational relevance due to the usage of human cell lines. MPS featuring ultrathin and nanoporous silicon nitride membranes (µSiM) have been utilized in the past to facilitate high magnification phase contrast microscopy recordings of leukocyte trafficking events in a living mimetic of the human vascular microenvironment. Notably, the imaging plane can be set directly at the endothelial interface in a µSiM device, resulting in a high-resolution capture of an endothelial cell (EC) and leukocyte coculture reacting to different stimulatory conditions. The abundance of data generated from recording observations at this interface can be used to elucidate disease mechanisms related to vascular barrier dysfunction, such as sepsis. The appearance of leukocytes in these recordings is dynamic, changing in character, location and time. Consequently, conventional image processing techniques are incapable of extracting the spatiotemporal profiles and bulk statistics of numerous leukocytes responding to a disease state, necessitating labor-intensive manual processing, a significant limitation of this approach. Here we describe a machine learning pipeline that uses a semantic segmentation algorithm and classification script that, in combination, is capable of automated and label-free leukocyte trafficking analysis in a coculture mimetic. The developed computational toolset has demonstrable parity with manually tabulated datasets when characterizing leukocyte spatiotemporal behavior, is computationally efficient and capable of managing large imaging datasets in a semi-automated manner.

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Section: Discussionmentioning

confidence: 99%

“…Recently, the emergence of microphysiological systems (MPS) for in vitro tissue models has facilitated the exploration of vascular physiology in a living mimetic of a tissue microenvironment (22,23). Notably, there is an increasing ability to recreate microscale vascular structures (24) in these systems.…”

Section: Introductionmentioning

confidence: 99%

A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic

et al. 2023

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“…This approach accounts for technical artifacts and reduces manual effort thus allowing for higher throughput and higher quality studies. While strides have been taken in the field of imaging to improve both the microscopes and their associated image analysis software, these tools often reduce analysis to a 2-D representation, introducing an opportunity to miss spatial features of the system (Peel 2021). Some open-source image analysis tools offer 3-D analysis options, but these tools often require computational expertise and depend on multiple manual filtering steps, limiting the ability to automate analysis and perform high throughput investigations (Kriston-Vizi, 2017).…”

Section: Discussionmentioning

confidence: 99%

A novel thin plate spline methodology to model tissue surfaces and quantify tumor cell invasion in organ-on-chip models

Elton,

Strelez,

Ung

et al. 2023

Preprint

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Organ-on-chip (OOC) models can be useful tools for cancer drug discovery. Advances in OOC technology have led to the development of more complex assays, yet analysis of these systems does not always account for these advancements, resulting in technical challenges. A challenging task in the analysis of these two-channel microfluidic models is to define the boundary between the channels so objects moving within and between channels can be quantified. We propose a novel imaging-based application of a thin plate spline method – a generalized cubic spline that can be used to model coordinate transformations – to model a tissue boundary and define compartments for quantification of invaded objects, representing the early steps in cancer metastasis. To evaluate its performance, we applied our analytical approach to an adapted OOC developed by Emulate, Inc., utilizing a two-channel system with endothelial cells in the bottom channel and colorectal cancer (CRC) patient-derived organoids (PDOs) in the top channel. Initial application and visualization of this method revealed boundary variations due to microscope stage tilt and ridge and valley-like contours in the endothelial tissue surface. The method was functionalized into a reproducible analytical process and web tool – the Chip Invasion and Contour Analysis (ChICA) – to model the endothelial surface and quantify invading tumor cells across multiple chips. To illustrate applicability of the analytical method, we applied the tool to CRC organoid-chips seeded with two different endothelial cell types and measured distinct variations in endothelial surfaces and tumor cell invasion dynamics. Since ChICA utilizes only positional data output from imaging software, the method is applicable to and agnostic of the imaging tool and image analysis system used. The novel thin plate spline method developed in ChICA can account for variation introduced in OOC manufacturing or during the experimental workflow, can quickly and accurately measure tumor cell invasion, and can be used to explore biological mechanisms in drug discovery.

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“…These models can be combined with organoids or patient-derived tissue samples for personalized models and integrated with the latest imaging technologies to extract robust and quantitative information. 162 The intention with this emerging technology is to recreate specific organ functions inside the laboratory and ultimately combine them into a single body-on-a-chip. Such a device could substitute animal testing and become the next-generation platform for in vitro testing in the pharmaceutical industry, [163][164][165] and in space.…”

Section: Concluding Remarks and Future Perspectivementioning

confidence: 99%

Organ‐on‐a‐chip technologies for biomedical research and drug development: A focus on the vasculature

2023

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Current biomedical models fail to replicate the complexity of human biology.Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ-on-a-chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient-derived induced pluripotent stem cells, organon-a-chip technologies are the future of drug discovery, development, and personalized medicine. K E Y W O R D Sbiomedical, microphysiological systems, models, organ-on-a-chip, vasculatureThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Imaging microphysiological systems: a review

Cited by 18 publications

References 110 publications

A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic

A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic

A novel thin plate spline methodology to model tissue surfaces and quantify tumor cell invasion in organ-on-chip models

Organ‐on‐a‐chip technologies for biomedical research and drug development: A focus on the vasculature

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