Poster Session



Poster Section II – Biomedical Photonics, Clinical Engineering, Medical Electronics, Nanomedicine, Neuroengineering

Dec. 1, 2018 15:30 PM - 16:30 PM


Shu-Jen Chiang, Ting-Hsuan Wu, Shean-Jen Chen, Ji Wang, Shih-Chi Chen, Pei-Hsing Huang and Chen Yuan Dong

Understanding how neuro-circuitry functions represents one of the final frontiers of human scientific endeavors. It is well known that the disruption in connections among neurons can contribute to a number of diseases, many of which cannot be cured with current medical technologies. Therefore, obtaining a road map of the neuronal network in normal and diseased brains represents a significant step in understanding brain and treating its diseases. In this work, we present our effort in obtaining high content, three-dimensional volumetric imaging of the brain by serial imaging and sectioning histological spec-imens. We report our progress in combining multiphoton microscopy with a high-precision, oscillating-blade microtome in obtaining volumetric images of the brain in model animals at sub-micron resolution.


Cheng An Lin and Tzu-Yin Hou

Lung Adenocarcinoma (LA), the one of the high-risk cancer diseases, is hard to do the detection and recognition. More and more clinical reports have revealed the abnormality expression of microRNA within extracellular vesicles (EV-microRNA) in most LA patients. However, the traditional methods of microRNA detection need high costs as well as the manpower, resulting in the hardness of regular analysis. From our interdisciplinary teamwork, we propose to develop more efficient detection system for the EVs-microRNA within the LA patents. In this project (sub-project II), we propose an innovative idea of surface-enhanced total internal reflective fluorescence(SE-TIRF) technology for EVs detections.


Jhen-Yang Syu, Yen-Lin Sung, Ting-Tse Lin and Shien-Fong Lin

Abstract— Background: Hypertension is a multifactorial disease involving a major contribution for cardiovascular events. Valsartan is a common prescription for hypertension, and approved to reduce mortality in patients with systolic heart failure when combined with sacubitril (EntrestoⓇ). There is little data regarding the impact of valsartan/sacubitril on cardiac electrophysiology. We hypothesized that this drug could improve arrhythmogenicity in spontaneously hypertensive rats (SHR). Methods: We treated WKY rats as control and fed both groups with placebo, and valsartan/sacubitril respectively for 8 weeks (WKY, WKY-valsartan/sacubitril, SHR, and SHR-valsartan/sacubitril; each n = 6). The optical mapping was applied to measure ventricular electrophysiology, including APD70 ,diastolic interval (DI) and the maximum slope of APD-DI plot. Results: In SHR group, APD70 was prolonged in subjects fed with valsartan/sacubitril when compared with placebo (SHR vs. vs. SHR- valsartan/sacubitril, 105±30.41 vs. 39±8.18, p=0.022) . WKY group showed no difference among treatment. The maximum slope of SHR fed with placebo was higher than those fed with valsartan and valsartan/sacubitril (SHR vs. SHR-valsartan/sacubitril, 1.19±0.33 vs. 0.07±0.02, p=0.004). Likewise, there was no difference in the WKY groups. Conclusions: According to results, valsartan/sacubitril could reduce APD and improved arrhythmogenecity caused by hypertension and cardiac hypertrophy in the rat model.


Tsai, Chih-I and Tseng, Chui-Shen

Osteoarthritis (OA) is a type of arthritis with disease of knee which commonly affects elder peoples. Through clinical observation, the researchers found that many people with osteoarthritis had sagging cheeks. We used Platelet-rich plasma injection and acupuncture to cure people with osteoarthritis and further lifted their sagging cheeks. Findings showed that both of the treatments were able to effectively cure people with osteoarthritis and lift their sagging cheeks. Besides, the combination of two treatments effectively shortened the treatments of osteoarthritis and facial rejuvenation. It is necessary to provide training to professionals who combine the two treatments. In addition, more research should be conducted on the order and the recommended frequency of the treatments. Future research can be conducted on the techniques, medicine, and physiotherapy in the treatment of OA through the combination therapy of Traditional Chinese Medicine and Western medicine.


Chih-I Tsai and Jackson Chang

Asthma is a common chronic disease. Many patients who had asthma for many years and it was believed that asthma was difficult to be cured. Through clinical observation, the researchers found that many asthma patients had similar physical signs. They had bulge on their side of neck (sternocleidomastoid muscle). The researchers used acupuncture and cupping therapy in this study to cure asthma patients. Findings showed that acupuncture and cupping therapy were effective ways to cure asthma patients. Besides, acupuncture and cupping therapy shortened the number and time that asthma patients spent on medical treatments and further saved medical resources.


Chih-I Tsai

In Chinese, we called joints as "guanjie". A joint area includes one area called "guan" and another two areas called "jie" which are separately connected to each end of "guan" area. Joints contain ligaments and tendons. Ligament locate in "guan" area while tendons appears in "jie" area. Through Four Fingers Theorem, the researcher found that each "guan" area or each "jie" area was the width of four fingers. Findings showed that human eyes belong to joints. In addition, it is believed that preserving joint health was beneficial to maintain eye health.


Tsai Tsung-Ying, Chieh-Yun, Cheng, Liang-Yu, Shyu and Yi-Ping Chao

In our previous studies, it has been pointed out that a two-dimensional electrocardiogram (ECG) feature image of 150*150 pixels can have better performance in premature ventricular contractions (PVC) classification using convolution neural network (CNN). In this study, we investigate further on how to optimize the structure of CNN. The two-dimensional ECG feature maps are fed to different CNN classifier with different number of layers. Additionally, the influence of different activation functions on classification performance are also evaluated in this study. The results indicate the CNN with 12 convolution layers and rectified linear unit (ReLu) achieve best results.


ZHI-HAN ZHANG, TAI-HUA YANG and MING-SHAUNG JU

Recently, the arthroscopic instruments and surgical techniques have been advanced by leaps and bounds. Although arthroscopic surgery has many advantages compared to traditional surgery, however, during the operation, an assistant is often required to assist the surgeon to hold the arthroscope so that the surgeon can conveniently use his/her hands to perform precise procedures. Hand tremor of the assistant and the cooperation of the passive movement will affect the accuracy of the arthroscopic field image, resulted in sway, blurring, and out of focus of the operative field thus affecting the judgment and efficiency of the surgery. In this study, an arthroscopic robotic-arm auxiliary system that can serve as the ‘third hand’ and replace the assistant was designed. Using the system the mounted arthroscope can be adjusted to any position and orientation through a seven-degree-of-freedom mechanism and stably and easily locked through an electromagnetic brake system. In particular, a gravity compensation system was designed to balance the gravitational moments, allowing surgeons to operate smoothly without changing usage habits, and prevent the robotic arm from falling during the operation. Integration of the electromagnetic brake system and the gravity compensation system may improve the quality of arthroscopic images and reduce the risk in arthroscopic surgery.


Ching-yi CHANG

The importance of medical equipment have a correct and efficient performance for hospital patient. Hospitals and other medical centers can have hundreds or even thousands of pieces of medical equipment. A complete management system is essential for management to understand the present conditions of equipment. Currently, our existing medical equipment management operating system (MOS) is not rapid and automatic. Therefore, the purpose of this system was to enable equipment end-user or facility engineers to rapidly obtain detailed equipment information and to shorten the process of maintaining the equipment. The study by Lean Thinking was to design and develop the App of mobile device that could build a repair form, find a substitute unit, or browse the unit’s past performance data via QR code after equipment malfunction. The overall performance of the service can also be enhanced by upgrading the efficiency of the existing management system and improving the clinical engineer training. The results of the study included an increase in customer satisfaction by 17% and a reduction in the cycle time for repair by 20%. The App is already being widely used, with the utilization rate reaching 71%. The new procedure developed in this study is a novel and efficient system for health professionals and engineers.


Ching-I Wu, Chien-Ho Lin, Meng-Ting Wu and Ming-Chang Chiang

Practicing motor skill with one limb is transferable to another limb. However, it is not clear whether training with different movement parameters, such as moving in one direction, would benefit learning for moving in another direction. The purpose of this study was to investigate whether implicitly acquiring a motor trajectory in one moving direction would benefit the learning of the same trajectory with another moving direction. A gamepad joystick was applied to track a monitor-displayed target trajectory and the learners’ performance. A within-participant design was applied where the learners practiced vertical movements followed by horizontal ones 2 days later. Performance accuracy was determined by the root mean square error (RMSE) between the target and learners’ trajectories. We found that RMSE for moving in the second direction was lower than that for the first direction. The pilot study suggested that implicitly learning of a movement trajectory in one moving direction was positively transferable to another direction.


Cheng-Tai Ho, Chien-Ho Lin, Meng-Ting Wu and Ming-Chang Chiang

Previous studies have shown that motor practice in a non-repetitive, or interleaved condition, while compromising performance during the practice/training phase, leads to more effective learning comparing to repetitive or constant practice. This indicates that making the practice context more difficult might promote motor learning, a phenomenon known as the contextual interference (CI) effect. One way to manipulate the difficulty of practice condition is to arrange the order in which multiple motor tasks are presented to the learners. In the current study, the participants practiced to move a cursor to match a target displayed on the computer screen by controlling a joystick with the dominant hand. In this way, they implicitly learned to trace a complex but constant trajectory. The participants practiced the same trajectory in both vertical and horizontal directions. One group of participants practiced the horizontal and vertical trajectories arranged in a pseudorandom order, while the other group finished practicing trajectories of one direction repeatedly before switching to trajectories of the other direction. The goal of this study was to examine whether higher CI practice, i.e., the pseudorandom order, would lead to a better learning outcome when participants practiced a trajectory-tracing task.


