Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy. Indeed, several microdevices are being developed specifically for clinical use to test novel cancer therapeutics. To be effective, these platforms need to replicate the continuous interactions that exist between tumor cells and non-tumor cell elements of the tumor microenvironment through direct cell–cell or cell–matrix contact or by the secretion of signaling factors such as cytokines, chemokines and growth factors. Given the challenges of personalized or precision cancer therapy, especially with the advent of novel immunotherapies, a critical need exists for more sophisticated ex vivo diagnostic systems that recapitulate patient-specific tumor biology with the potential to predict response to immune-based therapies in real-time. Here, we present details of a method to screen for the response of patient tumors to immune checkpoint blockade therapy, first reported in Jenkins et al. Cancer Discovery, 2018, 8, 196–215, with updated evaluation of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and expanded evaluation of tumor–immune interactions using RNA-sequencing to infer changes in the tumor–immune microenvironment. We also examine some potential improvements to current systems and discuss the challenges in translating such diagnostic assays to the clinic.

3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade

United States Defense Advanced Research Projects Agency Microphysiological Systems Program (W911NF-12-2-0039)

Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS)

The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

The unmet demand for the development of advanced in vitro models that emulate key features of human (patho‐)physiology and organ or tissue functionality led to the emergence of organ‐on‐a‐chip screening platforms. This biomimetic microtechnology enables accurate prediction of human responses, even at the multitissue or organ interaction level. With these advances, the necessity of incorporating biosensing within these platform becomes increasingly evident, to ultimately allow in situ, noninvasive, monitoring of cells, tissues and organs’ behavior. Seamlessly integrated biosensors on‐chip also offer the prospect of uninterrupted and fully automated analysis. The continuous search for biosensors that not only avoid disruptive analyses, but are also highly sensitive and permit instant in situ evaluation, steered further developments of optical biosensors including bioluminescence (BL). BL is particularly suitable to interrogate biological systems at the multiparameter level and it is well matched to address the intrinsic biological systems’ heterogeneity due to its inherent high signal to background ratio, to which the demand of simple measurement equipment can be added. Moreover, BL can be effortlessly integrated into any available organ‐on‐a‐chip platform and provides unique groundbreaking means for online monitoring, at the cellular level, and/or detection of cell secreted/excreted compounds. This review depicts recent advances in biosensors, with particular focus on BL. We highlight current challenges and future directions, aimed at stimulating the application of BL to interface organ‐on‐a‐chip systems, leading to the exponential advancement of both fields.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/VIW.20200177

New bioimaging avenues for organs-on-chips by integration of bioluminescence

The emerging technique of microfluidics offers new approaches for precisely controlling fluidic conditions on a small scale, while simultaneously facilitating data collection in both high-throughput and quantitative manners. As such, the so-called lab-on-a-chip (LOC) systems have the potential to revolutionize the field of biotechnology. But what needs to happen in order to truly integrate them into routine biotechnological applications? In this chapter, some of the most promising applications of microfluidic technology within the field of biotechnology are surveyed, and a few strategies for overcoming current challenges posed by microfluidic LOC systems are examined. In addition, we also discuss the intensifying trend (across all biotechnology fields) of using point-of-use applications which is being facilitated by new technological achievements.

Microfluidics in Biotechnology: Quo Vadis.

Limitations of the current tools used in the drug development process, cell cultures, and animal models have highlighted the need for a new powerful tool that can emulate the human physiology in vitro. Advances in the field of microfluidics have made the realization of this tool closer than ever. Organ-on-a-chip platforms have been the first step forward, leading to the combination and integration of multiple organ models in the same platform with human-on-a-chip being the ultimate goal. Despite the current progress and technological developments, there are still several unmet engineering and biological challenges curtailing their development and widespread application in the biomedical field. The potentials, challenges, and current work on this unprecedented tool are being discussed in this chapter.

Organ-on-a-Chip.

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