Microphysiological systems and low-cost microfluidic platform with analytics

Abstract

A multiorgan, functional, human in vitro assay system or 'Body-on-a-Chip' would be of tremendous benefit to the drug discovery and toxicology industries, as well as providing a more biologically accurate model for the study of disease as well as applied and basic biological research. Here, we describe the advances our team has made towards this goal, as well as the most pertinent issues facing further development of these systems. Description is given of individual organ models with appropriate cellular functionality, and our efforts to produce human iterations of each using primary and stem cell sources for eventual incorporation into this system. Advancement of the 'Body-on-a-Chip' field is predicated on the availability of abundant sources of human cells, capable of full differentiation and maturation to adult phenotypes, for which researchers are largely dependent on stem cells. Although this level of maturation is not yet achievable in all cell types, the work of our group highlights the high level of functionality that can be achieved using current technology, for a wide variety of cell types. As availability of functional human cell types for in vitro culture increases, the potential to produce a multiorgan in vitro system capable of accurately reproducing acute and chronic human responses to chemical and pathological challenge in real time will also increase.

Morphological and functional characterization of human induced pluripotent stem cell‐derived neurons (iCell Neurons) in defined culture systems

“…This stability is important for body-on-a-chip devices where stable populations are necessary to facilitate long-term assessment of drug effects. [1][2][3][4] Typical neuronal morphology was observed across all biological and chemically modified surfaces and media types examined. However, differences in neurite outgrowth were observed across examined culture surface and medium combinations.…”

“…Between 7 and 28 DIV, the number of neurons, as a percentage of the cultured cell population remained constant, suggesting the absence of proliferative neuronal precursor cell types. This stability is important for body‐on‐a‐chip devices where stable populations are necessary to facilitate long‐term assessment of drug effects …”

Personalized radiotherapy: concepts, biomarkers and trial design

“…A technological approach that has been increasingly commented on recently is human microphysiological systems, which are microscale "on-chip" models of human multiorgan systems; 104 however, the potential of such three dimensional organ platforms in prediction of tissue perturbations to external stimuli needs extensive developmental experimentation. 105,106 It is also argued that the zebrafish embryo system may be a tool for pre-clinical toxicity assessment. 107 Relevant acute and late normal tissue effects of combined-modality therapy have been demonstrated in mice as a model organism.…”

Biomimetic Tissue–Engineered Systems for Advancing Cancer Research: NCI Strategic Workshop Report

“…Shuler (Cornell University, Ithaca, NY, USA) reviewed the concept of “body-on-a-chip” and discussed the importance of utilizing “physiologically based pharmacokinetic models” to integrate multiple organ representations into a system with common, defined cell culture media. This is important for accurately mimicking organ metabolism and function when assessing a tissue construct’s response to genetic manipulation or exposure to cancer therapeutics (18). …”