Aligned with the vision of Internet of Things, it is expected that the number of interconnected devices, equipped with sensing and actuation functionalities, will grow beyond trillions of units by 2025 representing about 1000 devices per person in the world. The need for personalization that inevitably ensues necessitates devising novel manufacturing processes that seamlessly integrate such functionalities into our surrounding objects. To this end, 3D printing is an excellent process, as it is capable of rapid and on-demand production of mechanically sophisticated and personalized objects with efficient use of materials. In this study, we propose fabrication method of smart devices based on a 3D printing and demonstrate an earable device for real-time monitoring of body temperature, and a wearable device for multi-vital monitoring of newborn baby.

The bonding ability of metallic biomaterials, which have excellent mechanical property and durability, onto hard tissues has been improved by surface treatments and the treatment methods have been applied onto the metallic implants for hard tissues. On the other hand, the adhesion ability of metallic biomaterials onto soft tissues has not been demonstrated so far. However, metallic implants are also frequently used in a state of being fixed to soft tissues such as subcutaneous and blood vessels. In this study, we report that soft tissue adhesion ability of titanium, which has excellent biocompatibility among metallic biomaterials, could be significantly improved by a chemically treatment.

Metronomic photodynamic therapy (PDT) that uses a photosensitizing agent and light requires local and long-term photoirradiation to the target tumor by stable fixation of optical devices in the body. In this study, we developed tissue-adhesive and wirelessly powered optical devices that can be fixed onto the biological tissue surfaces without suture in the animal body. Wirelessly powered LED chips were sealed with polydopamine-modified polydimethyl siloxane nanosheets (~600 nm thick). The devices were subcutaneously implanted in the intradermal tumor model mice, therefore the LEDs were placed just beneath the tumors. After administration of a photosensitizer (photofrin) into the mice, the implanted optical devices locally irradiated the target tumors for 10 days at approximately 1,000-fold lower intensity than conventional PDT, leading to remarkable tumor regression including complete disappearance. Such a fully-implantable metronomic PDT system is expected to be applied for deeply located tumors that conventional optical devices could not reach.

Several wireless systems like medical telemetry, PHS system, Wifi system are operated in medical field. These systems are effective to improve medical efficiency. Especially, UHF band passive RFID has high performance than usually HF band passive RFID. Tracking of human, small sized ME equipment and SPD can be realized using this new RFID system. Surgical equipment management can be also realized. These systems are effective for decline of human error in medical field. Stealth bar code is also effective for medical individual identification.

Purpose: RFID was evaluated for problems on clinical conditions, for usage RFID as patient name wristband in department of radiology.

Method: We had experiments for disability shadows of images, tag damages, exothermic reactions on clinical conditions as X-ray simple photograph(X-p), X-ray computedtomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography/computed tomography (PET/CT), scattered radiation of 10Mev X-ray Liniac for Radiation Therapy (Lniac).

Result: HF band tag was shown disability shadows of images in X-p, but UHF band tag wasn't. Disability shadows of images, RFID tag damages weren't confirmed inCT, MRI, PET/CT, Lniac. Exothermic reactions by radio frequency of MRI over 60 degree Centigrade were not identified.

Although the EMR is designed in terms of patient records, EMR access logs contains various valuable information in themselves. The time-series analysis is suitable for optimization not only of EMR terminal devices arrangement and allocation, but also of medical staff's work loads in hospitals. Clearly visualized much lower device occupancy rate than other units in the hospital might easier reallocation against non-evidence based objection. The analysis with a workers axis might reveal their overloads at the specific situation in everyday tasks series. The performance comparison among staffs is likely to be drawn hospital managers attention in terms of a personal evaluation. Because the workloads index from access logs is completely different from the individual performance ratio, the result of analysis has just to be restricted to reduce and to optimize the total workloads balance in the hospital.

In the era of Society 5.0, two study groups have been discussing the direction of business reform using inpatient devices in order to make nurses more capable. A questionnaire survey was conducted with nursing managers to understand their views on this issue. As a result, it was found that there was a certain level of understanding in implementing a motion detection system using RFID and an observation system using face recognition in hospital wards. On the other hand, there was a strong sense of resistance to leaving the nurses' own behavior log as compared to the patient's behavior, suggesting the need to strengthen privacy protection.

When we immobilize a broken bone in a cast or need to be on extended bed rest, we experience a rapid decrease in the mass and strength of skeletal muscle. This type of muscle wasting, called as disuse muscle atrophy, is suppressed by exercise, and its mechanisms have been studied well. In contrast, mechanisms of the muscle atrophy in space, which is likely caused by microgravity, remain to be solved.

