Research On Modular Organ-on-a-chip Based On Universal Standardized Interface And Novel Bioreactors

Due to the ability to simulate human organs / tissues with microphysiological functions and 3D microstructures in vitro,organ-on-a-chip based on microfluidics and tissue engineering technology have been widely used in the biomedicine field.At present,many human organs can be reconstructed in vitro and related researches are conducted,however,since the field of organ-on-a-chip is still in a rapid development stage,especially in terms of commercial applications,the assembly and construction of the organ-on-a-chip and the optimization design of the structure is valuable in research and application.Therefore,this paper has carried out related research on the modular design of multi-organ chips and the novel microfluidic bioreactor for organ-on-a-chip applications:The modular-based multi-organ-on-chips enables more stable and flexible configuration to better mimic the complex biological phenomena.However,the existing magnetic-based interconnection mode is mainly realized by embedding the magnet directly into the microfluidic chip,which will inevitably increase the complexity and cost during the manufacturing process.In this paper,we design a reusable standardized universal interface module(RSUIM),which integrates the magnetic interconnection interface into a reusable PMMA module,combines it with a universal organ-on-a-chip in two ways,pasting or clamping,and further connect it with other general function modules.The interface module,as a standardized universal interface,has great expansibility: it can not only be assembled with a universal single organ chip,but also realize flexible plug-and-play configuration in a multi-organ system.In order to verify the effectiveness of the RSUIM,characterization of mechanical properties and vascularization model are first constructed in a universal vascularized organ-on-a-chip device,and a drug screening application is further performed in the microvascular tumor model cocultured with tumor cells,demonstrating its potential role in drug development.Microfluidic channels and tissue chambers in traditional bioreactors are often interconnected in a single layer,which will greatly reduce the flexibility of organ chip design.In this paper,two novel types of microfluidic bioreactors are presented,different from the conventional single-layer bioreactors,which separate the microfluidic channels and tissue chambers up and down,and respectively construct the microfluidic channel-tissue chamber structure and the microfluidic channel-porous membrane-tissue chamber structure,which will realize more flexible connection and location relationship.Compared with the traditional single-layer design with point-to-point mode,the line-to-line contact characteristics in the two-layer microfluidic bioreactor will result in more uniform line-to-line flow profiles and higher interstitial flow velocity,which is closer to the human internal environment ideal condition.In the multilayer bioreactor,a porous membrane is utilized as a connection channel between the microfluidic channel layer and the tissue chamber layer,which can realize large-area medium perfusion and flexible coculture interface.In addition,the design verified the feasibility of the novel bioreactor via a simple hydrogel perfusion experiment.