Self-contained, low-cost Body-on-a-Chip systems for drug development

Abstract

Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs. The ability to operate a system for significant periods of time (up to 28 d) will provide potential to estimate chronic as well as acute responses of the human body. Here we review progress towards a self-contained low-cost microphysiological system with functional measurements of physiological responses. Impact statement Multi-organ microphysiological systems are promising devices to improve the drug development process. The development of a pumpless system represents the ability to build multi-organ systems that are of low cost, high reliability, and self-contained. These features, coupled with the ability to measure electrical and mechanical response in addition to chemical or metabolic changes, provides an attractive system for incorporation into the drug development process. This will be the most complete review of the pumpless platform with recirculation yet written.

Multiorgan microfluidic platform with breathable lung chamber for inhalation or intravenous drug screening and development

“…Microfluidic organ‐on‐a‐chip systems have been introduced to replicate some of the cellular and organ to organ interactions that can occur when a body is exposed to pharmaceuticals (Esch, King, & Shuler, ; Wang, Carmona, Hickman, & Shuler, ; Wang et al, ). These devices can be modified to contain a breathable lung device to study lung physiology, disease, drug therapy and potentially inhalation drug therapy.…”

“…Microfluidic organ-on-a-chip systems have been introduced to replicate some of the cellular and organ to organ interactions that can occur when a body is exposed to pharmaceuticals (Esch, King, & Shuler, 2011;Wang, Carmona, Hickman, & Shuler, 2018;Wang et al, 2017).…”

A robotic platform for fluidically-linked human body-on-chips experimentation

“…multi-organ, HuBoC systems that recapitulate organ-level functions to facilitate studies of drug pharmacokinetics and pharmacodynamics (PK/PD) in vitro [6][7][8][9][10][11] . An automated experimental system that can meet these goals needs to be highly multifunctional and must ideally enable fluid handling and sample collection, perfusion of fluid through multiple linked microfluidic Organ Chip devices, and tissue imaging, all within a controlled temperature, humidity, and CO2 environment.…”

“…An automated experimental system that can meet these goals needs to be highly multifunctional and must ideally enable fluid handling and sample collection, perfusion of fluid through multiple linked microfluidic Organ Chip devices, and tissue imaging, all within a controlled temperature, humidity, and CO2 environment. Custom assemblies using syringe pumps 12 , peristaltic pumps 13 , micropumps 11,14,15 , and gravity feed 10,16,17 , including several commercial platforms 18,19 , can be used to perfuse and link microfluidic tissue and organ culture inside incubators; however, these systems do not facilitate the features necessary for complex HuBoC experimentation. In particular, these systems offer limited ability to sample the different biological compartments or the capacity to reconfigure the system so that the same platform can be used for multiple experimental designs.…”

“…In particular, these systems offer limited ability to sample the different biological compartments or the capacity to reconfigure the system so that the same platform can be used for multiple experimental designs. Other HuBoC systems have used manual or automated transfer of fluid flow between multiple microfluidic culture systems using gravity feed 10,16 or they relied on perfusion through integrated microfluidic networks controlled by microvalve pumps 14,19,20 . But in these systems the shared medium containing drugs was transferred directly from one parenchymal tissue type to another without passing across a vascular endothelium as normally occurs in vivo.…”