In this meeting, we will introduce our project named "Zebrafish Muscle". Key questions of this project are whether skeletal muscle atrophy also occurs in zebrafish, tropical fresh water fish, under microgravity and how skeletal muscle response to gravity/microgravity. Comparison of transcriptome data during the space stay from its initial phase towards the recovery phase after return to the earth will illustrate fundamental features of skeletal muscle atrophy in space and roles of gravity in the maintenance/homeostasis of skeletal muscle on the earth.

In spaceflight and simulated microgravity experiments (3D clinostat), we found that the gene expression of dopamine metabolic enzyme decreases reproducibly compared to 1 G control in C. elegans. Exogenous dopamine application increases the gene expression strongly suggesting that it is negatively regulated in response to endogenous dopamine levels. Therefore, we think the working hypothesis that "dopamine is reduced in the microgravity environment", and in December 2018 we performed another C. elegans spaceflight experiment with collaboration of UK research team as Molecular Muscle Experiment. As a result, the spaceflown C. elegans showed a marked decrease in endogenous dopamine levels, similar to the case of ground 3D clinostat culture. Similarly, in Rossian biosatellite BION-M1 experiment, in addition to loss of bone and muscle mass, the rate-limiting enzyme of the dopamine synthesis and its degradation enzyme were also reduced in striatum of spaceflown mice. These results strongly suggest that the microgravity may affect metabolism of the neurotransmitter dopamine across species. In this presentation, we also mention the action mechanism of microgravity on dopamine reduction.

Although polysomnography (PSG) is the gold standard of sleep measurement for the diagnosis of sleep disorders, its application is limited due to several factors including i) disturbing sleep by loading many electrodes and sensors and by staying at a hospital room overnight, and ii) costing a lot and taking a long time to go through PSG in the hospital. We thus undertake development of a sleep measuring system that enables anyone to measure his/her natural sleep at home at a reasonable cost. To construct the sleep measuring system, we have developed following 2 core technologies; i.e., a) a wearable device for the EEG measurement at home, and b) an AI program to analyze EEG data for sleep staging. In the development of the wearable device, we made a trial product with built-in electrodes (Phase 1) to find problems of robustness of the measurement and comfort of use. We thus modified the prototype to a device with separate electrodes (Phase 1.5), which met our quality criteria. We studied sleep staging of PSG data by using the deep learning to develop a good analyzing model, which gave staging results with κ-index of 0.83 against staging results by skilled clinical laboratory technicians. We now develop a sleep staging model for the wearable device. We are also developing a system integrating the core technologies, the communication network, and interfaces for inputs/outputs of data and information.

Japan has introduced Clinical Trials Act in April 2018 with unique definition of "clinical trials". Once defined as a clinical trial, the research has to be conducted by ones with medical doctor license. As a result, the act discourages medical and biomedical engineering researchers, mostly engineering-origin researchers without medical doctor license, to engage in research activities. In order to promote medical and biomedical engineering researches, Japanese Society for Medical and Biomedical Engineering issued guideline for researchers to check whether a particular research is classified as clinical trial under the clinical trial act definition on October 2019. Although the guideline provides general classification criteria, contributions of members to develop detailed criteria should be given for each research approach, such as electric-stimuli, motor-assistance, etc. is expected. Keywords: The Clinical Trials Act of Japan, Guideline, Classification Criteria.

In order to consider the applicability of the medical practice in a study on a medical instrument, a supplementary table for evaluating its effect on the body structure and function has been developed. Specifically, a working group in safety investigation of electrical stimulus is developing the table about biomedical instrumentation and control using current flow in human body such as composition measurement by electrical impedance method, transcutaneous electrical stimulation, and functional electrical stimulation. The possible effects of excessive body conduction are skin injury, nerve injury, functional disturbance, pain, fibrillation, and so on. The working group has been widely investigated the range of safe body conduction based on the international and domestic standards and literatures. In this presentation, the author introduces a methodology for developing a supplementary table and its importance based on the investigated literatures about the safety and invasiveness of the electrical stimulus.

The law of the "Clinical Trials Act" in Japan was enforced from April 2018. The law has the penalty to the illegal acts in widespread fields associated with human studies. The range of its application covers not only medical care and diagnoses but also prevention. The judgment of whether our own studies should be applied or not will often annoy researchers in Japan. It will possibly daunt researches in these fields and then cause the quality of their studies to be degraded. The working group associated with the law to respond to the trouble in JSMBE has been started up. The members are trying to describe the guideline to assist the judgment for compliance. The authors are going to present the case studies on rehabilitation and care and welfare engineering and are strongly expecting to find efficient plans and policies to make the guideline supporting the participants.

