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Respiration and heartbeat are among the important vital signs of living beings. Taking advantage of the physical attachment of lung and heart, measurements of both can be performed simultaneously using airflow rate microsensors to measure the respiration airflow. For such airflow rate sensors, the packaging is crucial to define and encapsulate the airflow region. In this study, we propose a facile packaging technique for flexible airflow rate microsensor. The thermal calorimetric sensing structure was fabricated through a standard microfabrication technology on a thin polyimide film. The film was packaged at the center of a resin tube utilizing its buckling. We also proposed an approach to improve the time response by limiting the thermal capacity around the sensing structure through the implementation of a thin substrate for the sensing structure supported by a thicker film. The strategy successfully improved both the time response and sensitivity of the airflow rate sensor. Finally, the utilization of the sensor for simultaneous respiration and heartbeat measurement was demonstrated through an animal experiment using a small animal, namely rat.

We propose a sensor-probe system for evaluating local airway resistance in the lungs. The system consists of a micro-machined thermal-flow sensor, based on the hot-wire airflow-meter principle, fabricated on a flexible substrate consisting of Cu foil and polyimide film and a commercially available Si pressure sensor. We inserted the system into a tube with a 5.0-mm inner diameter to evaluate its detection properties under a steady-flow of up to 6.0 L/m. The flow velocity vs. sensor output and pressure vs. tube length were successfully obtained. We then applied the system for reciprocating airflow measurement. A flow of 30 cc at 0.5 Hz generated with an artificial ventilator was used to imitate the breathing of a small animal, and we confirmed that the system successfully detected both flow and pressure change generated in the tube.

Acute rejection is still a major problem in transplantation and one of the most important causes of late graft loss. Cyclosporine and tacrolimus are widely used for suppression of T cell function to avoid graft rejection, but long-term use of these compounds is associated with serious toxicities. Quercetin, a flavonoid found in fruits and vegetables, has been demonstrated to exhibit cytoprotective effects through the induction of heme oxygenase (HO) -1, an enzyme involved in heme catabolism. We hypothesized that quercetin induces HO-1 in T cells and suppresses T cell function via HO-1. In the present study, we showed that quercetin suppressed the A23187-mediated expression of interleukin (IL) -2 in T cells. Mouse splenocytes, enriched T cells, and EL4 cells, a mouse T cell line, were treated with quercetin, and then stimulated with A23187, a calcium ionophore, concanavalin A, or anti-CD3ε and anti-CD28 antibodies. Cell proliferation, expression of IL-2, calcium mobilization, apoptosis, cell cycle, and phosphorylation of extracellular signal-regulated kinase (ERK) were investigated. Quercetin induced HO-1, and this induction of HO-1 was implicated in the suppression of IL-2 production. Furthermore, the induction of HO-1 by quercetin suppressed the influx of calcium ions, a known trigger of IL-2 production. Additionally, quercetin suppressed T cell proliferation through promotion of cell cycle arrest via HO-1 induction, but quercetin did not induce apoptosis. To investigate the role of the signal transduction pathway in quercetin’s effect on cell proliferation, we evaluated the phosphorylation of ERK in T cells. Quercetin suppressed the A23187-mediated stimulation of ERK, an effect that was mediated through HO-1. These results suggested that HO-1 is involved in the suppressive effects of quercetin on T cell activation and proliferation. Our findings indicate that the quercetin may be a promising candidate for inducing HO-1 in T cells, thereby facilitating immunosuppressive effects.

We developed a respiratory monitoring system to evaluate elasticity on the lungs of small animals by the positive-pressure airflow under artificial ventilation during experiments. The system consists of a tube-type thermal flow sensor fabricated using microelectromechanical systems (MEMS) technology and commercially available Si-MEMS pressure sensors. We first used a small spherical balloon having an inner volume of 0.68 cc as a simulated lung. We evaluated the balloon elasticity from the supplied flow volume and pressure inside the balloon and confirmed that our system can detect balloon elasticity from the gradient under both static and cyclic airflow. We evaluated our system in terms of the lung elasticity of a rat and obtained a flow volume vs. pressure curve showing the lung elasticity under artificial ventilation. The changes in the flow rate and pressure waveforms due to airway contraction with drug administration were detected with our system in real time.

