An SOI-Structured Piezoresistive Differential Pressure Sensor with High Performance.

This paper presents a piezoresistive differential pressure sensor based on a silicon-on-insulator (SOI) structure for low pressure detection from 0 to 30 kPa. In the design phase, the stress distribution on the sensing membrane surface is simulated, and the doping concentration and geometry of the piezoresistor are evaluated. By optimizing the process, the realization of the pressure sensing diaphragm with a controllable thickness is achieved, and good ohmic contact is ensured. To obtain higher sensitivity and high temperature stability, an SOI structure with a 1.5 µm ultra-thin monocrystalline silicon layer is used in device manufacturing. The device diaphragm size is 700 µm × 700 µm × 2.1 µm. The experimental results show that the fabricated piezoresistive pressure sensor has a high sensitivity of 2.255 mV/V/kPa and a sensing resolution of less than 100 Pa at room temperature. The sensor has a temperature coefficient of sensitivity (TCS) of -0.221 %FS/°C and a temperature coefficient of offset (TCO) of -0.209 %FS/°C at operating temperatures ranging from 20 °C to 160 °C. The reported piezoresistive microelectromechanical systems (MEMS) pressure sensors are fabricated on 8-inch wafers using standard CMOS-compatible processes, which provides a volume solution for embedded integrated precision detection applications of air pressure, offering better insights for high-temperature and miniaturized low-pressure sensor research.

Bimorph Dual-Electrode ScAlN PMUT with Two Terminal Connections.

This paper presents a novel bimorph Piezoelectric Micromachined Ultrasonic Transducer (PMUT) fabricated with 8-inch standard CMOS-compatible processes. The bimorph structure consists of two layers of 20% scandium-doped aluminum nitride (Sc0.2Al0.8N) thin films, which are sandwiched among three molybdenum (Mo) layers. All three Mo layers are segmented to form the outer ring and inner plate electrodes. Both top and bottom electrodes on the outer ring are electrically linked to the center inner plate electrodes. Likewise, the top and bottom center plate electrodes are electrically connected to the outer ring in the same fashion. This electrical configuration maximizes the effective area of the given PMUT design and improves efficiency during the electromechanical coupling process. In addition, the proposed bimorph structure further simplifies the device's electrical layout with only two-terminal connections as reported in many conventional unimorph PMUTs. The mechanical and acoustic measurements are conducted to verify the device's performance improvement. The dynamic mechanical displacement and acoustic output under a low driving voltage (1 Vpp) are more than twice that reported from conventional unimorph devices with a similar resonant frequency. Moreover, the pulse-echo experiments indicate an improved receiving voltage of 10 mV in comparison with the unimorph counterpart (4.8 mV). The validation of device advancement in the electromechanical coupling effect by using highly doped ScAlN thin film, the realization of the proposed bimorph PMUT on an 8-inch wafer paves the path to production of next generation, high-performance piezoelectric MEMS.

Development of MEMS Airflow Volumetric Flow Sensing System with Single Piezoelectric Micromachined Ultrasonic Transducer (PMUT) Array.

Compared to conventional ultrasonic flowmeters using multiple transducers, this paper reports, for the first time, an airflow volumetric flowmeter using a signal PMUT array to measure the flow rate in a rectangular pipe. The PMUT around 200 kHz is selected to fit the system requirements. All PMUT elements on this single array are then electrically grouped into transmitter and receiver. In order to minimize the crosstalk signal between transmitter and receiver, a phase shift signal is applied at the transmitter to reduce the amplitude of the crosstalk signal by 87.8%, hence, the resultant high sensing resolution. Based on the analog signal extracted from the single PMUT array, a complete flow sensing system is built by using the cross-correlation method and cosine interpolation, whereby the change in flow rate is reflected by the time of flight difference (dTof) recorded at the receiver. Meanwhile, the acoustic path self-calibration is realized by using multiple echoes. Compared with the previously reported MEMS flowmeters with dual or multiple PMUT devices, this paper proposes a single PMUT array flow sensing system, which is able to measure the flow rate changes up to 4 m3/h. With the implementation of a single device, the problem of ultrasound device/reflector misalignment during system setup is completely eradicated.

AlScN Film Based Piezoelectric Micromechanical Ultrasonic Transducer for an Extended Long-Range Detection.