Cheou Sheng Sam Lim, Pang-Kuei Lee, Yu-Lung Chang and Ming-Chen Wang

Industry 4.0 also known as the fourth industrial revolution is a strategic planning enacted by the German government. The Industry 4.0 is focusing on the integration of industrial-related technologies, sales and product experience in order to create a smart factory with adaptability and resource efficiency. In addition, the contribution of Industry 4.0 is to achieve a high precision production or scheduling of existing resources for reducing unnecessary cost and waste. In this paper, the implementation of this technology to the large inventory system of a large hospital or pharmacy is introduced. This can not only reduce the manpower requirements, in thereby, reduce the cost, the approximate zero error rate in the system is crucially important. We can apply the concept of Industrial 4.0 to corporate the hospital’s information system, coupled with mature automatic warehousing technology, the approximate null risk and error rate are possible to achieve in terms of drug inventory management. During the importation of drugs, their types will be identified and classified by the computer vision. After sorting the order of drugs for distribution, the computer will decide whether the drugs need to be refrigerated or frozen. Next, the robot will transport them to the corresponding drug warehouse. When exporting the drugs, the pharmacist can call the robot for delivery by connecting the hospital’s information system or scanning work order. This not only reduces the manpower, a minimal amount of error rate in delivering the drugs can also achieve.


Chan-Yang Kuo, Ho-Chiao Chuang and Yu-Peng Wu

This study developed a two-dimension Dose Distribution Sim-ulated Program (DDSP) and simulated the two-dimensional dose distribution with a supersonic system. The dose meas-urement tool (Gafchromic EBT3 film) was used to verify the DDSP simulation. Similarity and feasibility of replacing EBT3 film. The two-dimension Respiratory Motion Simulated System (RMSS) reproduces the respiratory motion while using the ultrasonic system with the ultrasound image tracking algo-rithm (UITA) to capture the respiratory motion signal and input it to the DDSP to generate the simulation. Simulated Dose Distribution Map (SDDM). DDSP is a human-machine interface program developed under MATLAB's Graphical User Interfaces (GUI). The radiation dose is transmitted to the EBT3 film to generate a blackening trajectory, which is then converted into an actual dose distribution map (MDD) by a radiation dose conversion curve. The ADFR range of the nine respiratory patterns ranged from 0.93 to 1.21, with the ADFR results of real human res-piratory signals being better than the Sin waves. Among the 20%, 50%, 70%, and 80% IARs, the 50% IAR results were the best, ranging from 0.84 to 1.16. The CSF index is 0.87~1.23, 0.84~1.29, and 0.81~4.40 for 50%, 70%, and 80%, respectively. Gamma Index 3%/3mm passing rate of Sin 0.167 is as high as 98.62%, and the other three Sin waves are above 90%. Changed to the stricter 2%/2mm gamma passing rate, there is no significant decline, the Sin wave range is 89.03~95.13%.


WEIFU CHEN

Abstract— In recent years, cardiovascular disease has become the leading cause of death and disability according to the statistics by the World Health Organization. The most common form of cardiovascular disease being arrhythmia. Sometimes, it becomes time-consuming and difficult for clinicians to observe electrocardiogram (ECG) and analyze the arrhythmia. Fortunately, deep learning has brought great success in the fields of image recognition and biomedical signal analysis. The Convolutional Neural Network (CNN) is a such famous method of deep learning with advanced automatic feature extraction and robustness. In this work, we developed a novel system of CNN for automatic detection of arrhythmia based on ECG signals. The ECG signals were obtained from MIT-BIH arrhythmia database. We have obtained Normal sinus rhythm (NSR), Atrial Fibrillation(AFIB), Premature ventricular contraction (PVC), Premature atrial contraction (PAC), Left bundle branch block(LBBB), Right bundle branch block(RBBB) and Supraventricular premature (SvP) ECG signals. Our system has achieved an average accuracy of 67.14% for the aforementioned six types of arrhythmia. Our work has demonstrated its feasibility in clinical applications which can be served as an assistive tool for clinical doctors.


Zheng-Ying Fan, Chia-Yen Lee, Ching-Cheng Chuang and Hsueh-Chien Yeh

Schizophrenia is a common global disease that occurs in ap-proximately 1% of the world’s population. It has variety of different symptoms, such as linguistic, logical, and brain dys-functions. There are several ways to research schizophrenia using brain neuroscience, such as nuclear magnetic resonance, positron emission tomography, and functional near-infrared spectroscopy (fNIRS). fNIRS is widely used because it provides low-cost, non-invasive, real-time measurement. The physician assesses the severity of the patient’s condition on a scale of 1–7. Although the CGI scale is a rapid and easy way to diagnose schizo-phrenia, there is a subjective problem. In this study, we aimed to investigate and use of the fNIRS pilot in the development of schizophrenia and provide a more objective assessment for physicians. We simultaneously aimed to develop an fNIRS system that is cost-effective and can be used globally. In this study, the verbal fluency test (VFT) was conducted on both patients with schizophrenia and normal subjects. fNIRS was used to measure changes in oxyhemoglobin con-centration in the prefrontal cortex. The mean oxyhemoglobin concentration was analyzed using k-means to obtain an accu-racy of 73.7% between the two groups, which indicates signif-icant differences in VFT between the groups. The physicians provided the CGI four factor scores of each patient. Multiple linear regression analysis was performed using both the CGI four factor scores of each patient and the mean oxyhemoglo-bin concentration. We found that channels 13, 15, 16 to satis-fy the significant correlation. Using the channels 13, 15 ,16, we performed multiple linear regression analysis again on the CGI scores. This further analysis showed that channel 15 had the most significant negative correlation with the CGI scores. It was also shown that channel 15 is viable to establish a module for CGI and oxygenated blood concentration changes.


Jo-Ping Lee, Kai-Wen Huang, Wen-Yang Chou, Chi-Ying Lu and Hui-Hsin Lu

The aim of this study was to investigate the radiofrequency ablation (RFA) needle active tip with segmental electrical conductive area would produce an ablation zone with specific shape. In ex-vivo bovine liver, RFA ablation zone were created by using monopolar probe with or without specific insulation pattern at 60 W to 6 kcal. RFA probe with specific insulation pattern was made by adhering insulation tubes to the conductive area of the RFA monopolar probe to produce a conductive surface area with specific pattern. The length of the isolated and conductive segments depended on geometry calculation. Ablation diameter, length, and spherical ratio (diameter/ length) were measured at gross pathologic examination and statistical-ly analyzed by using the paired Student t test. A p value less than .05 was considered to indicate a significant difference. Spherical ratios equal to 1 indicated a spherical ablation zone. The ablation length of the probe with insulation pattern was significantly shorter than the conventional monopolar probe (3.53±0.15 vs. 3.80±0.26 cm, p< 0.05) but not the ablation diameter (3.10±0.10 vs. 3.04±0.05 cm). Also the probe with insulation pattern created ablation zones with a higher spherical ratio (0.88 vs 0.80, p< 0.05) than did the conventional probe in ex vivo liver tissue. The insulation-pattern RFA probe created a more spherical ablation zone than did the conventional monopolar probe in ex-vivo liver tissue. Future application of this relationship of insulated segment pattern and ablation zone could be introduced to clinical RFA surgery. Following these results, the limitation of this new design was only feasible for 3-cm RFA probe.


Hamza Helal, Chao Yu Chen, Po Chien Chien and Yun Chien Cheng

This study investigates the effects of atmospheric-pressure cold plasma (APCP) generated short-life reactive oxygen and nitrogen species (RONS) by comparing the effects of long-life RONS and short-life RONS with long-life RONS on A549 cells. Prior studies have shown that the inhibition effect on cancer cells of plasma was higher than that of long-life species, such as H2O2 and NO2-. Researchers assumed that short-life species such as OH radical generated by plasma plays and important factor. In this work, PBS was used as treatment medium and its thickness was adjusted to control the concentration of OH radical reaches cells. Hence, we can compare the effects of long-life species and short-life species with long-life species on A549 cells. We used the terephthalic acid (TA) to detect OH radical. As a result, the highest concentration of OH radical in PBS appeared at 0.31 mm depth and far to 0.63 mm depth. In future, we will investigate the short-life RONS effects on cancer cells.


Cheng-Ye Chen, Zhe-Chen Liu, Yu-Hsiang Fang, Ting-Hsin Hung, Chia-Chun Chang, Yu-Ming Hung, Yao-Chin Wang, Yung-Hung Hsieh and Ben-Yi Liau

This study is to design and develop the intelligent automatic pill box system using 3D printing technology. The structures of the pill box and roating gear were created by using 3D printing machine. We adopt Arduino which controls the rotation and halt of the motor to dispense the pills to arrive at the quantity in need. This will be the first steps towards a fully automated process. Mobile phone can connect the intelligent automatic pill box system by the way of Bluetooth and to set parameters of intelligent automatic pill box system. This system can be home-based apparatus design and it allows users to set medication time and pill type by the APP function from mobile phone. Moreover, it can remind the user when and remember to take the medicine. In the future, it can be a helpful device in home-care or clinical practical.