A catheter sensor system composed of a tube flow sensor with a medical basket forceps and an optical fiberscope was systemized for in-situ measurements in the airway in the lung system. The tube flow sensor was produced by assembling the sensor film containing two heaters onto the tube surface, and the basket forceps was installed into the inside space of the tube sensor. The assembled tube flow sensor with the basket forceps was inserted into the tube and was fixed at the center of the tube by expanding the basket. The flow detection characteristics of the tube flow sensor were experimentally evaluated. A calibration equation based on King’s law was derived from the sensor output vs. flow velocity curve, and a sufficiently short response time of 60 ms was obtained for the breathing measurements in a rabbit and a person. Finally, the tube flow sensor with the basket forceps and the optical fiberscope was systemized into a single tube with the diameter of 5.0 mm for in-situ measurements in the airway. The developed system successfully detected both a breathing airflow waveform and an optical image inside the airway in the rabbit.

In this work, we developed a MEMS flow sensor for application to a drip infusion system. The MEMS sensor is composed of a silicone rubber layer, a film sensor with a flow rate measurement element consisting of a metal heater and thermistors formed on a thin polyimide film, and a PDMS layer with a flow channel that utilizes a plastic plate as a substrate. In the drip infusion system, the flow sensor needs to have high sensitivity in a low flow rate range under a low driving temperature condition in order to achieve high-precision drug delivery. Therefore, we utilized the calorimetric method as a flow rate measurement principle to improve the sensor sensitivity and set the driving condition of the sensor to 40 °C or less to prevent deterioration of the infusion drug. Experiments under these conditions showed that our flow sensor had high sensitivity in the low flow rate range of 5.0 g/min or less. We also evaluated the flow rate detection function using various liquids having the same properties as the drip infusion solution in the driving temperature of 40 °C or less and found that the flow sensor could sufficiently measure each solution within the set flow rate range.

It is important to know the drug level in the target tissue to determine its dose. Some methods rely on blood levels of a drug to estimate its concentration in the tissues, which can be inaccurate. We thought that drug levels in exhaled breath aerosol (EBA) to give a more accurate value of the level of a test drug in the lung. Rats were intravenously injected with the bronchodilator theophylline and exhaled breath was collected up to 10–20 min after administration. Immediately after breath collection, lung, liver, kidney, and blood were collected and the pharmacokinetics were examined using these samples. Awake free-moving rats were used to efficiently collect exhaled breath from rats with low tidal volume. The amount of exhaled breath of rats was estimated by the amount of exhaled water vapor, and the drug concentration in exhaled breath sample was expressed by the amount of water vapor as the denominator. By using the active sampling method in which the adsorbent is sucked by a pump, theophylline in rat exhaled breath could be measured accurately. When the correlation of theophylline concentration in each sample was examined, a high correlation (r 2 = 0.74) was found only in exhaled breath and lung tissue. EBA was considered better than blood in pharmacokinetic analysis of lung tissue.

Mutant KRAS, the most frequently occurring (~30%) driver oncogene in lung adenocarcinoma, induces normal epithelial cells to undergo senescence. This phenomenon, called “oncogene-induced senescence (OIS)”, prevents mutant KRAS-induced malignant transformation. We have previously reported that mutant KRAS(V12) induces OIS in a subset of normal human bronchial epithelial cell line immortalized with hTERT and Cdk4. Understanding the mechanism and efficacy of this important cancer prevention mechanism is a key knowledge gap. Therefore, this study investigates mutant KRAS(V12)-induced OIS in upregulated telomerase combined with the p16/RB pathway inactivation in normal bronchial epithelial cells. The normal (non-transformed and non-tumorigenic) human bronchial epithelial cell line HBEC3 (also called “HBEC3KT”), immortalized with hTERT (“T”) and Cdk4 (“K”), was used in this study. HBEC3 that expressed mutant KRAS(V12) in a doxycycline-regulated manner was established (designated as HBEC3-RIN2). Controlled induction of mutant KRAS(V12) expression induced partial epithelial-to-mesenchymal transition in HBEC3-RIN2 cells, which was associated with upregulated expression of ZEB1 and SNAIL. Mutant KRAS(V12) caused the majority of HBEC3-RIN2 to undergo morphological changes; suggestive of senescence, which was associated with enhanced autophagic flux. Upon mutant KRAS(V12) expression, only a small HBEC3-RIN2 cell subset underwent senescence, as assessed by a senescence-associated β-galactosidase staining (SA-βG) method. Furthermore, mutant KRAS(V12) enhanced cell growth, evaluated by colorimetric proliferation assay, and liquid and soft agar colony formation assays, partially through increased phosphorylated AKT and ERK expression but did not affect cell division, or cell cycle status. Intriguingly, mutant KRAS(V12) reduced p53 protein expression but increased p21 protein expression by prolonging its half-life. These results indicate that an hTERT/Cdk4 -immortalized normal bronchial epithelial cell line is partially resistant to mutant KRAS(V12)-induced senescence. This suggests that OIS does not efficiently suppress KRAS(V12)-induced transformation in the context of the simultaneous occurrence of telomerase upregulation and inactivation of the p16/Rb pathway.