Cells reside in a highly dynamic extracellular matrix microenvironment, where biochemical, physicochemical, mechano-structural cues are displayed in spatiotemporal fashion. To recapitulate this, dynamic culture platforms have emerged as powerful tool to probe and direct active changes in cell functions. Here, we briefly overview the cell manipulation technologies based on spatiotemporally tunable mechanobiomaterials with a focus on shape memory polymers.

Therapeutic properties of mesenchymal stem cells (MSCs) have close relations with the stemness, while which tend to deteriorate depending on the memory of mechanical dose from the culture matrix. To assure the maintenance of stemness of MSCs during usual expansion culture, it is essential to design the micromechanical environment to inhibit the lineage bias. For this issue, we have developed the microelastically-patterned hydrogels with triangular stiff domains on soft base, which drives both forward and reverse durotaxis of MSCs resulting in the nomadic migrations among different region of elasticity. This culture system was found to make MSCs more vigorous in terms of up-regulation in the genes relating to cell viability, prolifereation and motility including highest expression of core regulator of Wnt signaling, APC. In this talk, mechanisms of such exercising effects for MSCs and manner of the stemness maintenance during the nomadic culture on heterogeneous field of elasticity are discussed.

We elucidated the molecular mechanism of angiogenesis effects of non-contact compression force based on phased-array ultrasonic technologies. Endothelial cells cultured on type I-A collagen gel were induced to differentiate and form tube-like structures concomitant with the cyclic compression at apical cell-surface. Additionally, cyclic compression induced high-frequency Ca2+ oscillations which were reduced with the removal of compression. Cyclic compression by our device accelerated wound healing in an acute murine wound model. Compression-stimulated wounds demonstrated significantly accelerated wound healing: their mean area decreased significantly faster relative to control wounds. The histochemical staining indicated the facilitation of collagen proliferation and proangiogenesis in the treatment group. Gene expression profiling revealed similarities between the in vitro and in vivo. Notch ligand and Notch signaling that were involved in angiogenesis were sequentially and transiently upregulated in the early stage after starting treatment. Compression may stimulate to accelerate early angiogenesis mediated by Notch ligand upregulation.

Fully implantable MEMS devices of the artificial cochlear sensory epithelium have been developed in our research group both from the viewpoint of medicine and mechanical engineering. We successfully made the animal test and obtained the electrically evoked auditory brainstem response in the previous experiment. Further development is continued for the clinical applications. Investigation of characteristics of the resonance of the artificial bionic membrane, the ability of frequency selectivity and the electric output from the piezoelectric material is quite important, and their optimal design method should be developed for the prediction of the performance. As the technical barriers, the higher output electrical voltage for the stimulation of the auditory nerve, precise feedback mechanism mimicking the outer hair cells and the efficient electrodes for the nerve stimulation should be focused. In the present study, the remained problem to be solved in these barriers and the future perspective are discussed in detail.

A cell obtains chemical energy from outside, converts into ATP, and consumes for biological works. On the other hand, the rest of the energy is dissipated as heat, contributing to the rise in temperature inside a cell. From viewpoint of traditional thermodynamic law, the energy flow in which ATP and heat play an important role is underlying in cellular system. Recent years, we generated various fluorescent sensors that enable to detect the change of intracellular ATP dynamics and temperature inside cells as fluorescent detectable signals such as fluorescence intensity and lifetime. More specifically, our molecular-sized fluorescent temperature sensors allow the temperature mapping of thermo-generating cells like brown adipocytes and skeletal muscles. As for the other element, we engineered the red, green, and blue colorful genetically encoded ATP sensors and further demonstrated in the visualization of ATP dynamics of different organelles at the same cell.

Vascular endothelial cells (ECs) play critical roles in regulating a variety of vascular functions in response to hemodynamic forces, namely, shear stress and stretch. Endothelial plasma membranes have recently been shown to respond differently to shear stress and stretch, by changing their lipid order, membrane fluidity, and cholesterol content. Such changes in the membranes' physical properties trigger the activation of membrane receptors and cell responses specific to each type of force. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca²⁺ signaling within the cells. These results suggest the novel role of the mitochondria in transducing the shear stress into ATP generation.

We have established a hybrid live-cell imaging system by combining high-speed atomic force microscopy and confocal laser scanning microscopy. We have demonstrated that morphological changes of the plasma membrane during clathrin-mediated endocytosis and dynamics of cortical actin network could be visualized and analyzed with this system in a living cell. By utilizing this technique, together with a stretchable cell-culture chamber made of PDMS, we tried to elucidate how these dynamics and processes are sensing and responding to external mechanical stimulation.

