• We have developed original manufacturing techniques for bio-hybrid MEMSs that utilize special functions of bio-elements, proteins and living cells, for molecular selective sensing and power generation from natural fuels.
• (1) Conducting polymer electrodes printed on hydrogels (image 1)
• (2) Dynamic control of bio-adhesion by electrochemical means (image 2)
• (3) Micro Biofuel Cells with flexible enzyme electrode patches (image 3)

We hope to conduct collaborative research with a willing company for a practical application of these technologies in industry.

By applying nanoscale surface modification to individually designed 3D-printed titanium implants based on CT data, a biomimetic microenvironment is recreated, enabling regeneration of periodontal ligament-like tissue through host stem cell induction. This provides a novel treatment approach without cell transplantation for cases where existing implants are difficult to adapt.

Conventional implant treatment assumes direct bonding with bone, thus disregarding the regeneration of periodontal tissues such as the periodontal ligament. Furthermore, some patients avoid treatment due to concerns about bone-cutting surgery and multiple invasive procedures. This technology utilizes a nano-surface to induce stem cells, forming periodontal tissues similar to natural teeth. This enables the restoration of natural occlusal sensation through a single minimally invasive procedure.

• Custom-designed for each patient's root morphology, it reproduces natural force transmission and chewing sensation. Furthermore, by utilizing nanostructures to control cell adhesion and differentiation, it enables periodontal tissue reconstruction without the need for cell transplantation or regenerative factor administration.

In the future, we aim to collaborate with implant manufacturers to advance mass-production prototyping and quality evaluation, targeting practical application as a medical device. We also seek partnerships with companies and management talent who can jointly undertake strategic planning and clinical deployment for commercialization.

• Maintaining genetic diversity within a species is a major issue to conserve biodiversity and sustainable use. To monitor genetic diversity in natural and captive populations using adequate genetic markers is the most important step. We have focused aquatic organisms and studied the genetic diversity using an array of DNA analyses. Our research interest includes 1) genetic structure and phylogeography of natural populations in marine and freshwater organisms and 2) genetic management of commercially important species to contribute the stock enhancement programs.

Our skill can be applied to environmental assessment and fish resource management. We are collaborating with national institutes and giving advice to private environmental assessment companies.

• To generate a rice plant suitable for efficient biofuel production from its straw, we examined effects of overexpression of cellulase on saccharification of straw. The transgenic plant constitutively overexpressing cellulase showed enhanced saccharification, but various physiological and morphological abnormalities were also observed. To overcome this problem, a senescence-inducible promoter was used to express the cellulase. The plants successfully avoided the problem and showed enhanced saccharification after senescence.

Rice straw will be an efficient material for biofuel production. This method can be applied to other plants. In combination with highly engineered microorganisms for saccharification and fermentation, this method will contribute to efficient production of biofuels.

• A large number of microorganisms inhabit the oral cavity, such as the teeth, gingiva and tongue, in the form of oral biofilm. The oral cavity forms an ecosystem where the host (humans) and parasites (microorganisms) coexist. Disruption of the balance of this oral ecosystem leads to dental caries, periodontal diseases and oral malodor, and even deterioration of dental materials.
• Using leading-edge techniques of anaerobic experimental systems including original and unique devices, as well as the notion of "omics" such as metagenomics and metabolomics, we conduct research on oral biofilm functions. Knowledge of oral biofilms, from "what are they?" to "what are they doing?", enables us to address their control, that is, prevention of and therapy for oral biofilm-associated diseases.

Risk assessment of oral biofilm-associated diseases, such as dental caries, periodontal disease, oral malodor and aspiration pneumonia
Effects of medicine and food ingredients on oral biofilm function
Evaluation of biofilm-mediated material deterioration

• We have developed original manufacturing techniques for bio-hybrid MEMSs that utilize special functions of bio-elements, proteins and living cells, for molecular selective sensing and power generation from natural fuels.
• (1) Conducting polymer electrodes printed on hydrogels (image 1)
• (2) Dynamic control of bio-adhesion by electrochemical means (image 2)
• (3) Micro Biofuel Cells with flexible enzyme electrode patches (image 3)

We hope to conduct collaborative research with a willing company for a practical application of these technologies in industry.