Multi-vital signs detection; respiration, heart rate, and body temperature from respiration airflow at the mouth was proposed, and three sensors patterns (flow-rate, - direction, and -temperature sensors) were formed on a single MEMS sensor. The small-sized tube type flow sensor was designed and fabricated to apply it the animal experiment, and its detection characteristics were experimentally evaluated. The flow rate sensor output followed the King's equation, and the response time of 50 ms was obtained to confirm the following oscillating breathing airflow measurement. Then, we confirmed that the fabricated sensor can measure the airflow whose temperature changes periodically. Finally, we conducted an animal experiment using rats, and confirmed that the fabricated sensor can measure three vital signs of respiration, heart rate, and body temperature from respiration.

We propose an easy-to-use energy-less respiration monitoring device for monitoring the breathing flow using a thermo-sensitive film. Thermo-sensitive film less than 0.01 mm thick with thermo-sensitive ink and a base film were wrapped over the aperture and partially produced in the tube for monitoring the breathing status. The aperture used as the respiration monitoring area, also worked as thermal isolation to shorten the response time and to decrease thermal capacity in the monitoring area. The response time was investigated using a response evaluation device (designed and produced using MEMS technology) to follow the temperature change with the breathing cycle of 0.3 Hz. The response time depended on the thickness of both the ink and the base film and decreased with the decrease of the thickness due to thermal capacity reduction. The obtained minimum response time was 373 ms when the ink thickness was 6.8 μm and the base film thickness was less than 5.0 μm. The color of the ink at the breathing monitoring area formed on the aperture successfully changed from blue to transparent according to the temperature change of the airflow.

Continuously monitoring a patient body condition during large scale disasters requires vital information to be acquired quickly and easily to aid medical professionals. Breathing airflow, especially exhaled airflow, contains not only respiration but also body temperature information. Thus, a body temperature measurement method using exhaled airflow was proposed, and a temperature sensor was implemented into a thermal-type breathing airflow sensor to detect both respiration and body temperature information from breathing airflow alone. Both sensors were designed and fabricated by MEMS technologies. The temperature sensor operated with an input power of less than 0.5 mW to prevent self-heating, and we confirmed it can detect the air temperature with an accuracy of less than 1.0 °C under different temperature airflow conditions. The effects of the thermal airflow sensor on temperature measurements were also experimentally evaluated, and we concluded that the developed sensor can measure the airflow temperature with an accuracy of less than 0.5 °C. Finally, the developed sensors successfully detected periodical temperature changes in the airflow, mimicking human breathing.

Optical coherence tomography (OCT) is a noninvasive cross-sectional imaging technique with micrometer resolution. The theoretical axial resolution is determined by the center wavelength and bandwidth of the light source, and the wider the bandwidth, the higher the axial resolution. The characteristics of OCT imaging depend on the optical wavelength used. In this paper, we investigated the wavelength dependence of ultrahigh-resolution (UHR) OCT using a supercontinuum for biomedical imaging. Wideband, high-power, low-noise supercontinua (SC) were generated at λ = 0.8, 1.1, 1.3, and 1.7 μ m based on ultrashort pulses and nonlinear fibers. The wavelength dependence of OCT imaging was examined quantitatively using biological phantoms. Ultrahigh-resolution imaging of a rat lung was demonstrated with λ = 0.8–1.0 μ m UHR-OCT. The variation of alveolar volume was estimated using three-dimensional image analysis. Finally, UHR-spectral domain-OCT and optical coherence microscopy at 1.7 μ m were developed, and high-resolution and high-penetration imaging of turbid tissue, especially mouse brain, was demonstrated.