Wall thickening of the artery walls in response to hypertension is thought to be driven by the medial smooth muscle cells (SMCs) sensing stress applied to themselves. It is thus necessary to know the stress applied to the individual cells in the wall. The artery wall mainly composed of SMCs, elastin, and collagen, whose Young's moduli are 10-100 kPa, 600 kPa, and 1 GPa, respectively. These components are intertwined with each other in a dimension of ~10 um. Thus, stress distribution in the wall should be very much complicated at a microscopic level. To know the stress applied to each SMC, we need to know 3D microscopic structure in the wall. We have been studying the microscopic structure by combining a 3D internal structure microscope, a multi-photon microscope, and a tissue clearing technique. In this talk, we will introduce these techniques and discuss their advantages and disadvantages.

Acoustic stimuli evoke nanoscale sinusoidal vibrations on cochlear sensory epithelium, which contains contractile outer hair cells (OHCs). The sensitivity of the vibration amplitude is amplified as the stimuli become weaker. Although this nonlinear property depends on the OHCs' motion, the mechanisms have not been fully elucidated. Using multiple vibrometers, we analyzed guinea-pig epithelium at the portion responsive to high-pitch sounds. Firstly, a laser interferometer we modified detected a static offset together with vibrations when loud sounds were applied. The offset was likely induced by a steady contraction of OHCs. This motion would suppress excess vibrations and protect the epithelium from damage. Secondary, with an improved commercial optical coherence tomography vibrometry, we visualized OHCs in the epithelium and detected that the vibration amplitude at the apical region of OHCs exceeded that at the basal region, when sound pressure was moderate. This profile may contribute to the amplification of the epithelial vibrations.

We examine the effectiveness of the application "MIMOSYS"(Mind Monitoring System), which monitors mental health status using voice, developed in our previous research. In order to verify the medical validity of MIMOSYS, the University of Tokyo has been conducting social implementation research from July 2015. In the beginning, MIMOSYS analyzed call voices on Android, and after updated to MIMOSYS ver.2, to support recording analysis in seven languages and iOS. By analyzing MIMOSYS ver.2 data, distribution in Japanese is not different from other languages, and weak correlation was observed between MIMOSYS results and self-administered test results; it suggested MIMOSYS ver.2 for iOS is also useful. Further, from the analysis of the effect on the results due to the difference in the recording analysis method, analyze from fixed phrases was slightly lower than free speech. Therefore, the effectiveness of using MIMOSYS in consideration of the difference in the recording analysis method was suggested.

In today's stressful age, early detection of mental health problems is an issue. We have developed MIMOSYS (Mind Monitoring System), which estimates a human's mental health condition by voice. This technology has the advantage of being noninvasive and easy to measure. On the other hand, MIMOSYS has a property that specificity of mental health index is low with short term speech data. In this study, we collected speech data of patients with major depressive disorder, found the likelihood distribution of Vitality of mild and severe individuals, calculated the posterior probability using Bayes' theorem from Vitality which obtained from the subject's utterance and estimated patients' severity. As a result, we confirmed that the separation performance improves more than Vitality itself. This result shows that it is possible to estimate mental health conditions with high precision from short term MIMOSYS data.

Saturated diving is a process in which a high-pressure living room with a pressure almost equal to the target depth is prepared to improve diving efficiency in great depths. Helium gas saturates in the diver's body under high pressure.

With the assistance of Japan Maritime Self-Defense Force, voice recordings of saturation divers during training were acquired and examined to study the impact of high pressure and helium absorption on our stress-evaluation method using voice.

This was analyzed after eliminating the numerous, extraneous training environment noises.

The results demonstrate that the voice evaluation value during training was generally lower compared to normal conditions. A slight value change due to the depth difference during training was also observed, but it was not possible to determine whether the change was due to a pressure difference or a change in mental state.

We analyze the crying voice of ADEL children before and after the Correction of the glosso-larynx (CGL) and clarify the difference to detect severe ADEL infants who have difficulty raising children. We recorded crying voices before and after CGL for infants who came to Mukai Clinic in hope of CGL, and cut out crying voices with less noise from the voice file.

In the analysis, we calculated five emotional features by Sensibility Technology (ST) software and four features related to sound quality by Praat software from voices. The mean value of each feature value before and after surgery was compared and examined by t-test for each of the 69 participants whose effective crying voice was confirmed before and after CGL treatment. As a result, significant differences were observed in some feature values. This result indicates that the crying voice changes depending on the displacement of the tongue and larynx.

