The goal of organ on a chip devices
The goal of organ-on-a-chip devices is to recapitulate tissue- and organ-level functions in a simple, yet easily manipulated apparatus. The simplest systems involve the growth of one or more cell types in a single, perfused microfluidic chamber to exhibit the functions of one tissue type. More complex devices can involve multiple cell types that are separated by porous layers that mimic basal membranes of barrier rock pathway (Bhatia and Ingber, 2014). These multi-channel chip devices allow for models of tissue–tissue or tissue–blood interactions and barrier functions and will be the main focus of this review. Additionally, through the connection of these individual organ-on-a-chip devices, recent studies are showing the possibility to observe organ–organ crosstalk. Barrier tissues are of great interest to researchers because they are essential in understanding transport between tissues or tissue and blood, ADMET (absorption, distribution, metabolism, elimination and toxicology), and barrier integrity and function. Here, we will investigate the role of microfluidic technologies and other in vitro methods in the modeling of fluid-to-tissue interfaces from the last few years, specifically with examples in the modeling of skin, lung, gastrointestinal, kidney, endothelium and blood/brain interfaces. We will highlight some of the recent developments in the field, as well as the barriers and challenges faced with the adoption of these relatively new technologies. Additionally, we will discuss positive trends as well as lessons for future microfluidic and in vitro technologies in the modeling of barrier tissues.
Applications The applications and need for microphysiological devices are potentially far-reaching. These devices may offer improved predictive power for responses of human tissues compared to currently used test methods (both cell-based assays and animal testing). Tests with improved predictive power are desired because current attrition rates in late-stage pharmaceutical testing are high. Based on the results of pharmaceutical studies from 1960 to 2000, it was determined that 25% of drugs entering clinical development fail due to lack of efficacy, 20% from toxicology, and 12% due to clinical safety issues (Kola and Landis, 2004), and testing methods have not changed significantly since then. This year, it was reported by CMR International that even after the ‘First human dose’ (toxicity testing, phase I), there is only a 7% chance for a drug to make it to market, and this only slightly increases to 17% after the ‘First patient dose’ (efficacy testing, phase II) (Fig. 1) (CMR International, 2015). By this time, a large amount of time and money has been invested in the product. The cost to take a compound from concept to market is on average $2.5 billion as reported in the Tufts CSDD 2014 cost study, dwarfing the $802 million estimate in its last major study in 2003, even after being adjusted for post-approval expenses and other costs linked to approval outside of the US market (DiMasi et al., 2014). Additionally, the time required to bring a drug to market is substantial; 10–15years on average. To reach phase I of clinical testing, it takes an average of 4–6years (PhRMA, 2015) which goes against the ‘fail fast, fail cheaply’ goal of pharmaceutical companies in weeding out flawed products. No company wants to invest millions of dollars only to find that a drug falls flat in clinical trials, or worse yet, after the drug hits the market. When comparing financial investments to current attrition rates, it becomes clear that more predictive tests need to be implemented. To help direct these studies and possibly eliminate drugs showing toxicity and/or lack of efficacy early, organ-on-a-chip devices with human cells could be used in the evaluation of new drug therapies, vaccines and other biologic agents in a more cost effective, and time efficient manner during pre-clinical testing.