Jung-Teng Pan, Hsiao-Hsuan Huang, Chia-Yu Hsu, Liang-Yu Shyu and Chih-Kuan Chiu

Pain at the fascia tissue causes abnormal gait in most of the patients with plantar fasciitis. In clinical, abnormal gait must be evaluated by doctor then rehabilitated by physical therapist. In addition, considerable equipment are required for gait measurement. However, these commercial available gait facility can only be set up in the gait laboratory in large-scale hospital. Moreover, these equipment are cumbersome and expensive such that they are not portable by the patience. This study constructed a foot pressure insole system using five pressure sensors to measure patient’s gait conveniently. This simple plantar pressure analysis system is lower cost and light weight. By using an Android smart phone as the real-time signal analysis and storage platform, the system is not hinder by storage space and process time constraints. It can be used while subject is moving in order to measure the pressure distribution of the feet. Study was proposed and approved to compare before and after pressure distribution from patients with plantar fascia and analyze the gait cycle. It is expected that this system can review the differences between subject with plantar fasciitis and normal subject in order to assist doctors or physiotherapist in their diagnosis.


Yen Ling Sung and Shien-Fong Lin

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is characterized by pain, swelling, and stiffness of joints. Inflammatory reflex, one well-characterized molecular inhibit-ing mechanism, is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthri-tis severity in rats.


Tz-Chi Lin

Previous research on mechanical pain usually applies manual devices to induce pain, where stimulation parameters, such as the contact time, stimulation frequency, and position of stimulation are difficult to accurately control for repeated stimulation. The current research developed an automated mechanical stimulation system that delivered mechanical stimuli at an adjustable stimulation force output from a computer-controlled motor combined with a linear actuator. We found that mechanical pain induced by the stimulator, assessed using visual analogue scale (VAS), increased with the force output from the system. Moreover, under the same mechanical force, a longer skin contact time of the stimulation probe resulted in a stronger mechanical pain. Our findings supported that the automated mechanical stimulator is an effective tool to investigate mechanical pain.


YI-JHANG WU, Wei-Ting Wang and Ioannis Manousakas

Improper ultrasound propagation produces reflection waves. When the impedance at the signal source is not the same with the impedance at the Load side it will produce reflection waves. The smaller the reflection wave, the more ultrasound power tissues or cells receive during ultrasound treatment. This study is using the MAX2016 IC to design a forward and reverse power meter connected to a bi-directional coupler. An Arduino board reads the values and displays them on an LCD. Using this system, the value of incident wave and reflection wave can be obtained. Knowing the exact values of the reflection wave allows for adjustment so that reflection can be minimized. Finally, a commercial ultrasound power meter was compared with the MAX2016 based power meter to confirm that they have similar characteristic.


Yi-An Liou, Kuen-Cheng Ju and Chih-Yu Wang

Traditional Chinese medicine can stimulate specific acupuncture points of the human body through acupuncture, massage, pressing, and moxibustion. It can activate the meridian and cure the disease. The purpose of this study is to establish a acupuncture points real-time image system and to realize the technique of augmented reality through depth camera. The plan is to use depth cameras and Python Opencv, to achieve the following objectives: (1) Use the acupuncture points detector to find out the acupuncture points position and mark it. (2) Combine the image with the real-time image to realize augmented reality technology and automatically mark the location of important points.


Hong-Lin Ke, Wen-Yen Lin and Ming-Yih Lee

Wearable cardiac health monitoring and myo-cardiac function assessment are emerging topics for realization of any intelli-gent mobile heath devices in evaluating performance of the cardiovascular system. In this study, a multi-channelmechanocardiogram (MCG) assisted with cardiac performance monitoring gateway were developed to interpret myo-cardiac functions of the cardiovascular system, such as left ventricular ejection fraction (LVEF), and provide early warning to the risk subjects. The real-time wireless gateway system for the multi-channel MCGs and ECG data acquisition, pre-processing and transmission was designed and implemented. It is an embed-ded system with mixed-signal circuits to measure multi-channel MCG signals and one lead ECG signal as well as to act as the core of a wearable mobile cardiac health monitoring system. The firmware design and timing verification for signal pre-processing are also carefully examined. The quality of output signals is validated, analyzed, and found to be highly correlated with myo-cardiac functions and linked to certain heart diseases, such as heart failures (HF). All the features of this gateway make the system more portable and suitable for the realization the technologies into a wearable cardiac health monitoring system. This gateway system not only reduces the total cost of the hardware platform for multi-channel MCGs/ECG cardiac activity monitoring system from US$ 12,000 (used in initial study) to US$ 130 (presented in this study) but also provides the mobility and capability for real-time data analysis and disease detections. Not only the multi-channel MCG system is capable of eval-uating the myo-cardiac functions, the system can also provide as a feasible solution for continuous heart rate variability (HRV) monitoring and detection. In this study, the correlation between R-R interval from ECG, which is used for HRV evaluation traditionally, and AO-AO interval, which is a new index from multi-channel MCG system, is compared. The experimental results show that the correlation coefficient between R-R interval and AO-AO interval is up to 0.99 on the same cardiac cycle. It was confirmed that the MCG and the ECG measurement of the cardiac cycle have a high intensity positive correlation. Therefore, the cardiac cycle measured by the MCG can replace the ECG and will become a new tool for clinically estimating heart rate variability. This gateway is a milestone for translating the concept of a multi-channel MCG system into a wearable device for cardiac health monitoring and myo-cardiac function interpretation system which then can be applied for the home-based or clini-cal usages to detect certain cardiovascular diseases, such heart failures. This system has brought international attention and was reported by the publication “Impact: Research” as one of the projects around the world with most potential impacts. The system can also works as a wearable solution for continu-ous HRV monitoring.


Chih-Chieh Huang, Wen-Yen Lin and Ming-Yih Lee

In this work, an accelerometer-based respiratory detection algorithm was developed when the subjects are in both static postures and dynamic activities. The algorithm was also veri-fied with a wearable smart clothes on 30 testing cases from male and female subjects in static postures and 5 testing cases when subjects were in dynamic activities, such as walking and running. More than 97% of accuracy is achieved by compar-ing with the detection results from respiratory belt conducted simultaneously in static cases and more than 85% of accuracy is achieved in dynamic cases. This clothes and respiratory detection is extremely useful to monitor human’s respiration when the subjects are in sleep and hence could be used for the detection of sleep apnea syndrome. Moreover, it could also help to monitor the respiration frequency of the subjects in their activities of daily life (ADLs). In recent years, tracking respiratory signals has gradually attracted attention in the application of medical care. A spi-rometer is the most commonly used instrument in lung func-tion test to measure air-flow velocity and the volume of lung clinically. However, there is no easy and comfortable way to obtain respiratory signal continuously. In the diagnosis of obstructive sleep apnea syndrome (OSAS), measurement of nasal-oral air flow along with respiratory belt detection are used in polysomnography (PSG) for the continuous monitor-ing of breathing signals and which are not comfortable at all for long-term monitoring especially in the sleep. There are other technologies for respiratory detection, such as detection of slight chest movement through radar, vision-based detec-tion and estimated from ECG signal, but the usages of these technologies either are restricted on the sites with proper instruments installation required or are lack of volume infor-mation for some applications. Consequently, they are not easy to be implemented as a wearable device for easy and comfort-able usage. When people are breathing, the diaphragm moves up and down accordingly. Diaphragm performs an important func-tion in respiration: as the diaphragm contracts, the volume of the thoracic cavity increases and air is drawn into the lungs, that is the inhalation; as the diaphragm relaxes, it causes the tissue to put pressure on the lungs to expel the air, and that is the exhalation. As the results, the respiratory signal can be monitored. The works on accelerometer-based respiratory signal detection to detect the movement of the diaphragm were not that much. Some research works used accelerometer to measure respiratory frequency during speech or installed accelerometer on the seat-belt of the driver seat in the car to detect the respiratory signal and further process with Empiri-cal Mode Decomposition (EMD) algorithm to monitor driver's respiration. In this study, wearable smart clothes instrumented with an accelerometer sensor is used to verify the developed respirato-ry detection algorithm. The smart clothes is easy to use and comfortable to wear and hence it is suitable for long-term monitoring. The validations was conducted with healthy sub-jects in the supine position to emulate the sleep posture. As a matter of fact, the system would be very useful for respiration monitoring during sleep and which could be applied for many sleeping related issues, such as sleep disorder problem, sleep quality monitoring, and especially for the OSAS. The respiratory detection in dynamic activities, such as walking and running, were also developed. The Ensemble Empirical Mode Decomposition (EEMD) algorithm were used to dissemble the measured signals into the intrinsic mode functions (IMF), which consists of different components of signals in different frequency. Comparing with the data de-tected from respiratory belt, the accurate signals containing the actual respiratory rate can be found in one of the IMF signals. However, the most challenged part is to decide which IMF signal to choose for accurate detection. Therefore, more testing were conducted in dynamic cases where we had the testing subjects walked or ran on the treadmill on different speed. After the tests, we can concluded that when the speed are greater than 4 km/hr, the IMF7 signal can deliver more accurate information of respiratory rate. As the speed is below 4km/hr, IMF7+8 could provide more accurate signal. In all cases (speeds), more than 85% of accuracy can be achieved when the right IMF components are selected for the respirato-ry signal detection.


