Research
Reproduction of in-vivo microenvironment using microfluidic devices
Cells in the body sense and respond to mechanical stimuli caused by movement and blood flow, and chemical stimuli caused by chemicals. Normal cell responses are essential for differentiation, morphogenesis, and maintenance of biological homeostasis, and if these functions are disrupted, it can cause the onset of diseases and various damages. In our laboratory, we are developing a microfluidic device "3-in-1 biological simulating chip" that reproduces both physiological and pathological environments by controlling three factors: oxygen partial pressure, mechanical stimulation, and chemical stimulation. This chip is expected to contribute to the elucidation of phenomena in the in vivo microenvironment and be applied as a basis for drug discovery such as drug screening.
Microscopic image of the 3-in-1 biological simulating chip (upper figure) and the microvascular network formed within the chip (lower left figure), time-lapse observation system for 3D dynamics of cell groups (right figure)
Elucidation and control of hypoxic response of cell groups
The oxygen concentration inside living tissues is lower than that in the atmosphere, changes both temporally and spatially, and affects cellular activity. For example, inside a cancer tissue (cancer microenvironment), excessive cell proliferation and the formation of an immature vascular network result in uneven distribution of oxygen concentration (spatial changes), acute hypoxic stress, and reoxygenation ( change over time) is occurring. Temporal and spatial changes in oxygen concentration activate cancer cell migration and angiogenesis, promoting cancer growth and metastasis. Therefore, in this research, we are working on clarifying changes in cell dynamics and properties depending on oxygen concentration, such as cancer cell migration and the substance permeability of vascular endothelial cell monolayers, and investigating ways to control these changes.
Growth of cancer cells in a hypoxic environment (upper left figure), measurement results of cancer cell migration under oxygen conditions (upper right figure) and vascular endothelial cell migration (lower left figure), and morphology of vascular endothelial cells depending on oxygen conditions Change (lower right diagram)
Hemodynamic analysis by combining medical measurement and numerical analysis
Overcoming circulatory system diseases, which are obstacles to blood flow essential to sustaining life, is an important issue that is essential for realizing a healthy society. Even with medical devices that have advanced dramatically in recent years, it is difficult to completely measure information about blood flow within a living body. Furthermore, even if ultra-high-speed calculations (real-time calculations) are made possible by high-performance supercomputers, since the exact calculation conditions are unknown in reality, it is difficult in principle to completely reproduce blood flow in a living body. In this research, we are conducting research to elucidate the complex blood flow in living bodies and realize advanced medical care through measurement-integrated simulations that integrate measurement and calculation.
Analysis flow of the 2D ultrasonic measurement integrated blood flow analysis system (upper figure), photo of the constructed system (lower left figure), and numerical experiment results for reproducing wall shear stress distribution by 3D ultrasonic measurement integrated blood flow analysis (right) (Figure below)