1.PurposeIn recent years, the traffic accidents by the advanced age driver suspected to have cognitive impairment becomes a social problem. We developed a new method that predicts ability for driving from the voice that the person uttered. This method using the voice does not need specialized equipment, and there is the advantage that we can perform routinely, remotely and easily. 2.MethodAbility for driving by the driving simulator inspected 45 elderly people as a subject. In addition, we recorded their voice by the fixed form sentence reading aloud. We carried out machine learning as learning data with large number of voice features and driving test values and derived a classification model and a regression model.3.ResultsThe classification of the two level and the prediction by the regression model showed good results together.

Paper-based analytical devices (PADs), consisting of flow channels surrounded by hydrophobic barriers, are promising in the realization of point-of-care testing outside equipped laboratories because of their portability, easy disposal, and simplicity in fabrication and operation. The conventional detection scheme is colorimetry where color intensity depending on the analyte concentration represents quantitative information. However, colorimetry needs a scanner or a controlled light source for the reproducible image capture, and a personal computer for image processing. Therefore, in addition to colorimetric detection, we have developed several types of PADs using the detection schemes without instrument which are based on zone-counting readout and distance-based readout. We have also explored ways to enhance the sensitivity and to stabilize the reagents deposited on a paper substrate. Here, we overview our achievements in the study of PADs [1].

[1] T. Kaneta, W. Alhamad, P. Varanusupakul, Appl. Spectrosc. Rev., 54, 117-141 (2019). (DOI: 10.1080/05704928.2018.1457045)

Point of care testing, a rapid and easily accessible exam that provides a quick result to the patients, is an emerging technique in the medicare system. This technique facilitates better disease diagnosis, monitoring, and management. It enables more precise medical decisions, as the diseases can be diagnosed at a very early stage, leading to improved health outcomes for patients by allowing the immediate start of treatment. It also provides patients to monitor their disease control more efficiently. The finger sugar testing is an excellent example of these techniques. Diabetic patients can check their blood sugar at any time and anywhere and modify their anti-diabetic medication or insulin injection to avoid blood sugar over or under control. For the non-diabetic ones, or who are unaware of getting diabetes, they can check their fasting sugar at home and seek the doctor earlier if the rapid testing reported abnormal fasting sugar.

Urinary tract infection (UTI) is a common disease. The prevalence in women over 65years of age is approximately 20% and nearly 11% in the overall population. Meanwhile, UTI accounted for the second most of the cause of sepsis during hospitalization. The gold-standard diagnosis of urinary tract infection is made by clinical symptoms and positive results of urine culture. Because of the variety of clinical manifestations of urinary tract infection and the time-consuming urinary culture, the diagnosis of urinary tract infection is rather difficult. The current urinary dipstick was not reliable with low sensitivity in the diagnosis of UTI. Although empirical broad-spectrum antibiotics are effective in treating UTI, these uncertainties in determination lead to the overuse of antibiotics in clinical practice. Drug resistance pathogens are result from the overuse of antibiotics. Therefore, the more accurate and rapid test for UTI is urgent.

MTT+ Assay (3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromid) is a colorimetric assay for assessing cell metabolic activity. In other words, the method could quantify the living cell of the sample. Our Lab had applied this exam on the sperm mobility examination previously. In previous bacterial in vitro experiments, we had found the colorimetric result might be correlated to the concentration of bacteria. As a result, we plan to conduct an MTT assay for the urinary bacteria examination in vivo. With the rapid result of MTT assay, it could improve our current bacteriuria screen. We also plan to develop a Point-of- Care Testing device with MTT assay to exam the bacteriuria more efficiently.

Purpose

Endometriosis is one of most common gynecologic disease, and it can cause dysmenorrhea, infertility, and even malignant transformation that affect patient's life quality. The most common biomarker of endometriosis is serum CA-125 level. There were much increasing articles already presented that inflammatory factors including IL-1, IL-6, IL-8, and TNF-alpha as well as adhesion or angiogenesis factors involving ICAM-1, MMPs, TIMPs, and VEGF can be utilized. However, those studies usually spend much times with intervention approaches. Urine is the easiest collected specimen without invasion. Therefore, we want to developed quick test of endometriosis based on urine specimens.

Methods

In our present study, we also collected urine from patients of endometriosis to performed associate proteomics study to search a representative urinary biomarker as a non-invasive detection of endometriosis in our first step study. Then based on above results and our lab's previous experience, a paper-based quick examination test will be developed in our second step study. Besides, a further clinical trial to apply the paper-based test into patients with endometriosis will also be started in our third step study.