Optical coherence tomography (OCT) is a non-invasive cross-sectional imaging technique with micrometer resolution. OCT is useful, non-invasive imaging technique of the internal structure, and it has been applied in many fields, especially medicine and industry. The theoretical axial resolution is determined by the center wavelength and bandwidth of the light source, and the wider the bandwidth is, the higher the axial resolution is. Supercontinuum is the high-power, ultrawideband light source. We have been investigating ultrahigh-resolution (UHR)-OCT using supercontinuum. The characteristics of OCT imaging depend on the optical wavelength used. In this talk, we report our recent work of the wavelength dependence of UHR-OCT using a supercontinuum for biomedical imaging. In order to investigate the wavelength dependence of UHR-OCT, the wideband, high-power, low-noise supercontinua were generated at wavelengths of 0.8, 1.1, 1.3, and 1.7 um based on ultrashort pulses and nonlinear fibers. The wavelength dependence of OCT imaging was examined quantitatively using biological phantoms. Ultrahigh-resolution imaging of a rat lung was demonstrated with wavelengths of 0.8 – 1.0 um UHR-OCT. The variation of alveolar volume was estimated using 3D image analysis. We also developed UHR-spectral domain-OCT and optical coherence microscopy (OCM) at 1.7 um. The high-resolution and high-penetration imaging of turbid tissue, especially mouse brain, was demonstrated. The wavelength dependence of OCM was also discussed in terms of mouse brain imaging.

A micro-machined flow sensor and a stent were integrated to enable evaluation of the in-situ breathing properties in the air passage of experimental animals. A tube flow sensor that operates on the thermal principle was fabricated using micro-electro-mechanical systems technology, and a newly designed stent structure was fabricated using photolithography and wet etching processes. The fabricated flow sensor and stent were integrated via connection areas formed on both elements. The developed stent flow sensor device was positioned at the center of the tube's cross-section by expanding the stent. The flow rate detection property was evaluated to obtain calibration curves for use in converting the sensor output value into a flow rate waveform. Testing using an artificial ventilator demonstrated that the stent flow sensor device can be placed in the air passage of small animals to detect the breathing airflow directly. A potential application is the development of new drugs.

We preivously developed a catheter type flow sensor for measuring breathing and heartbeat information from breathing at the mouth [Hasegawa et al. J Micromech Microeng 27(12): 125016, (2017); Kawaoka et al. Tech. Dig. IEEE Micro Electro Mechanical Systems Conference 2016, pp 359–362]. In this study, we redesigned and developed the new sensor configuraiton for the catheter flow sensor to downsize and improve the sensor characteristics. The previous flow sensor consists of two pairs of a heater and a temperature compensation sensor for flow rate detection. The two heaters also functioned not only for flow rate detection but also for flow direction detection. The two temperature compensation sensors had a large footprint and corresponded to each heater. Therefore, the sensor occupied a large area, and it was necessary to match the heater characteristics for flow rate detection. The newly designed sensor is composed of a set of a heater and a temperature compensation sensor and two flow direction sensors. By providing the new flow direction sensors, the number of temperature compensation sensors with a large footprint was reduced to one. Thus, the area of the new sensor design was 15.0 mm2, which was reduced to 54.5% of the 27.0 mm2 of the previous sensor area by providing the flow direction sensors. Then, the new catheter type flow sensor was fabricated, and the flow characteristics for measuring breathing funciton were evaluated. Finally, we applied the catheter type flow sensor to an animal experiment using a rat, and it could evaluate the flow rate characteristics of the rat’s breathing as a reciprocating flow including flow direction. Moreover, the obtained breathing characteristics were within the range of the physiological values of rats.