Piezoelectric micromachined ultrasonic transducers (PMUTs) have been widely applied in distance sensing. However, the sensing distance of currently reported miniaturized ultrasonic sensors (e.g., PMUTs or CMUT) is still limited up to a certain range (e.g., ≤5 m) compared to conventional bulk ultrasonic devices. This paper reports a PMUT array design using scandium-doped aluminum nitride (AlScN) as its piezoelectric layer for an extended long-range detection purpose. To minimize air attenuation, our device is resonating at 66 kHz for a high receive sensitivity of 5.7 mV/Pa. The proposed PMUT array can generate a sound pressure level (SPL) as high as 120 dB at a distance of 10 cm without beam forming. This PMUT design is catered for a pin-to-pin replacement of the current commercial bulk ultrasonic ranging sensor and works directly with the conventional range finding system (e.g., TI PGA460). In comparison with the common bulk transducer, the size of our device is 80% smaller. With the identical ranging detection setup, the proposed PMUT array improves the system SNR by more than 5 dB even at a distance as far as 6.8 m. The result of extended sensing distance validates our miniaturized PMUT array as the optimized candidate for most ultrasonic ranging applications. With the progressive development of piezoelectric MEMS, we believe that the PMUT technology could be a game changer in future long-range sensing applications.

Propofol induces the apoptosis of neural stem cells via microRNA-9-5p / chemokine CXC receptor 4 signaling pathway.

Recent studies suggested that propofol, one of the most widely used anesthetics, may cause neurotoxicity in the developing brain, leading to cognitive deficits in adults. However, the underlying mechanisms remain unclear. In this study, we aimed to evaluate the mechanisms of propofol neurotoxicity in the neural stem cells (NSCs). The mRNA and protein expression levels of microRNA-9-5p (miR-9-5p) and chemokine CXC receptor 4 (CXCR4) were determined by quantitative reverse transcription-polymerase chain reaction and Western blotting analyses. Cell viability and apoptosis were evaluated using the cell counting kit-8 and Hoechst staining kits. The levels of apoptosis-related proteins B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 were detected by Western blotting analysis. These results confirmed that propofol activated cell apoptosis in a dose-dependent manner. A significant increase in the miR-9-5p and CXCR4 expression was observed in the propofol-treated cells. The overexpression of miR-9-5p induced apoptosis in NSCs, accompanied by elevated apoptosis-related protein activity. Furthermore, mitigated CXCR4 expression reduced propofol-induced cell apoptosis. We conclude that propofol induces cell death in NSCs, and overexpression of miR-9-5p/CXCR4 contributes to propofol-induced cell apoptosis, which might be a target for developing novel strategies to treat propofol neurotoxicity.

The mechanism of the premetastatic niche facilitating colorectal cancer liver metastasis generated from myeloid-derived suppressor cells induced by the S1PR1-STAT3 signaling pathway.

The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1-STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14+HLA-DR-/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1-STAT3-IL-6-MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1-STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

Acute and sub-chronic toxicity studies of Danshen injection in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge named Danshen in China has been used for hundreds of years in both China and other countries. Danshen injection made from the aqueous extract of Danshen which is widely adopted in China is one of the traditional Chinese medicine injections for preventing and treating cardiovascular diseases in most of the time. The present study was carried out on re-evaluating the safety of Danshen injection by determining toxicity after acute and sub-chronic administration in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: In acute toxicity study, rats (10 males and 10 females) were intravenously administered Danshen injection dose of 32g/kg body weight, two times in one day. General behavior, adverse effects and mortality were recorded for up to 14days post treatment. In the sub-chronic study, Danshen injection was given intravenously at the doses of 0, 1.92, 5.76, and 19.20g/kg per day (n=15/group each sex) for 13weeks to rats. Animal body weight and food intakes were observed weekly. Hematological, biochemical parameters and organ weight were determined in all animals at the end of the 13-week administration and 2-week recovery. However, histological examinations were carried out in the control and high-dose groups only. RESULTS: In acute study, the sign of struggling was observed in some animals at the moment of intravenous administration. No deaths and other signs of toxicity occurred in any of the animals tested during the 14days of the study. In sub-chronic study, Danshen injection did not result to death, adverse effects or dose-dependent changes in food consumption, but had an effect on body weight gain. Some statistically significant differences were observed in hematological and biochemical parameters, as well as in some organ weights of both male and female rats treated with Danshen injection. In these changes, the significant decrease in triglycerides and increase in total bilirubin were considered related to treatment, indicating the lipid-modulating activity of Danshen. Histopathological examinations of the injection site showed that Danshen injection could cause dose-dependent focal inflammation. There was no abnormality of other organs noted in both gross and histopathological examinations. CONCLUSIONS: The results showed that acute or sub-chronic administration of Danshen injection was low or non-toxic in male and female rats, and the no-observed-adverse-effect-level for sub-chronic administration of Danshen injection dose was 5.76g/kg bw/day, which was suggested that it was safe in clinical use.