Results

In our first step of project, urine analysis started after collection of total 40 patients with clinical endometriosis including endometrioma or adenomyosis, and another 40 persons without endometriosis as controlled group. ELISA test with kit of CA-125, alpha1-antitrypsin (A1AT), Enolase-1, and vitamin D binding protein (VDBP) were used for collected urine specimen. Then much greater amount of alpha1- antitrypsin (A1AT), Enolase-1, and vitamin D binding protein (VDBP) can be detected in endometriosis group than controlled groups. The area under the curve was 0.815 (95% confidence interval 0.707 to 0.933) when evaluated with serum CA-125 combination.

Conclusion

Based on above results, further paper-based microfluidic quick test will be developed in our next step of project. Then further clinical trial will be started with this quick test in patients with endometriosis under different treatment status to validation of the clinical applications in the future.

Wound healing is a complicated process that involves various factors. Depending on the recovery time, the wound can be divided into acute wounds and chronic wounds. Unlike the conventional wound morphology assessment, we tried to assess the wound in a molecular aspect. Recent researches have indicated that growth factors play an important role in the wound healing process. Many cytokines like vascular epithelial growth factor (VEGF) and epidermal growth factor (EGF) have been reported to take part in angiogenesis or endothelial proliferation during the process of wound healing. Recent wound dressings development often combines growth factors, like platelet-derived growth factor (PDGF), to enhance the healing process. Therefore, we tried to detect the amount of specific cytokines like VEGF or EGF at the wound sites in order to provide a clinical reference for further therapeutic strategies. For example, the amount of EGF in chronic wounds is expected to be relatively low, by sensing the increasing of EGF, doctors could decide to conduct surgical debridement or EGF treatment. In terms of the importance of growth factors in wound healing, we tried to develop a point-of-care method that can be applied in wound healing diagnostic. The method was based on paper material because it is rather cheap and easy to manufacture.

The acute wound usually heals as it proceeds the normal process of wound healing. We targeted the biomarkers of angiogenin and VEGF, which have been reported to participate in the angiogenesis process of acute wounds. These protein biomarkers can be detected through immunoassay, and we transferred the assay into paper-based assay like paper-based ELISA or lateral flow immunoassay test strip. We had tried to use these methods to assess the burn depth of secondary burn wound through the detection of angiogenin. On the other hand, chronic wounds like diabetes ulcer foot are also big issues throughout the world. However, the recent diagnostic method is hard for point-of-care applications. In our study, we tried to define the amount of EGF in chronic wounds, and moreover, to develop a point-of-care diagnostic method for chronic wound care. EGF contributes to the proliferation of keratinocytes and plays a significant role in cell migration and differentiation. Therefore, EGF biomarker is an important factor that can even be used as treatments for chronic wounds. We tested the EGF concentration in chronic wounds with ELISA in microplates and developed a paper-based ELISA detection method of EGF for point-of-care application. We wish that our paper-based diagnostic method could offer a convenient way for wound care management and to improve wound healing

Malaria is a mosquito-borne infectious disease caused by parasitic protozoans of the genus Plasmodium, and parasitizes on red blood cells (RBCs). It is one of the major infectious diseases, with an estimated 216 million clinical cases and 445, 000 deaths. The African Region continues to bear an estimated 90% of all malaria cases and deaths worldwide, and the infrastructure to address the disease is weak in endemic area. A highly sensitive and accurate malaria diagnostic system which can be used in the endemic area is necessary. A fluorescent blue-ray optical system with scan disc including a push column for the recovery of RBCs from whole blood was developed. A portable, battery-driven fluorescence image reader was employed to detect Plasmodium falciparum-infected RBCs (Pf-iRBCs) for 40 min. The ability of the developed system to detect low-density Pf-iRBCs and provide accurate quantitative evaluation with easy operation was demonstrated.

Pathogens, chemicals and autoimmunity trigger T cell-driven inflammation in the skin under control of Dendritic Cells (DCs). No in vitro human model recapitulates cutaneous immune responses, as they lack an epidermal barrier, necessary to investigate topically applied compounds, and fail to acknowledge the influence of non-immune cells on DCs and T cells. This prevents accurate pre-clinical evaluation of drugs, adjuvants or chemicals. Therefore, we created an Innervated and Vascularized immunocompetent Tissue-Engineered Skin Tissue-Engineered Skin (IV-iTES) combining all structural and functional elements of the healthy skin.

The IV-iTES integrated human keratinocytes, fibroblasts, DCs, pseudo-capillaries and sensory nerves. Structure and cell-specific markers were thoroughly characterized. Sensory nerves could be activated in situ and subsequently released neuropeptides. When exposed to sensitizers (allergens) and control molecules, cytokines were released with a pattern that reflected the properties of the chemicals. The IViTES should allow in-depth investigations on cutaneous toxicity, angiogenesis and inflammation.