Yu-Xian Zhu, Yi-Ning Zeng and Min-Hsien Wu

Cancer metastasis is a leading cause of cancer-derived death. Although the studies relevant to this issue have been carried out for more than a century the mechanism of cancer metasta-sis is still not fully clear. With the recent studies on circulating tumor cells (CTCs) they hold immense potential to provide more valuable information on the mechanism of cancer metas-tasis. In current CTC studies, however, CTCs are normally defined as the cancer cells in blood circulation that express specific surface antigens-EpCAM(CD45neg/ EpCAMpos). The studies based on this could miss the other metastatically more meaningful cancer cells due to high heterogeneity of CTCs (CD45neg/ EpCAMneg). To address these issues, we aim to develop an optically-induced dielectrophoretic force-based microfluidic biochip system for high purity (ideally 100%) cell isolation. We will use it to isolate target cells in a blood sample that includes leukocytes (CD45pos), conventionally defined CTCs (CD45neg/ EpCAMpos), and an unknown cell group (CD45neg/ EpCAMneg) in this study. In the future works, the technique of real-time PCR will be utilized to analyze the expression of cancer-related genes [e.g. genes relevant to stem cells, cancer stem cells (CSCs), or Epithelial- Mesenchymal Transition (EMT)] of the cell species abovementioned. Through these investigations, we will examine if there are “atypical CTCs” (e.g. the cancer cells that express CSCs or EMT-related genes) in the unknown cell group.


Zhan Wan-Ting, Zi-Xuan Huang, Liang-Yu Shyu and Li-Ang Lee

This study developed a system that can assess the snoring of patients with apnea, and the actual measurement of snoring patients' signals is compared with the current hospital gold standard PSG. The results of the experiment were verified by doctors and professionals. The detection accuracy of the sound was 93.97% and the sensitivity was 95.69%. This proves that the sensor can accurately detect the click and display the time of the event.


Jia-Jung Wang, Meng-Hsuan Chuang and Cheng-Yo Yen

The study utilized a non-invasive wireless measurement system by our laboratory to register the vibroarthrographic signals from the three positions (lateral condyle, mid-patella and medial condyle) of a knee joint. This study recruited 125 subjects who were divided into Control group (N=29) with normal knee joints and Osteoarthritis (OA) group (N=96) with degenerative knees. Each participant was asked to perform the active swing, passive swing, and step-up and –down motions. All 10-sec vibration signals from the three positions in the 125 subjects were analyzed using the approximate entropy (ApEn) method. It was found that the mean ApEn values (0.766±0.247; 0.727±0.204) of vibration signals recorded from the mid-patella and medial condyle were significantly greater in Control group than those (0.707 ±0.112,0.654±0.174) in OA group during the active swing (all P<0.05). In addition, similar tendency appeared in the other movements. Thus, these findings suggest that the ApEn value may become a useful index for differentiation of OA from healthy knee joints.


Jia-Jung Wang, Xuan-Hao Su, Hsin-Yen He, You-Heng Su and Wei-Kung Tseng

The laser Doppler flowmetry (LDF) was applied to record microvascular perfusion on the foot bottom in 22 healthy participants (Control group) and 13 patients with diabetes mellitus (DM group). Every subject was asked to experience an episode of 3-minute ankle occlusion. The LDF signal acquired during the 8-minute baseline, 3-minute occlusion and 6-minute post-occlusive reactive hyperemia (PORH) was analyzed, on a 1-minute basis, using the wavelet transform. We found that the mean PSDs corresponding to the endothelial NO-independent and NO-dependent metabolic activities varied with time in both Control and DM groups. In addition, both of the mean PSDs associated with the endothelial function were smaller in DM group that in Control group. Thus, microvascular endothelium modulates the skin microcirculation in a dynamic manner. Also, patients with DM have impaired endothelial function in skin microcirculation as compared with healthy subjects.


Shi Yi Wu, yashbir singh, Deepa, SU,HONG JIN and Wei-Chih Hu

Recent studies suggest that central blood pressure(cBP) is more strongly related to cardiovascular events, and many non-invasive devices are available to measure the cBP. Most of them are measured by the oscillometric method, yet the most critical one to study the blood pressure waveforms. But due to excessive circuits in these devices, which tend to cause distortion in the acquisition of signals. Also, the way of deflation affects blood pressure waveforms. Signal acquisition at the deflation time with constant pressure method emphasizes the clarity and authenticity of the signals. These signals can be used effectively and accurately without excessive load and distortion of signals. Therefore, we have developed a stable and compact system for extracting non-invasive blood pressure waveforms to estimate the cBP. A low-pass filter is used, with the sampling rate of the system up to 300Hz. The extracted pulse signal contained small noise interference and high signal-to-noise ratio(SNR), which is suitable for analysis and signal processing.


Wen-Hung Chao, Po-Hsuan Chung, Cheng-Min Lee, Yu-Wei Yao and Chia-Yi Lin

In recent years, electronic products have changed the way of human life. The innovation of electronic products not only changed the life way of human beings, but it also caused the environment to be full of sound stimuli to affect our psychology. Our brains are affected by these stimuli. In previous research, the noise affects our mental and causes an additional burden in the body. For this reason, a set of sound stimulation experiments were conducted in this study. Ten subjects were asked to pay attention to four kinds of experimental tasks for deviation stimuli and to discuss the sound with regard to the concentration a quantity and difficulty of the task whether affect the brain activity reaction. Each experiment gave a standard and deviation stimulus of 1000 Hz and 1500 Hz, respectively. Electroencephalograph (EEG) signals were acquired, refer to international 10-20 system to put on 21-lead scalp electrodes and then analyzed with MALAB. The results show that in the case of four different experimental sound stimulation tasks, the event-related spectrum power (ERSP) of sound count experiment (SC) showed the highest power variations in four different experimental sound stimulation tasks. The ERSP of the brain from SC experiment are higher than those of the brain from the sound button experiment (SB). The button task is the low difficulty of brain activity and the count tasks is the high difficulty of brain activity.


CHOU KUOFENG, HUANG YI LING, LI,RUEI-SHIUAN, ZHAO YAN QING and WU,XIN-YI

Obstructive sleep apnea is one of the main causes of sleep disorders. When patients feel poor sleep quality, they can use the wearable sleep test device to screen. If there is a record of sleep breathing stop, they need to go to the hospital overnight for the polysomnography. However, the current design of the wearable sleep breathing apparatus must be inserted into the nasal cavity, which is uncomfortable for the wearer, and the results must be processed by the computer before being presented. This study attempts to construct a simple sleep breathing monitoring device that combines a mobile phone application to provide the comfort of the wearable device and the instant display of monitoring results. The new system consist of a temperature and humidity sensing chipwhich is usedto measure the difference between exhalation and environmental temperature during nasal breathing, a microprocessor chiplinkit 7697, a Bluetooth module, a special mask and a mobile application. The special mask has a separate inlet and outlet for inhalation and exhalation, so that the temperature sensor can record the dynamic temperature change of the breathing process. The temperature and humidity sensorDHT22is fixed to the exhalation area of the special mask. The temperature sensing signal is filtered and amplified by the microprocessor chip and the threshold value is calculated. The threshold is divided into the temperature difference threshold and the interval counting threshold. When the temperature difference threshold is used as the effective breathing action index, the interval counting threshold is used as the obstructive sleep apnea indicator. In this study, the threshold values and indicators were determined experimentally using the temperature difference test of the expiratory cycle and the ambient temperature, the different breathing interval test, the correspondence between the program counting period and the breathing interval. The times of breath stopping and low-efficiency breaths during measurement period that record by the micro-processing chipare transmitted to the mobile phone through the Bluetooth module. The mobile phone program operation panel includes a room temperature value correction button, a measurement start button, and a breathing disorder index transmission button.


Chi Yen Shen, JING JIE CHIU, Min Wen Yang, Mei Hui Chung and Tien Tsan Hung

The design of modern chemical sensors focuses on highly responsive devices that can efficiently transform chemical responses into measurable electronic signals. These devices should be able to use for wireless communication and are small size for developing portable and miniaturized detection chips. Surface acoustic wave (SAW) devices are some of the most prominent sensors for chem-ical sensing applications. In this study, a single-phase unidirectional transducer (SPUDT) SAW device on ST-X quartz with low insertion loss (less than 10 dB) and single mode capability is proposed to be applied for detection of ppb-level NO. The equivalent circuit model incorporated with coupling-of-modes (COM) parameters was used to model and analyze characteristics of SAW devices and was demonstrated by experimental results. The simulated and measured results were consistency. In this study, The EWC/SPUDT configuration enhanced single mode selection and effectively guides the SAW energy transmission between input and output IDTs, and suppressed the level of the 3rd harmonic. A SAW sensor based on ST-X quartz substrate with EWC/SPUDT structure and single mode selection was fabricated. Then, the oscillator works at a single frequency that has higher output power of the fundamental signal, better suppression of harmonic level, and long-term frequency stability. The SAW sen-sors with EWC/SPUDT structure had a frequency shift of 502 Hz at an NO concentration of 50 ppb in dry air, response time of 56 sec and recovery time of 112 sec. The gas sensor experimental results also showed a SAW sensor with EWC/SPUDT structure toward ppb-level NO in dry air at room temperature has the superior sensitivity, fast response and recovery time. In the future, the development and improvement of SAW sensor for detecting ppb-level gases will be continued and to achieve the purpose of medi-cal detection.


