Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Abstract

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

Vascularisation of pluripotent stem cell–derived myocardium: biomechanical insights for physiological relevance in cardiac tissue engineering

“…Meanwhile, there is great potential for integration of optical measurements and biochemical sensors in microfluidic chips [38], allowing real-time evaluation of structure and function of both the CM and EC under hemodynamic forces. An example of this is simultaneous observation of EC barrier function (via trans-endothelial electrical resistance (TEER) measurement) and myocardial conduction velocity (via multi-electrode array (MEA)) [112].…”

“…Incorporation of physically relevant biomechanical conditions can be achieved through use of deformable 3D biomaterial substrates, and perfusable microfluidic and bioprinted cultures. The experimental versatility of microfluidic platforms and OOCs is particularly high, with models incorporating integrated and automated sensing systems to monitor metabolic activity, oxygen levels, electrophysiology, and mechanical activity [38]. The combination of integrated sensing and precisely controlled flow conditions will allow researchers to dissect the role of biomimetic haemodynamics in myocardial-microvascular interaction.…”

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“…The field of microphysiological systems (MPS) (also known as “organs-on-chip”) combined with advancements on bioprinting can be instrumental in the development of novel advanced models that more closely resemble human tumor–immune interactions, and that allow the modular integration of several immune “organs” or compartments [ 165 , 196 , 206 ]. At the moment, the main challenge of this technology is the implementation of sensors for live monitoring of cellular processes, which can be based on the miniaturization of existing analytical techniques or in the integration of novel biosensors [ 207 ]. By bringing together the potential for broad customization of culture conditions, the advantage of miniaturization and throughput (compared with traditional bioreactors or culture plates), and the possibility of replicating different biological compartments of the TME in the same system [ 208 , 209 ], MPS technology may be a starting platform to refocus on basic and applied human immunology research [ 165 , 196 ].…”

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“…105 Additionally, organon-chips device have also been well-established simply to impersonate the more complex organ systems, since the excellent capability of the biosensors and microuidic system. 106,107 These advances make the in vitro environment to be one of the plausible choices for biosensor development.…”