This session is a symposium on the collaboration between Japanese Society for Medical and Biological Engineering, Japan Association for Clinical Engineers, and Educational Facilities of Clinical Engineers.

I got a license of certificated clinical engineer in 1991 and got a job at a hospital in Hyogo Prefecture, Japan. Now, I have returned to home town and been working in a clinic. Where, students are accepted as a clinical engineering trainees. I also graduated the graduate school and got a Master of Science in 2018.My research is based on basic research cultivated at graduate schools and experiences in clinic.Our research team focused on the chemiluminescence generated by mixing urea and hypobromite, and attempted to make a sensor to measure the urea concentration from waste dialysate. We performed clinical trials. As a result, the correlation coefficient between the sensor and the conventional method was 0.96, which was a good result. However, continuous use caused problems such as the formation of carbonate in the reaction tank.I report the history and results of the improvement.

In hemodialysis,the relationship between backflow(BF) of the inlet chamber and hemolysis has not been fully elucidated.In this study,to examine the relationship between BF size and hemolysis,we developed a patient circuit that simulated the human body and conducted a circulation experiment using bovine blood.We have conducted this study to evaluate the effect of BF in inlet chamber on hemolysis using clinically available circuit with bovine blood.The BF was set to be 0cm,1cm,2cm and 4cm,and the red blood cell counts at 0,12,and 24 minutes were compared.At BF 0cm,the red blood cell count did not change over time.At 1,2 and 4cm of BF,there were significant differences between 0 and 12 minutes and between 0 and 24 minutes. However,there was no significant difference between 12 and 24 minutes.It was presumed that hemolysis was at risk if there was more than 1cm of BF that can be observed visually in inlet chamber.

(Purpose) The objective of the present study was to compile guidelines for the maintenance and inspection of medical devices.

(Materials and Methods) The subjects comprised devices under the Medical Care Act. Regarding the method of formulation, the guidelines related to existing training and maintenance, instruction manuals for typical products and others were analyzed. Based on these, the matters to be stated in the guidelines were extracted and the guidelines were completed after review by the academic societies.

(Results) For training, items were extracted mainly by analyzing medical accident cases. Regarding maintenance and inspections, the items stated in the existing maintenance and inspection guidelines were analyzed from the viewpoints of inspection details, procedures, and implementation frequency.

(Conclusion) It is necessary to promote the proper and safe use of medical devices by standardizing the training and maintenance of medical devices. We aim to formulate guidelines that can be implemented in clinical practice.

Transcranial magnetic stimulation (TMS) has been widely used for research and clinical applications of neurological disorders. Existing methods for designing TMS coils are either based on researchers experience or based on optimize the combination of basis functions in specific surface like plane and sphere, which cannot be used when consider the curve of head. We want to develop a numerical method capable of optimizing TMS coils shape on arbitrary surfaces. In this work, We first derive the relationship between the induced electric field and the stream function analytically. Then we solve the stream function directly from the target electric field by Tikhonov regularization. Finally, the corresponding coil shape can be obtained by drawing the contour lines of the stream function. The result of coil shape is similar to fig-8 coil on the flat plane, which illustrates the effectiveness of our method.

The multielectrode array system was used to record light-evoked action potential spikes in isolated degenerative retinal tissues to test the efficacy of photoelectric dye-coupled thin film retinal prosthesis, as a preclinical test for a medical device. Light-evoked action potential spike response was tested at first step in the isolated degenerative retinal tissue of retinal dystrophic rd1 mouse only on the multielectrode array, tested in the same retinal tissue overlain with a plain control film for light-off and light-on at second step, and tested in the same tissue overlain with a dye-coupled film at third step. The retinal tissues which showed light-evoked response at first or second step were not used for evaluation at third step. A step-by-step procedure with internal control was established to measure light-evoked action potential spikes by the multielectrode array in the isolated degenerative retinal tissue to evaluate photoelectric dye-coupled thin films.

The transcutaneous energy transmission system (TETS) is the most promising method for transmitting driving energy to a totally-implantable artificial heart (TIAH) without additional invasive procedures. In addition to a rectifier, TETS also requires a regulator to supply constant voltage to the TIAH and the implanted secondary battery in the inner circuit. This paper describes both the rectification and regulative functions, sustained on a successful long-term TIAH driving performance without circuit failure; this is accomplished by the application of a half-active rectifier (HAR) to the TETS. HAR uses metal-oxide-semiconductor field-effect transistors (MOSFET) connected in parallel on the low side of the full-bridge rectification circuit to provide a regulatory function by controlling the gate voltage of the MOSFETs. As a result, the load voltage was kept constant and the MOSFET's drain-source surge voltage was suppressed.