Ting-Husan Wu, Shu-Jen Chiang and Chen-Yuan Dong

Cyclic immunofluorescence (CycIF) is a versatile procedure in which many colours staining alternates with chemical inactiva-tion of fluorophores to progressively build a multichannel image. Because of molecular diffusion, staining becomes a slow process that significantly procrastinates the completion of chemical processing. To solve this problem, recently, a novel electrokinetic method has been used to study rapid nonde-structive processing of porous samples. We utilize the alterna-tive electric field method in the agarose gel to accelerate the process. A 100 μm tumor tissue and a charged dye are loaded into a pre-cast well in the agarose gel, applied with alternative electric field. It is anticipated that the movement of charged ions penetrate into the depth of tissue without destroying the surface and allow efficient dye penetration.


Chu Ying Shiuan, Jhang De-Fu, Ye Jing-Jhao, Chuang Chiung-Cheng and Ye Cheng-Pei

In 2001, the Joint Commission Accreditation of Health Care Organization included pain assessment and treatment in the hospital assessment criteria, emphasizing that pain should be considered as a fifth vital sign and must be monitored and documented whenever and wherever possible. At present, questionnaires of the patient self-report type are used as the basis for pain assessment. This type of assessment does not immediately reflect painful feelings that change over time. That is, an effective and continuous monitoring technology for assessing pain becomes a key issue. In this study, the thermal stimulation experimental environment was used to simulate the feeling of pain in healthy people while a multi-physiological parameter real-time monitoring system was used to continuously monitor changes in photoplethysmography (PPG) characteristics and pulse wave variability (PRV) when pain occurred. The number of participants in the experiment was 5 (3 men and 2 women). While pain was stimulated in participants, the heart rate (HR) had a rising trend, while the heartbeat interval, low frequency (LF) and high frequency (HF) have a decreasing trend. When pain was gradually relieved, the HR dropped obviously, and the heartbeat interval, LF and HF have obvious changes in the upward trend. The above-mentioned multi-physiological parameter real-time monitoring system can effectively observe pain and changes in the percep-tion of pain. In the future, this can provide medical personnel with objective and immediate pain assessment to improve the overall quality of medical care


Chun-Hao Huang and Kin Fong Lei

Cancer metastasis is an important indicator of cancer progres-sion. Currently, the most common assay of cell invasion is performed with Transwell system. In this study, a microchan-nel impedance chip has been developed, that is different from Transwell assay. This device can observe cancer metastasis by a fluorescent microscope and analyze the metastasis time and speed by impedance analyzer. The impedance analyzer can accurately measure cell location. The experimental results showed that the microchannel impedance chip increases the accuracy of cancer metastasis analysis.


Jui-Teng Lin, Kuo-Ti Chen and Hsia-Wei Liu

The kinetics and the efficacy of anti-cancer via PDT and PTT are discussed. New and contrast features of type-I and type-II PDT are compared. Enhancement of the overall efficacy may be achieved via resupply of PS or oxygen during the light exposure. The synergic efficacy of PDT/PTT is sequence-dependent, with a preferred procedure of PDT followed by PTT. Optimal combination of light energy (dose), intensity and irradiation time may be achieved via Lin’s nonlinear law, Arndt-Schulz- Law (for therapeutic window) and Bunsen-Roscoe law (for reciprocity rule). Smart nanogels offer swelling capacity, stimuli sensitivity, large surface area, bioconjugation and encapsulation of bioactive substances.


Li-Wen Kuo and Shang-Hsiu Hu

Theranostic nanohybrids can potentially unite the unique feathers and reduce side effects for precision cancer therapy. However, the poor accumulation and limited tumor penetra-tion at tumor obstruct the manifestation of nanomedicine. Here, a hierarchical-targeted hybrid that doubles as stealth and magneto-lytic carrier that transports dual tumor-penetrative agents incorporating pH-responsive dendrimers and anti-cancer drugs was developed. Through convection-enhanced delivery (CED), the exosome-camouflaged hierar-chical-targeted nanohybrids amplify the tumor accumulation of drugs through the by-pass BBB and hierarchical targeting. Penetrative delivery of dual pH-Den and exosome to the deep tumor is actuated by magneto-thermal effects, which is able to generate the intense heat and disassemble the hybrids into few nanometers of components. The synergy of magneto-thermally drug-penetration and chemotherapy was delivered by the theranostic pH-Den/anti-cancer drug to orthotopic xenograft tumor, which significantly prolonged the survival time. This dual hierarchical and exosome- camouflaged delivery inte-grated with controlled-penetrated release from versatile parti-cles exhibits potential for clinic applications.


Jen-Hao Hsieh

Nowadays delivery of drug within responsive carriers that with high stability during long circulation in the body and effec-tively target and accumulate in cancer cells is demanded in per-sonalized medicine. However, the physiological barrier of the tumor restrict drug penetration delivery, and impedes drug car-riers to release their therapeutic agents into cancerous cells at the center of tumors. Therefore, engineering particles that can transport therapeutic agents deep into tumors is a key factor for tumor therapy. In addition, The clearance of nanoparticles (NPs) by mon-onuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Thus, engineering the shape, surface area, and size of Ag@Au alloy nanostructures is important in controlling NP−MPS interactions and improving the tumor uptake effi-ciency. Porous Ag@Au alloy nanoplates by controlled galvanic re-placement with Ag nanoplates as the sacrificial template, a sul-fite-coordinated Au(I) salt as the Au source, and polyvinylpyr-rolidone (PVP) as the capping agent. Due to the high stability of porous Au@Ag alloy nanoplates, special biomolecules can be combined to form a nanocarrier platform. Recently, the role of exosomes has also been highlighted in the scientific area with the potential of therapeutic molecules as they can mediate com-munication between cells and also immune related mechanisms. Here, a exosome-coated porous Au@Ag alloy nanoplates, is developed for tumor-targeted chemotherapy delivery with a controlled release profile in response to high-frequency mag-netic field (HFMF). It can improve biocompatibility and en-hance cellular uptake, including Upon fulfilling its mission of tumor homing and RES evasion.


Pei-Yu Tu, Yao-Wei Yeh, Po-Hen Chen, Tzu-Hsuan Chuang and Ping-Ching Wu

In recent years, nanotechnology has undergone revolutionary changes in medicine, especially in the case of cancer. Nanotechnology has formed a complete treatment plan from early prevention, initial development detection, precise positioning, and accurate drug administration. It is believed to improve the shortcomings of traditional diagnosis and treatment and may even reduce medical costs. Because nanoparticles have exceptional properties and ability to interact with cells, these magnetic nanoparticles can monitor changes in cancer cells and medications in real time. The drug delivery system of nanoparticles overcomes the limitations of traditional chemotherapeutic drugs in the human body. Through the encapsulation of polymer materials, the drug is prevented from being damaged during normal delivery to the tumor site, and at the same time, the drug is prolonged and accumulates in tumors. This phenomenon is known as enhanced permeability and retention effects (EPR effects). The overall goal of this study is to develop a multifunctional iron-platinum polymer nanoparticle with diagnosis and treatment capabilities to encapsulate the first-line chemotherapy drug paclitaxel with PLGA as a polymer material, and to develop iron-platinum nanoparticles with dual development effects. According to our results, FePt nanoparticles can enhance the inhibitory effect of the chemotherapy drugs, PLGA@Paclitaxel, on cancer cells. 1 mg/mL FePt-PLGA@Paclitaxel (6.25µg/mL PLGA@Paclitaxel) and the highest concentration of PLGA@Paclitaxel alone (25µg/mL) exhibited the same colony formation, which showed that FePt nanoparticles could weaken the proliferation of 4T1 cells and enhanced the inhibitory effect of the chemotherapy drug. At 0.5 mg/mL FePt-PLGA@Paclitaxel, the growth inhibition rate of cancer cell is as high as 50%. Therefore, in the subsequent tests, we used 0.5 mg/mL FePt-PLGA@Paclitaxel (6.25µg/mL PLGA@Paclitaxel) as the experimental group.


TUNG MEI-TZU

We synthesized a dual anticancer theranostic fluorophore, EO, which emerged the dark cytotoxicity and photodynamic therapy characters to cancer cells. Following the bioassays evaluations, chemotherapy EO can specifically localize in mitochondria to cause mitochondrial dysfunction and then induce apoptosis in cancer cells but not normal cells. Simultaneously, phototherapy EO is able to generate particular reactive oxygen species (ROS) to undergo type I photodynamic therapy (PDT) programme under irradia-tion. It is interesting that slight irradiation may alternatively accelerate intracellular EO delivered to nuclear, instead of performing phototherapy, to triggered chemotherapy and synchronously cause fluorescence color switch. That is, the photo-induced nuclear transport of this chemo-phototherapy molecule can be a dual anticancer theranostic drug candidate, especially for cell death mark-er, with the intracellular fluorescence colors switching between cytoplasm and nucleus.