A micro-electro-mechanical systems flow sensor was integrated onto an optical fiberscope to enable in situ breathing and surface image evaluations in small airways. The tube flow sensor was developed to be easily attached to an optical fiberscope. Firstly, two heaters working as flow rate sensors were formed on thin film by using a lift-off process. Then the fabricated film sensor was assembled onto the outer tube surface by film transfer technology. The flow rate vs. sensor output characteristics under both the forward and backward flow conditions were confirmed to be coincident. Thanks to thermal capacity reduction by 1.0 μm-thickness film substrate and thermal isolation by cavity formation around the heaters, a short response time of less than 20 ms was obtained. This was sufficient to follow the temporal airflow rate change during breathing. The fabricated tube flow sensor was attached to the outside of a fiberscope 1.6 mm in diameter, and it was inserted into a tube that was connected to the airway of a rat. An optical image of the rat was captured, and its breathing airflow rate was successfully detected.

Since their early stages of development, micro-electro-mechanical systems (MEMS) have shown potential for breakthroughs in the fabrication of medical tools. The miniaturization of various devices using MEMS technology has enabled minimally invasive treatments and in situ measurements. In this paper, we introduce two advancements in MEMS applications in the medical field: (1) microneedle devices for brain activity evaluation, a transdermal drug delivery system, and biological fluid sampling; and (2) miniaturized MEMS sensors for monitoring the conditions inside blood vessels and respiratory organs. In addition, we provide a summary of MEMS sensors used in developing new drugs, detecting vital signs, and other applications.

We inserted a tubular flow sensor incorporating micro-electro-mechanical systems technologies directly into the rat airway and analyzed the airflow waveforms obtained under different depths of anaesthesia conditions by using discrete Fourier transformation (DFT) to evaluate the heartbeat frequency. The electrocardiogram (ECG) signal was used as the reference heartbeat frequency. The calibration curve of the flow sensor used to measure the oscillating airflow in the rat airway was determined on the basis of King’s law. The airflow waveform at the rat airway caused by only the heartbeat was measured by applying deep anaesthesia; the waveform frequency coincided with the simultaneously measured ECG signal frequency. DFT analysis of the airflow signals measured under deep and shallow anaesthesia conditions verified the fundamental heartbeat frequency values. The airflow components related to heartbeat motion were successfully extracted by using the heartbeat frequency spectrum. The respiration and heartbeat signals were thus successfully detected.

We previously proposed a basket-forceps-type flow sensor, in which a flexible thermal flow sensor is mounted onto basket forceps to fix the flow sensor onto the inside surface of the airway. The basket-forceps-type flow sensor has an asymmetrical structure to prevent reciprocating airflow; thus, we investigated the characteristics of the basket-forceps-type flow sensor under both expired- and inspired-airflow conditions in this study. The thermal flow sensor was fabricated on a flexible polyimide film and mounted onto a guide tube of a basket-forceps. Two heaters and their electrical wiring patterns were designed to produce symmetric heat distribution over the heaters. The effects of the basket structure and guide tube on flow-rate measurement were experimentally evaluated, and it was confirmed that they did not affect sensor output. Conversely, sensor output decreased with the increase in tube diameter due to the reduction in the average flow velocity with the diameter increase. Thus, we carried out a procedure to construct a calibration curve under an arbitrary tube diameter. Finally, we applied the basket-forceps-type flow sensor in an animal experiment in which it successfully detected the breathing properties in the airway of a rat.

A novel catheter sensor system was developed for performing in-situ breathing measurements and optical imaging in the bronchus of the lung. A tube flow sensor was fabricated by attaching sensor film to a tube with the diameter of 2.0 mm. Medical basket forceps were inserted into the space inside the tube flow sensor in order to fix its position in the airway. The flow sensor and optical fiberscope were installed together in a tube 5.0 mm in diameter. The resulting catheter sensor system was inserted into a rabbit airway by using an optical fiberscope, and it could directly and simultaneously measure the breathing airflow volume and take images of the inside surface of the rabbit airway.

