Fluid dynamic design for mitigating undesired cell effects and its application to testis cell response testing to endocrine disruptors.

Microfluidic devices have emerged as powerful tools for cell-based experiments, offering a controlled microenvironment that mimic the conditions within the body. Numerous cell experiment studies have successfully utilized microfluidic channels to achieve various new scientific discoveries. However, it has been often overlooked that undesired and unnoticed propagation of cellular molecules in such bio-microfluidic channel systems can have a negative impact on the experimental results. Thus, more careful designing is required to minimize such unwanted issues through deeper understanding and careful control of chemically and physically predominant factors at the microscopic scale. In this paper, we introduce a new approach to improve microfluidic channel design, specifically targeting the mitigation of the aforementioned challenges. To minimize the occurrence of undesired cell positioning upstream from the main test section where a concentration gradient field locates, an additional narrow port structure was devised between the microfluidic upstream channel and each inlet reservoir. This port also functioned as a passive lock that hold the flow at rest via fluid-air surface tension, which facilitated manual movement of the device even when cell attachment was not achieved completely. To demonstrate the practicability of the system, we conducted experiments and diffusion simulations on the effect of endocrine disruptors on germ cells. To this end, a bisphenol-A (BPA) concentration gradient was generated in the main channel of the system at BPA concentrations ranging from 120.8 µM to 79.3 µM, and the proliferation of GC-1 cells in the BPA gradient environment was quantitatively evaluated. The features and concepts of the introduced design is to minimize unexpected and ignored error sources, which will be one of the issues to be considered in the development of microfluidic systems to explore extremely delicate cellular phenomena.

Fluid dynamic simulation for cellular damage due to lymphatic flow within the anatomical arrangement of the outer hair cells in the cochlea.

Damage to the sensory hair cells in the cochlea is a major cause of hearing loss since human sensory hair cells do not regenerate naturally after damage. As these sensory hair cells are exposed to a vibrating lymphatic environment, they may be affected by physical flow. It is known that the outer hair cells (OHCs) are physically more damaged by sound than the inner hair cells (IHCs). In this study, the lymphatic flow is compared using computational fluid dynamics (CFD) based on the arrangement of the OHCs, and the effects of such flow on the OHCs is analyzed. In addition, flow visualization is used to validate the Stokes flow. The Stokes flow behavior is attributed to the low Reynolds number, and the same behavior is observed even when the flow direction is reversed. When the distance between the rows of the OHCs is large, each row is independent, but when this distance is short, the flow change in each row influences the other rows. The stimulation caused by flow changes on the OHCs is confirmed through surface pressure and shear stress. The OHCs located at the base with a short distance between the rows receive excess hydrodynamic stimulation, and the tip of the V-shaped pattern receives an excess mechanical force. This study attempts to understand the contributions of lymphatic flow to OHC damage by quantitatively suggesting stimulation of the OHCs and is expected to contribute to the development of OHC regeneration technologies in the future.