Cells comprising biological tissues are surrounded by a structure known as the stroma, and their behavioradapts in response to stimuli generated by flow and transport phenomena. Despite its importance, ourunderstanding of how cells respond to their surrounding microenvironment remains limited, hindering thedevelopment of effective disease prevention and treatment strategies. A significant challenge has been thedifficulty in observing cellular behavior while simultaneously controlling the local culture environment.Although microfluidic devices have become increasingly prevalent in recent years, they have not fullyaddressed the need for comprehensive environmental control. To overcome this limitation, we developed the"stromal function chip," which focuses on three critical environmental factors within the stroma: oxygenconcentration, pH, and interstitial flow. This innovative platform enables precise and rapid manipulation ofthese parameters while facilitating real-time observation of both individual cellular responses and complexcell-cell interactions.

Traditionally, stage incubators mounted on microscopes have been employed to maintain culture conditionsduring time-lapse observations of cellular behavior. However, these conventional systems present significantlimitations in actively and rapidly controlling localized changes within the culture microenvironment. Whilerecent advances in microfluidic devices and organ-on-a-chip technologies have enhanced our ability toobserve cellular responses under controlled conditions, these approaches still exhibit considerable constraintsin achieving comprehensive environmental regulation. In contrast, our newly developed chip providesprecise, dynamic, and immediate control over the culture microenvironment during cellular experiments,enabling high-fidelity visualization and quantification of complex cellular dynamics in response to environmental stimuli.

• The stromal function chip features sophisticated architecture comprising cell culture channels with multiplegas channels strategically positioned in vertical alignment above them. Through the controlled delivery ofprecisely mixed gases containing specific oxygen and carbon dioxide concentrations to these gas channels,the chip facilitates gas exchange that enables exquisite regulation of both oxygen concentration and pHwithin the cell culture microenvironment. This approach represents a significant advancement overconventional chemical reaction-based methods, as it eliminates potential cellular toxicity while providinghighly flexible and dynamic control over oxygen concentration and pH. Furthermore, the chip's innovativedesign allows for the precise modulation of interstitial flow—achieved by embedding hydrogel within theculture channels and establishing controlled hydrostatic pressure gradients between inlet and outlet ports. Bysimultaneously manipulating these three critical environmental factors—oxygen concentration, pH, andinterstitial flow—researchers can systematically investigate cellular response mechanisms and characterizehow cells adapt to specific stromal microenvironmental conditions, thereby advancing our understanding oftissue physiology and pathophysiology.

By precisely recapitulating the hypoxic and acidic microenvironmental conditions that characterize tumorniches and inflammatory sites, this innovative chip serves as a powerful platform for pre-clinical evaluationof therapeutic efficacy, enabling researchers to determine optimal drug candidates and dosage regimens priorto in vivo studies. Moreover, the system serves as a platform/tool for fundamental medical and biologicalinvestigations, allowing for high-resolution cellular observation and analysis under rigorously controlled andphysiologically relevant culture conditions.

• "Features"
• High-resolution imaging of biological tissue is non-invasively obtained with high frequency ultrasound. We have developed some ultrasound microscope systems which realized the resolution of 15-micron with 100 MHz and resolution to visualize a single cell with GHz range ultrasound. Ultrasonic imaging provides not only tissue morphology but also information on tissue elasticity. Recently, we have developed a real-time three-dimensional photoacoustic imaging system for visualization of subcutaneous micro vasculature and oxygen saturation.
• "Targeted Application(s)/Industry"
• High frequency ultrasound and photoacoustic imaging is repeatedly and non-invasively applied for early diagnosis of atherosclerosis, skin aging and tissue metabolism. They are useful for efficacy assessment of cosmetics and pharmaceuticals. High frequency ultrasound is also applied in the industrial areas where thickness measurement of opaque film or bilayer thin coating with the precision of 0.1 micron is required.

• To generate a rice plant suitable for efficient biofuel production from its straw, we examined effects of overexpression of cellulase on saccharification of straw. The transgenic plant constitutively overexpressing cellulase showed enhanced saccharification, but various physiological and morphological abnormalities were also observed. To overcome this problem, a senescence-inducible promoter was used to express the cellulase. The plants successfully avoided the problem and showed enhanced saccharification after senescence.

Rice straw will be an efficient material for biofuel production. This method can be applied to other plants. In combination with highly engineered microorganisms for saccharification and fermentation, this method will contribute to efficient production of biofuels.