A MEMS flow sensor, an electrical wiring, and a flow tube structure were integrated onto the same substrate, for the first time. A Cu on polyimide (COP) was used as the sensor substrate. First, both sensor devices composed of a heater working as flow velocity sensor and a temperature sensor, and electrical wiring were fabricated in the same substrate. The signal lines in the sensor device were automatically connected to the electrical wiring formed into the Cu layer during the fabrication to eliminate an electrical bonding process. Finally, the tube structure was successfully integrated with the same substrate of the sensor device and the wiring to deform a part of COP substrate plastically. Flow detection and response time of fabricated flow sensor were evaluated as the basic characteristics. Besides, it was applied in the breathing flow measurements in rat, as one of the applications, and the breathing airflow at the rat was directly detected.

Malaria is caused by Plasmodium parasites and is one of the most life-threatening infectious diseases in humans. Infection can result in severe complications such as cerebral malaria, acute lung injury/acute respiratory distress syndrome, and acute renal injury. These complications are mainly caused by P. falciparum infection and are major causes of death associated with malaria. There are a few species of rodent-infective malaria parasites, and mice infected with such parasites are now widely used for screening candidate drugs and vaccines and for studying host immune responses and pathogenesis associated with disease-related complications. We found that mice of the NC/Jic strain infected with rodent malarial parasites exhibit distinctive disease-related complications such as cerebral malaria and nephrotic syndrome, in addition to a rapid increase in parasitemia. Here, we focus on the analysis of host genetic factors that affect malarial pathogenesis and describe the characteristic features, utility, and future prospects for exploitation of the NC/Jic strain as a novel mouse model for malaria research.

We developed a stent flow sensor using micro-electromechanical systems (MEMS) technology in order to measure airflow in the airways of laboratory animals. An airflow waveform contains a respiration signal produced by lung motion and heartbeats as these functions are physically connected. This enables both respiration and heart functions to be evaluated under unrestrained and unanesthetized conditions during drug development. Using MEMS technology, we fabricated a tube flow sensor based on a thermal principle, and the stent structure was produced by photolithography and wet etching. The fabricated flow sensor and stent were integrated via a connection area on both elements. In the proof-of-concept trial, we verified that the flow sensor was placed in the center of the tube by expanding the stent. We evaluated the flow detection characteristics, sensor output vs flow rate and sensor response and used the developed stent flow sensor to measure the airflow in the airway of a rat. The respiration and heartbeat signals were successfully identified from the airflow waveform by applying Fourier transform analysis.

An implantable catheter flow sensor with legs for measuring the breathing characteristics of disease-model animals was developed. The unique feature of this sensor is the use of legs to fix the sensor to the inside wall surface of the air passage without preventing ciliary motion. Differently shaped legs were fabricated by application of a heat shrinkable tube. Prototype sensors was inserted into tubes with inner diameters ranging from 2.4 to 2.7 mm and successfully anchored to the inside surface by the legs. An evaluation of the relationship between the sensor output and the flow rate demonstrated that the sensor output against the flow rate obeyed King's law. The sensor output variation with different inner tube diameters was suppressed to less than 3 %. The developed catheter flow sensor was applied to the breathing measurements in the rat and the rabbit. The breathing waveform obtained from the flow sensor in the rat coincidented to the mechanism of breathing. The sensor was implated into the rabbit bronchus by using a fiberscope, and the breathing characteristics in the bronchus 3 days after implant were successfully measured.

The possibility of using exhaled breath as a substitute for blood/plasma in areas of therapeutic drug monitoring was investigated. Theophylline was used as a model chemical of non-volatile drugs and the adsorbents suitable for drug capture from exhaled breath were studied. Two macro-porous adsorbents with different monomer compositions were prepared by suspension copolymerization. The capture properties of the synthesized adsorbents and two conventional gas adsorbents packed in a cartridge were evaluated by both aerosol generation and rat expiration. The efficiency of drug capture did not improve by decreasing the pore size and by increasing the specific surface area. A hydrophilic region was found to be necessary for holding the aerosol particles on the adsorbent surface, but a hydrophobic region is also necessary for the adsorption of theophylline. The materials were applied to the intravenous bolus experiment of rats. The amount of theophylline collected from exhaled breath was in the range of 0–0.02 ng min−1, and it varied similarly to the concentration in blood, which was in the range of 0–37 μg mL−1.