In this study, for the control of a small object in blood vessel by acoustic radiation force, a therapeutic ultrasonic transducer is controlled. The objective of this research is to develop a position / posture calibration control to maintain ultrasonic irradiation position accuracy and to apply to a parallel link robot. We have verified the performance of calibration control using a parallel link robot. As a result, the robot achieved positioning even when there were trackers could not be detected by the optical 3D position sensor during position control of the transducer, where the usefulness of the system was suggested. In this calibration control, the position and posture of the robot are calculated using an optical 3D position sensor and inertial sensor, and calculate the error from the command value at that moment. Then, maintaining ultrasonic irradiation position accuracy by subtracting from the command value at the next moment.

Peripheral arterial disease (PAD) has been increasing in Japan. In the case of severe PAD, surgical treatment is generally performed. Accurate grasp of the cut site is very important in securing the patient's QOL. Transcutaneous oxygen partial pressure (TcpO2) measurement is a well-established technique for existing PAD treatment, but it has some problems. We have already constructed a system to visualize the blood flow dynamics of the back and bottom of the toe. However, in a subsequent basic study of this system for PAD patients, it became clear that involuntary movements affected image processing. Therefore, the purpose of this research is to develop a blood flow dynamics visualization system that removes motion artifacts using a toe fixture and non-rigid registration. An evaluation experiment was performed with the developed system, and it was reported that the artifact on the image associated with the release of the avascularization was reduced.

Soft heating is a method of hyperthermia with few side effects. In this study, only the tumor is heated by inductively heating an implant of a thermosensitive ferromagnetic material embedded in the tumor from outside the body. We are developing a wireless temperature measurement system that detects the implant temperature wirelessly by detecting the change in implant permeability from the induced electromotive force of a pickup coil installed outside the body. However, when the distance between the excitation coil and the thermosensitive ferromagnetic material increases, the change in the magnetic field decreases, so a highly sensitive pickup coil is required. In this report, we prototyped a magnetic field application detection unit for verification that integrates an excitation coil and a pickup coil, and evaluated experimentally the validity of the coil shape and installation position.

In recent years, hyperthermia has attracted attention as a cancer treatment with few side effects. In this study, a soft heating method is used in which a temperature-sensitive magnetic implant is injected into the tumor, a high-frequency magnetic field is applied from outside the body, and the tumor is locally heated by induction heating.Previous studies have developed a constant temperature heating system that uses the change in the surrounding magnetic field due to the temperature-dependent magnetic properties of the implant to control on / off based on the induced electromotive force of the pickup coil. However, there remains a problem where the temperature of the magnetic body cannot be detected in the off state. In this report, we implemented high / low control in an automatic constant temperature heating system and evaluated its effectiveness through physical experiments.

We are investigating hyperthermia technology (soft heating method) that injects about 1 g of temperature-sensitive magnetic fine particles (implant) into the tumor and applies a high-frequency magnetic field from outside the body to locally heat the tumor. Past studies have reported a constant temperature heating system that can heat while monitoring temperature information non-invasively. However, the temperature distribution of the implant during the heating process when applying a high-frequency magnetic field was unknown.In this study, the temperature distribution inside the implant was measured with an optical fiber thermometer using the frequency and magnetic flux density of the applied magnetic field as parameters, and the heat generation unevenness was examined.

We are currently developing a research to control a thin catheter by forming acoustic radiation force. In an actual medical practice, positioning of the transducers on body surface is limited due to various shape of body surface or blood vessel on each patient. The purpose of this study to examine with various spatial placement conditions of the transducer to bend a thin catheter. Acoustic radiation force were produced to bend of the catheter in the direction perpendicular to the sound axis with various placement of transducers in line or point symmetrically. Focal position of the sound field was arranged with a step by 0.2 mm to measure the displacement of the catheter. We found that more displacement was obtained with a line symmetric arrangement rather than a point symmetric arrangement. Also, we compared the superiority of each arrangement condition through the obtained displacement.

Exposure therapy is a treatment for anxiety disorder patients. Starting with a weak stimulus might cause the symptoms return, while starting with a strong stimulus is effective but the patients come to hate the treatment. Therefore, we proposed a system that introduces VR and estimates patients' anxiety level to keep it at an appropriate level by controlling the content of VR. Firstly, we developed a method to estimate the anxiety level using physiological measures. Eight healthy male adults who gave written informed consent participated in the experiment. They were given a simulated interview in VR space presented by HMD and required to rate anxiety. Principle component analysis was applied to various sets of physiological measures and the set that showed the best explained valiance rate was selected. The possibility was suggested that its first component which can be interpreted as sympathetic activation can be used for anxiety estimation.