Xiang-Hao Zeng, Yi-Ting Shu, Kuei-Chi Lee, Bo-Yuan Shen, Min-Hua Chen and Ming-Fa Hsieh

Cholangiocarcinoma is the second most common hepatobiliary tumor, which is generally a locally invasive tumor that occludes the biliary tree and leads to cholangitis and liver failure. Until now, tumor resection has been the only potential cure for cholangiocarcinoma. Unfortunately, even with resection, the survival rate with five years can decrease to 11% at most and more than 50% of patients still remained at unresectable stage. Inoperable patients with advanced cholangiocarcinoma typically have obstructive cholestasis. So far, the primary standard method of treatment has been biliary stenting. However, this treatment can prolong survival time slightly by providing temporary biliary drainage. Therefore, in this study, we are going to develop a localized eluting stent, covered with nanodrug to prolong the survival time by reducing tumor burden. The design of prototype used polyurethane as the material of the backing layer, and gelatin blends were used in drug-storing layer with nanodrug loaded. The optical microscopy revealed that the backing layer was formed in fine fibers from electrospinning, while drug-storing layers, attributed to the droplets from electrospraying process. The covered membrane, the morphology of which was observed by scanning electron microscopy, covered the stent surface homogeneously without crack appearances. The release study further indicate the controlled release of drug eluted from stent via different ratio of gelatin blending. The results provide a proof of concept of nanodrug-eluting stent and a new prospective of localized controlled release treatment for cholangiocarcinoma disease.


YING-AN TSAI, Yun-Yu Chen, Cheng-An Lin and Ching-Yi Cheng

Free radicals as know as ROS,that the most fundamental factor in causing or disease in humans. Moderate free radicals can regulate blood circulation in the body, that helping blood vessels to contract. However, excessive free radicals can have serious effect. Epithelial tissue is the outermost layer of the human , which isolates pathogens and regulates body tempera-ture to prevent water balance. It will have different thicknesses depending on the location. For example, the skins thickness around the 0.5 mm. Therefore, it is also the first area to aging of body, and ultraviolet rays induce the proliferation of ROS in the cells. Lipid proteins, damage to DNA, indirect atopic der-matitis or an increase in cancer-promoting factors lead to an increased risk of melanoma. In this study, a one-pot synthesis method was also used to synthesize a fluorescent gold nanoclusters and surface modifi-cation of R-α-Lipoic Acid, referred as AuNCs-DHLA. Using UVA of 240 mJ/cm2 ( UVA=365 nm) induced ROS in HaCaT cell. The results of MTT assay showed that treating 200 nM AuNCs-DHLA had the best biostability and could be effective-ly with HaCaT cells for 3 hours. Capture free radicals induced by UVA.


SUNG YUAN CHING, Meng Hsun Lu, Wen Chun Wei, Chung Wei Chen, Kai Wen Huang and Jen Jie Chieh

The vibration sample magnetometer (VSM) has always been the basic instrument for the detection of magnetic property. These cheapest one costed several millions even though their patents are expired. It resulted in only a few academic circles and no population in industries. This work proposed not only a breakthrough of detection principle for economic and com-pact system, but also a novel magnetic immunoassay technol-ogy. In comparison to current VSM, three uniqueness are shown: 1. [Time-varying magnetic field by magnets] Instead of a high cost, heavy, large-power-consumption, and additional water-cooling equipment electromagnet, the innovation of a time-varying net magnetic field was to produce the effective magnetic vector in axis of the pickup coils by rotating different rings of combinational magnets with different strength of magnetic fields. 2. [Vibration mechanisms] Instead of the current non-metallic vibration sample rod coupling with an expensive motor, its controller, and a complex alignment, a simple acoustic waveguide as a sample holder integrating the cheap buzzer and a micro tube for any type of sample. Besides the general material characterizations in general industries, it will be also powerful for the clinical in-vitro diagnosis with magnetic nanoreagent, like the promising examination of alpha fetoprotein (AFP) antigens for the screen of liver cancers shown in the results.


Chi-An Chen, Cheng-Yi Huang and Cheng-An Lin

In this study, gold (Au) was used as precursor to produce fluorescent gold quantum clusters. Replaces quantum dot materials that are currently shallowly hazardous to biological environments. In the process of gold quantum cluster synthe-sis we use high-resolution centrifugation, rotary vacuum decompression concentration, freeze-drying, thin layer chro-matography(TLC), column chromatography, to purify the completely reduced yellow fluorescent gold quantum clusters. Or by polymer grafting to improve quantum yield and light-emitting lifetime and stability, it is expected to enhance the development of related biomedical materials or related applications in the future.


Lin Xing-Ting and Chi-Hsien Liu

Curcumin is a phytochemical having antibacterial, anti-inflammatory and anti-oxidant bioactivity. Nanoemulsion is now applied in the fields of pharmaceuticals, functional foods, and cosmetics as one of the efficient carriers. In this study, we will explore the stable formulation of self-assembled nano-thickness coating in layer-by-layer nanoemulsions. The main principle in nanoemulsion used the sequential adsorption of positively and negatively charged polymers on the surface of oil droplets. Biopolymers such as cationic chitosan and anionic pectin were layer by layer adsorbed and the size and zeta potential of the nanoemulsions were measured. The stability of the nanoemulsion was evaluated by the phase separation analysis. When the chitosan concentration was 0.3 mg/mL, the cationic nanoemulsion had the smallest size and converted the zeta potential from negative (-22.8 mV) into positive charge (18.8 mV). Subsequently, different concentrations of anionic pectin were screened and the particle size decreased accordingly. The 2-layer nanoemulsion was stabilized in the pectin range of 0.6-1.4 mg/mL with zeta potential among (-15.2~-18.2 mV ). We used centrifuge (5000rpm, 1 min) to accelerate the oil phase separation. Among the prepared nanoemulsions, the formulation containing 0.3 mg/mL chitosan and 1.0 mg/mL pectin had the lowest turbidity and stable size distribution (234.6 ±2.17 nm). This stable layer-by-layer nanoemulsion will be applied to oral delivery in the near future.


TE-I LIU, Ying-Chieh Yang, Wen-Hsuan Chiang, Chun-Kai Hung, Yuan-Chung Tsai, Chi-Shiun Chiang, Chun-Liang Lo and Hsin-Cheng Chiu

Radiotherapy is one of the general approaches to deal with malignant solid tumors in clinical treatment. To improve ther-apeutic efficacy, chemotherapy is frequently adopted as the adjuvant treatment in combination with radiotherapy. In this work, a ROS-responsive nanoparticle (NP) drug delivery sys-tem was developed to synergistically enhance the antitumor efficacy of radiotherapy by local ROS-activated chemotherapy, taking advantages of the enhanced concentration of reactive oxygen species (ROS) in tumor during X-ray irradiation and/or reoxygenation after X-ray irradiation. The ROS-responsive polymers, poly(thiodiethylene adipate) (PSDEA) and PEG-PSDEA-PEG, were synthesized and employed as the major components assembling in aqueous phase into polymer micelles in which an anticancer camptothecin analogue, SN38, was encapsulated. The drug-loaded NPs underwent structural change including swelling and partial dissociation in response to the ROS activation by virtue of the oxidation of the nonpo-lar sulfide residues in micelles into the polar sulfoxide units, thus leading to significant drug unloading. The in vitro per-formance of the chemotherapy from the X-ray irradiation pre-activated NPs against BNL 1MEA.7R.1 murine carcinoma cells showed comparable cytotoxicity to free drug and appreciably enhanced effect on killing cancer cells while the X-ray irradia-tion being incorporated into the treatment. The in vivo tumor growth was fully inhibited with the mice receiving the local dual modality treatment of X-ray irradiation together with SN38-loaded NPs administered by intratumoral injection. The comparable efficacy of the local combinational treatment of X-ray irradiation with SN38-loaded NPs to free SN38/irradiation dual treatment corroborated the effectiveness of ROS-mediated drug release from the irradiated NPs at tumor site. The IHC examination of tumor tissues confirmed the significant reduc-tion of VEGFA and CD31 expression with the tumor receiving the local dual treatment developed in this work, thus account-ing for the absence of tumor regrowth compared to other single modality treatment.


Liang-Hsin Chen and Tzu-Wei Wang

Injectable hydrogel has been widely used for different biomed-ical applications such as in tissue engineering or drug delivery system due to their in situ gelation property and the ad-vantage of minimal invasion. In this study, four-armed poly ethylene glycol (4-armed PEG) polymers are crosslinked by complementary nucleic acid sequences to form the network structure of the hydrogel with an enzyme-sensitive peptide motif in between. Nucleobase pairing is a specific hydrogen bonds forming process through self-assembling process be-tween two well-designed nucleic acid sequences. As crosslink-ers, nucleic acid sequences provide hydrogel injectability and self-healing properties. Moreover, the mechanical property of the hydrogel can be tuned easily by designing different nucleic acid base pairs. Since gene therapy has been considered as a powerful approach for the treatment of a variety of diseases, functional double stranded nucleic acid sequences, including siRNA and plasmid DNA, can serve as a binder and a thera-peutic molecule as well. Of note is that DNA is able to become a delivery agent for several DNA-intercalating drugs such as doxorubicin. The novelty of our design is that the enzyme- sensitive peptide between the 4-armed PEG and the nucleic acid sequences deliberately controls the release of both func-tional nucleic acid sequences and DNA-intercalating drugs. With systematic release of multiple therapeutic molecules and agents, the hydrogel can show great synergistic effect with multiple combinations. For example, by simply changing the therapeutic nucleic acid sequence and drugs, the hydrogel has great potential to fit the needs of the treatment for a wide range of diseases.