Respiratory viral infections that cause chronic airway and lung disease can result in the activation of the innate immune response. Alveolar macrophages (AMs), one of the first lines of defense in the lung, are abundantly located in alveoli and the respiratory tract. Flavonoids found in fruits and vegetables exhibit cytoprotective effects on various cell types. In this study, we investigated the effect of quercetin on activation of AMs that had been exposed to imiquimod, a ligand of Toll-like receptor (TLR) 7. In both a mouse AM cell line (AMJ2-C11 cells) and mouse bronchoalveolar fluid cells, we demonstrated that quercetin attenuated TLR7-induced the expression of TNF-α and IL-6. In AMJ2-C11 cells, quercetin also attenuated the TLR7-induced CD40 expression; attenuated the translocation of p65; induced translocation of Nrf2 from cytosol to nucleus; and induced heme oxygenase (HO)-1 expression. Notably, tin protoporphyrin IX (SnPP), an inhibitor of HO-1, also attenuated TLR7-induced transcription of the TNF-α and IL-6 genes, suggesting that the effect of quercetin is mediated by HO-1. These results suggest that dietary supplementation with quercetin may have efficacy in the treatment of respiratory viral infection.

We designed and fabricated a tube-type thermal flow sensor for fabricating an adult-sized tracheal intubation tube device intended for clinical practice. The sensor film was packaged into the inside surface of the tube by interface tension and parylene coating, and a flow sensor for an adult-sized tracheal intubation tube was successfully produced. We experimentally investigated flow rate detection and response time and found that the flow sensor fitted King’s model in terms of flow rate detection and has a sufficiently short response time of 59 ms. Thus, we concluded that the developed sensor will be applicable to measuring breathing characteristics of adults in the near future. Finally, the developed sensor was assembled into a tracheal intubation tube actually used in medical treatment.

We attempted to develop different sized catheter flow sensors for evaluating breathing characteristics at different levels of the tracheobronchial airway in a lung system. Two catheter flow sensors with 1.8 and 3.5 mm outer diameters were designed for measuring breathing characteristics in bronchus- and bronchiole- regions in the lung system, respectively. They were fabricated by using photolithography and heat shrinkable tube packaging processes. We experimentally investigated the fundamental sensor characteristic and found that the sensor output depended on the mean flow velocity. The developed catheter flow sensors also successfully detected the oscillating airflow produced by an artificial ventilator.

This paper presents a novel tube flow sensor to measure airflow in mouths for detecting respiration and heartbeat signals of premature babies in incubators. A flow rate sensor with temperature compensation and a flow direction sensor were combined to decrease their footprint on a sensor film. The fabricated sensor film was assembled onto the inside surface of the tube, and its detection properties were investigated. The sensor output in the flow rate sensor obeyed King’s model. The value of output in the flow-direction sensor was changed in accordance with the change of the airflow direction.

We challenged ourselves to integrate a flow sensor into an optical fiberscope for in-situ breathing and surface image evaluations in small airways. Film transfer technology was applied to attach the flow sensor onto a curved tube surface. A single wrapping process that used double-sided tape was introduced, and the miniaturized tube-type flow sensor was developed to be easily attached to the outside of the optical fiberscope. Two tubes with inner diameters of 1.4 and 2.0 mm, respectively, were used to correspond to the variations sized fiberscopes. The fabricated tube-type flow sensor was attached onto a SUS rod with the same diameter as that of the target fiberscope. Two sensor characteristics were experimentally evaluated, and the results confirmed that the developed sensor system can be applied to breathing and image evaluations in small airways.

A micro-electro-mechanical systems catheter flow sensor was integrated into the tracheal intubation tube system to prevent the insertion of the tube into the esophagus. A temperature sensing mechanism was integrated into the catheter flow sensor to compensate for the temperature change in air during flow-rate measurement, and the sensor was placed on the inside the slip joint by using an adapter produced using a molding process. The relationship between the sensor output and flow rate was evaluated, and closely matched sensor outputs for both the forward and backward flows were obtained. The tracheal tube in the modified system was inserted into the air passage of a rabbit, and the air flow passing through the tube was directly measured using the integrated catheter flow sensor in real time. By adding the temperature compensation mechanism, the volumes of the expired- and inspired-air almost matched. We believe that a doctor will easily be able to evaluate whether the tube is inserted into the bronchi or the esophagus when using the modified system.