Po-Ting Wu, Yu-Wei Tai, Shu-Pao Wu, Ping-Shan Lai, Jiashing Yu and Mei-Yi Liao

Cu@Cu2O@PSMA polymer nanoparticles (Cu@Cu2O@polymer NPs) with near-infrared (NIR) absorp-tion were successfully synthesized in a single-step oxidation reaction of Cu@PSMA polymer NPs at 100 °C for 20 min. The shape, structure, and optical properties of the Cu@Cu2O@polymer NPs were tailorable by controlling the reaction parameters, e.g., using the initial Cu@PSMA poly-mer NP as a template and varying the halide ion content, heating temperature, and reaction time. The Cu@Cu2O@polymer NPs exhibited robust NIR absorption between 650 nm and 710 nm and possessed superior oxidation resistance in water and culture media. In vitro assays demon-strated the low cytotoxicity of the Cu@Cu2O@PSMA poly-mer NPs to HeLa cells through an improved cell viability, high IC50, low injury incidence from the supernatant of the partly dissociated Cu@Cu2O@PSMA polymer NPs, and mi-nor generation of reactive oxygen species (ROS). More im-portantly, we demonstrated the inorganic Cu-based nano-composite (+0.34V vs NHE) was degradable in an endogenous H2O2 (+1.78V vs NHE) environment. Cu ions were detected in the urine of the mice, which illustrates the possibility of ex-traction after the degradation of the Cu-based particles. After an examination of the HeLa cells received the Cu@Cu2O@polymer NPs and a 660 nm LED, the photoabla-tion of 50 % and 90 % cells was observed at NP doses of 20 ppm and 50 ppm, respectively. These results demonstrate that NIR-functional and moderate redox-active Cu@Cu2O@polymer NPs are potential next-generation pho-tothermal therapy (PTT) nanoagents because of combined features of degradation resistance in the physiological envi-ronment, enabling the delivery of efficient PTT; a possibly improved ability to selectively harm cancer cells by releasing Cu ions under high-H2O2 and/or low-pH conditions; and an ability to be extracted from the body after biodegradation.


Chin-Yuan Chang and Yu-Hsiang Lee

Prosthetic joint infection (PJI) is one of the most challenge issues in the clinic and the mortality rate attributed to PJI may be as high as 2.5% due to difficult-to-treat deep infection in the implant and/or imperfect one- or two-stage revision. To overcome the aforementioned challenges, in this study, the indocyanine green (ICG)-rifampicin (RIF)-encapsulated PLGA nanoparticles (IRPNPs) with combined photo- and chemo-therapeutics functionalities were developed. Through the characteristic analysis, the size and surface charge of the IRPNPs are 281.1 ± 5.16 nm and -29.4 ± 0.55 mV, respectively. The encapsulate rate of ICG and RIF are 78.98 ± 9.46% and 32.77 ± 3.01%, respectively, whereas the drug loading rate of ICG and RIF are 1.25  0.09 % 0.386  0.028%, respectively. In terms of the antimicrobial experiment, methicillin-resistant Staphylococcus aureus (MRSA) cultured in porous ceramic matrix were applied to mimic the scenario of PJI in vitro. After cultivation for 24 h in the presence of glucose, our data showed that the MRSA biofilm successfully grew up in the porous medium as demonstrated through crystal violet-staining approach. Based on colony analyses, our data showed that the IRPNPs were effective on biofilm destruction and MRSA eradication upon NIR exposure (808 nm; 6 W/cm2), and the resulting biofilm destruction rates led by IRPNPs with 0.875 and 1.75 uM of RIF were approximately 1.7- (P < 0.05) and 2.4- (P < 0.05) fold higher than that caused by equal amount of entrapped RIF alone. These outcomes indicate that the IRPNPs may serve a feasible/effective tool for antimicrobial treatment in a porous medium such as artificial joint.


Hsu Chiung Wen, J.R. Wu, C.Y. Kuo, Y.J. Liu, C.C. Lin* and L.C. Li*

In this study, a filter-like SERS filter was used for continue filtering the dialysate solution with lower concentrations. Bacteria accumulation on the surface of the SERS filter was achieved successfully after dialysate fluidic path through. Moreover, higher SERS enhanced can be achieved further after introduce with Au@Ag nanoparticles. Bacteria Raman and SERS fingerprints were collected and classified by pattern recognition technique. Our results showed a multiple enhancement SERS technique for clinical bacterial characterization with nice classification results. The filter-like substrate and nanoparticles are both easily prepared together with simple and low cost. The technique we reported here can be further apply not only clinical but also environment pollution and food safety analysis.


Ching-Yen Yeh, Chiranjeevi Korupalli, Wen-Yu Pan, Po-Ming Chen, Po-Kai Luo, Chun-Ju Chou, Yung-Seng Pang and Hsing-Wen Sung

Vaccination is the most effective tool for preventing infectious diseases. Although traditional prime/boost vaccine regimens are effective, multi-bolus regimens are often difficult in the developing countries due to limited healthcare access. A single-injection vaccine that can release or persist antigen over an extended period of time, and rapidly induce a robust and sustained protective antibody responses may overcome these obstacles. In this work, a novel hydrogel-NP composite system, which is prepared by entrapment of OVA loaded TMC/gamma-PGA NPs inside the catechol-modified hyaluronic acid (HA-CA) hydrogel (OVA@TMC/gamma-PGA/HA-CA), is developed for long-lasting delivery of antigens. From in vitro study, data shows that OVA@TMC/gamma-PGA/HA-CA composite can be uptake by antigen-presenting cells (APCs), and increase their surface expression of CD80 and CD40. In the animal study, we found that immune cells can be recruited to the nanocomposite, leading to a long-term antigen-specific antibody titer up to 12 weeks. Overall, in this study, we successfully develop a single injection vaccine via the OVA@TMC/gamma-PGA/HA-CA nanocomposite system which can elicit robust and prolonged antigen-specific humoral responses.


Wen-Tyng Li and Yi-Chen Lin

Current fluorescent reagents for cell imaging have the disadvantages such as photobleach and unsuitable for long-term tracking. Carbon dots (CDs) have high water solubility, low toxicity, photostability and phototunable fluorescent property which can be used in the areas of biosensing, bioimaging, light emitting device and drug delivery. Here, red fluorescent carbon dots (RCDs) were synthesized by microwave assisted pyrolysis of p-phenylenediamine (pPD). RCDs emitted at the wavelength of 635 nm when excited at 494 nm. The size of RCDs was 3.83 ± 1.25 nm analyzed by Atomic force microscopy. Little cytoxicity against mesenchymal stem cells (MSCs) was found at the concentration lower than 200 µg/mL. MSCs exhibited red fluorescence after 24-hour incuba-tion with RCDs. RCDs were further conjugated with hyaluronic acid (HA) by amide bond formation to produce HA-RCDs as verified by Fourier-transform infrared spectroscopy analysis. The size of HA-RCDs was increased to 5.47 ± 1.91 nm. The compari-son of MSCs labeling efficiency of RCDs and HA-RCDs will be investigated in vitro and in vivo in the near future.


Tai-Wei Feng, Quoc-Hue Pho, Ming-Fa Hsieh, Tzu-Chau Lin and Yueh-Ching Liu

We have synthesized a novel theranostic nano-carrier to encapsulate a two photon fluorescent dye, named as, 2QMEH, as a diagnostic molecule loaded in amphiphillic di-block copolymers, methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL for near infrared diagnostics in cancer treatment. Here in, the di-block copolymers, mPEG-PCL, with different molecular weights have been synthesized. Critical micelle concentrations (CMC) of mPEG-PCL copolymers were determined. A copolymer was selected as an optimal sample due to its highest loading efficiency of 2QMEH of 68.6 %. The encapsulation of 2QMEH loaded micelles showed significant two photon absorption (TPA) cross section of around ~55-120 GM (1 GM = 1 x 10 50 photon cm4 s photon-1 molecule-1) at 820 nm, which is immensely greater than the threshold value for biological applications. In addition, mPEG-PCL copolymer showed higher TPA cross section (120 GM) which may led the potential utility of these dyes encapsulated micelles for both conventional and two photon fluorescence-based in vivo bio-imaging and as well as near infrared diagnostics in cancer treatment.


che-yi chang, Zheng-Han Tsai, Guei-Sheung Liu, Peng-Yuan Wang and Ching-Li Tseng

Abstract— Eye is a closed organ with slow blood circulation; mostly, drugs can’t effectively reach the posterior segment of eye such as retina. Current treatment of drug delivery to reti-na is intravitreal injection. However, this invasive way with frequently injection often resulted in side effects for example hemorrhage, cataract, and retina detachment. Eye drops is the most commonly formulation for ocular drug delivery, but almost not possible to delivery drug to the retina. Nowadays, nanoparticles have been used to increase drug retention in ocular surface increasing drug bioavailability. The objective of this study is to develop a polysaccharide modified nanoparti-cles to enhance its delivery effect to retina by topical admin-istration, eye drops. C57BL/6 mice were used to evaluate the delivery effect of eye drop with nanoparticles. Image quantifi-cation of whole eyeball section was adapted, fluorescent signal of nanoparticles was traced in the eyeballs sections. In conclu-sion, more number of hyaluronic acid (HA)- modified nano-particles (NPs) with positive charge was founded in the retina. It shows the potential as an effective carrier for posterior ocu-lar drug delivery.


Chun-Hao Wu, Ming-Wei, Chao and Chia-Yi, Tseng

Mesenchymal stem cells (MSCs) are pluripotent cells that are present in multiple tissues, including bone marrow, adipose tissue, skin, muscle, blood, and placenta. It has been proved that MSCs can interact with cells of both the innate and adaptive immune systems, and thus act as a possible clinical therapy for immune-mediated diseases, such as osteogenesis imperfecta, severe graftversus-host disease (GvHD), and Crohn’s disease. Maternal bacterial infections during pregnancy represent a significant risk factor in preterm as well as neuropsychiatric disorders with a presumed neurodevelopmental deficit. One of the downstream syndrome, neuroinflammation, has been reported to be highly associated with numbers of neurological and pathological diseases, like schizophrenia, cerebral palsy, and autism. Epidemiological studies suggested that intrauterine infection acts as a crucial role in inducing neuroinflammatory response, which would lead to neurodegeneration and functional deficits in fetal brain, including area involved in learning and memory. However, the mechanism in abnormal fetal brain development remains largely unknown. The possible action of which in neuro inflammation-induced fetal brain damages is likely to be through cytokines and oxidative stress. Accordingly, we hypothesize that MSCs may attenuates intrauterine infection induced neurodevelopmental defects by modulating the inflammation response and oxidative stress. To address the question, lipopolysaccharide (LPS) administration is used to model clinical bacterial infection in pregnant animals. LPS and MSCs will be infused into pregnant rats intraperitoneally, and the cytokine and ROS production will be analyzed. To lable the neuron generation, BrdU was injected subcutaneously during gestation. Moreover, cortical laminate markers, such as Ctip2, Satb2, were labelled to investigate the migration events during brain development. We propose to see that the LPS -induced toxic outcome will be ameliorated in the presence of MSCs. In the first place, this study will describe the initial efforts to evaluate the likely therapeutic effects of MSCs on LPS-induced developmental failure.


Tse-Lin Hsu and Po-Lei Lee

Brain computer interface (BCI) system has been regarded as an emerging technology to provide an alternative pathway between human brain and external devices for disabled patients. The key issue of establishing a successful BCI system depends on the development of stable detection algorithms for EEG classifications. However, due to the complexity of brain signals, traditional machine learning methods might be incapable of interpreting the measured EEG signals and only achieved limited performances. Therefore, in this study, we adopted deep-learning methods to implement a dry-electrode EEG BCI system. EEG signals were measured from three sites, including C3, Cz and C4, according to international 10-20 montage system. Subjects were requested to perform left and right hands imagery movements. The measured EEG data were transformed into temporal-frequency domain using wavelet analysis, and signal features on temporal-frequency domain were used as input data to train a convolutional neural network for signal classifications. Our results has achieved detection accuracy over 74% which demonstrated the capability of the proposed system in future applications.


ChungHung Wang, Chi-Ming Ku, Chien-Hung Chang and Tzong-Rong Ger

Ischemic strokes account for 80% of all strokes and gold treatment time is a very important factor for ischemic strokes. Collateral status is an important determinant of clinical outcomes in ischemic stroke. Our goal is to develop a program for quantifying collat-eral parameter of ischemic stroke with multiphase computed tomographic angiography (CTA) images. Image processing and vas-cular parameter calculation were performed using a semi-automated analysis program. Patients were divided into three groups based on Modified Rankin Scale (mRS), which were good, intermediate, and poor groups. We had compared vessel density (VD)、skeleton density (SD) and vessel diameter index (VDI) with stroke and non-stroke half-brain. We found that the vessel morpholo-gy changes with time, and VD has the same trend, which may indicate that VD can be used to represent vascular changes. We found that the VDI with stroke of half-brain is always greater than non-stroke half-brain. VDI might be a good candidate to eval-uate side or ROI of stroke vessel. Thus, we have developed a semi-automatic program that can automatically process CTA images and quantify the vessels and vessel Parameters which might be meaningful to predict factors for stroke evaluation.


CHIA-CHI YANG, Pinyu Chen, Chia-Han Hu, Yan-Zhi Huang, Zong-Liang Zou, Yong-Jun Nian and Lan-Yuen Guo

Common drive describes a phenomenon in which almost all of the firing rates of motor units within the same muscle fluctuate in proportion to each other and is proposed to be the general strategy for increasing muscle force by the central nervous system. The present study aimed at determining if there was a difference in the common drive of the biceps brachii between athletes and non-athletes during isometric contractions. There was a total of 13 subjects in this study: 6 non-athlete subjects and 7 athletes. The athletes were made up of table tennis, badminton, and volleyball players. The subjects were initially asked to perform a maximum voluntary isometric contraction (MVC) and then isometric contractions at 25% and 50% of their MVC. Subsequently, the surface electrophysiological signals of the biceps brachii were decomposed into individual motor unit action potential trains and the strength of common drive between the firing rate fluctuations of pairs of concurrently active motor units was examined by cross-correlating their mean firing rate signals. As hypothesized, the present work found that the athletes had higher levels of correlation in pairs of concurrently active motor units as compared to non-athlete individuals. It is concluded that elevation in common drive for athletes was suggestive of central neural adaptive strategies


Nien-Che Liu, Kin-Fong Lei and I-Chi Lee

Recently, numerous in vitro studies about neurotoxicity of amyloid-beta have been published. However, to mimic a three-dimensional neuronal tissue model for study neurotoxicity of amyloid-beta still limited. In this study, a neurospheroids based network formation platform was designed and fabricated that able to control the differentiation of neural stem/progenitor cells (NSPCs), neurite direction, and to promote the neurite outgrowth. Microelectrode arrays with multi channels platform were fabricated to stimulate and determine the neuronal network development and organization. After robust neural network formation, this platform may provide the potential for studying the neurotoxicity of amyloid-beta and drug screening for neurodegenerative diseases.


Cheng-Hong Wang, Teng-Chi Tang, Ming-Shaung Ju and Chou-Ching K. Lin

Temporal lobe epilepsy is the most common form of partial epilepsy. Although drug therapy is widely used, there are one-third of patients whose seizures are not well controlled. So it is necessary to develop novel treatments to help these patients. The purpose of this study is to develop a control system to suppress acute seizures by integrating electrical and photic stimulations. Thy1-mhChR2-YEP transgenic mice were inject-ed with lithium and pilocarpine to induce acute seizure. Depth-EEG from hippocampus was acquired and the sample entropy was calculated and served as the input to the closed-loop con-trol system. An on-off control law for electrical stimulation and a piecewise proportional control law for photic stimulation were integrated in the control system. The results from 12 subjects show seizure recognition rate rose up to 92% in the acute stage. Both the electrical stimulation alone and the inte-grated electrical and photic stimulations could effectively sup-press seizures, with a suppression rate greater than 83.3%. The suppression rate of integrated electrical and photic stimu-lation was generally higher than that of electrical stimulation alone. At the same time, the average suppression time was increased by 1.47 seconds in the integrated stimulation system. In conclusion, integrated electrical and photic stimulations may provide a new direction of development on treating seizure in the future.


James Delaney Chen and Wen-tyng Li

Abstract— Electrospinning is a technique to fabricate micro- to nano-sized continuous fibers by drawing charged threads of polymer solutions using a high-voltage power supply. Electrospun fibers have the three-dimensional structure similar to extracellular matrix (ECM) which are beneficial to cell growth and differentiation. This study was aimed to investigate the effect of sciatic nerve repairing by the nerve conduits made of electrospun silica fibers. The diameters of random (R-SNFs) and aligned silica nanofibers (A-SNFs) were 414+104 and 363+103 nm, respectively. The surface contact angle of R-SNFs and A-SNFs were 29o. 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead fluorescence staining revealed that the adhesion and survival of rat bone marrow derived mesenchymal stem cells (MSCs) on R-SNFs and A-SNFs were higher than the control group. Nerve guidance conduit made of SNFs was implanted in rats to repair a 10 mm nerve gap after sciatic nerve transection. At four-week post-implantation, A-SNFs group showed better sciatic function index (SFI) compared to R-SNFs. The nerve compound action potential obtained by electrophysiology proved that the nerve conduction got through the SNFs implant gradually. The current positive results enable the application of these nerve conduits made of SNFs to be a potential strategy for the treatment of peripheral nerve injuries.


Ching-Ting Lin

Spinal cord injury (SCI) is a damage to any part of the spinal cord that changes in its function. SCI often causes permanent changes in strength, sensation or other body function, chronic pain, and some severe motor dysfunction such as neurogenic bladder dysfunction. This animal study is to find out the difference of bladder function after spinal cord lesion. Comparing the results of electromyography of external urethral sphincter (EUS-EMG) and analyze by self-made MATLAB program, we find out that the frequency of EUS-EMG is significantly decrease during the voiding cycle of the normal rats, but the SCI one does not. This may be a good method to detect the bladder dysfunction.