Tsung‐Tao Huang

National Applied Research Laboratories

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Junsheng Wang

Dalian Maritime University

Yu-Hsiang Tang

National Applied Research Laboratories

Ming‐Hua Shiao

National Applied Research Laboratories

Sheng‐Tung Huang

National Taipei University of Technology

Chih‐Sheng Yu

National Applied Research Laboratories

Yin‐Kai Chen

Mansoura University

Yih‐Jen Hsu

National Taiwan University Hospital

Chun‐Yu Chuang

National Tsing Hua University

Chih‐Hung Huang

National Taipei University of Technology

Yu-Hsin Lin

West China Medical Center of Sichuan University

Cooperative Institutions

National Taiwan University

National Applied Research Laboratories

National Tsing Hua University

National Yang Ming Chiao Tung University

China Medical University

National Taipei University of Technology

National United University

National Chung Hsing University

China Medical University Hospital

Chang Gung University

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Real-Time Electrochemical LAMP for DNA Detection of Salmonella SPP

Tsung‐Tao Huang Yu-Hsiang Tang Junsheng Wang Yimei Lin Sheng‐Tung Huang

It is important to have clinical testing tools for food safety testing, forensic analysis, homeland security and environmental monitoring in recent years. How to rapidly and accurately find infected pathogens in a limited resource environment is an important topic. In the remote areas of genotoxic infection, Salmonella is one of the most common food borne pathogens. Rapid and accurate identification of Salmonella from food samples by public health agencies and diagnostic laboratories enable better to product quality and effective in preventing outbreaks of infection. In the research, we have developed an electrochemical platform with real-time monitoring LAMP of Salmonella spp. genomic DNA in foods. We have determined 30μM methylene blue (MB) as DNA intercalating redox probes to optimal concentration in the LAMP reaction buffer. Then, we have evaluated and valuated the real-time electrochemical LAMP assay for serial dilutions of Salmonella spp. comparing to fluorescence method. Their corresponding melting curves were also implemented. In the electrochemical and fluorescence LAMP, a detection limit as 1 DNA copy of the Salmonella DNA target was achieved in a reaction time less than 30 min.

Methylene blue

10.1109/nems.2018.8556893

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A parametric study of ICP-RIE etching on a lithium niobate substrate

Chun-Ming Chang Chih‐Sheng Yu Fan-Chun Hsieh Chun-Ting Lin Tsung‐Tao Huang

Z-cut LiNbO ₃ single crystal wafers were etched by the inductively coupled plasma reactive ion etching (ICP-RIE) technique by using the boron trichloride (BCl ₃ )/ Argon (Ar) mixture gases. Effects of the ICP power and RF power ranged from 100 W to 700 W of the ICP-RIE system were studied on the etching rate, surface roughness, and corresponding DC bias under different working pressures ranged from 10 mTorr to 50 mTorr, respectively. Besides, photoresist, Cr(20%)/Ni(80%) alloy and Ni thin films were used as the etching mask, and the selective ratios of the three etching masks were also compared. The surface roughness of the etched LiNbO ₃ substrate was increased when the ICP power and RF power were increased. The etching rate of the LiNbO ₃ substrate was increased with increasing the ICP power and RF power. It is noted that the etching rate was greater than 100 nm/ min when the working pressure was controlled at 30 mTorr. The selective ratios of the photoresist Cr/Ni and the nickel were calculated to be approximately 0.4, 7, 9, respectively. Under suitable processing parameters of ICP-RIE, the surface roughness less than 40 nm, structure depth greater than 3 μm, and sidewall angle is estimated to be 120° of the LiNbO ₃ substrate can be obtained within 28 min, which etching rate is greater than 117 nm/ min.

Photoresist

10.1109/nems.2015.7147473

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A Sensitive Ratiometric Long-Wavelength Fluorescent Probe for Selective Determination of Cysteine/Homocysteine

Journal of Fluorescence (2016)

Kesavan Manibalan Sin-Ming Chen Veerappan Mani Tsung‐Tao Huang Sheng‐Tung Huang

Naked eye

10.1007/s10895-016-1844-x

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Bisphenol A-induced DNA damages promote to lymphoma progression in human lymphoblastoid cells through aberrant CTNNB1 signaling pathway

iScience (2021)

Yin‐Kai Chen Yanyan Tan Min Yao Ho-Chen Lin Mon-Hsun Tsai

Lymphoma is a group of blood cancers that develop from the immune system, and one of the main risk factors is associated with exposure to environmental chemicals. Bisphenol A (BPA) is a common chemical used in the manufacture of materials in polycarbonate and epoxy plastic products and can interfere with the immune system. BPA is considered to possibly induce lymphoma development by affecting the immune system, but its potential mechanisms have not been well established. This study performed a gene-network analysis of microarray data sets in human lymphoma tissues as well as in human cells with BPA exposure to explore module genes and construct the potential pathway for lymphomagenesis in response to BPA. This study provided evidence that BPA exposure resulted in disrupted cell cycle and DNA damage by activating CTNNB1, the initiator of the aberrant constructed CTNNB1-NFKB1-AR-IGF1-TWIST1 pathway, which may potentially lead to lymphomagenesis.

Lymphoblast

10.1016/j.isci.2021.102888

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Enzymeless Flow Injection Analysis of 2,4,6-Trichlorophenol Based on Preoxidation by Ammonium Cerium (IV) Nitrate

International Journal of Electrochemical Science (2012)

Junsheng Wang Pei-Yen Chen Tsung‐Tao Huang Meng‐Shan Lin

Enzymeless flow injection analysis of 2,4,6-trichlorophenol (2,4,6-TCP) based on preoxidation by ammonium cerium (IV) nitrate will be presented in this work. A preoxidation scheme is applied for 2,4,6-TCP determination without any enzyme treatment. This preoxidation scheme can provide a determination method with low cost and non-conductive polymerization reaction of 2,4,6-TCP. In proposed scheme, the 2,4,6-TCP is oxidized to 2,6-dichloro-1,4-benzoquinone by ammonium cerium (IV) nitrate and the 2,6-dichloro-1,4-benzoquinone can be detected at low reduction potential. The linear range of 2,4,6-TCP determination was 0.4 to 750 M with correlation coefficient (R2) 0.9999 and the estimated detection limit (S/N=3) was 40 nM which were demonstrated by flow injection analysis. Twenty successive detect of 100 M 2,4,6-TCP showed the relative standard deviation was 1.56%. Several 2,4,6-TCP structure-like compounds were studied as interferences including 2,4- dichlorophenol, 2-chlorophenol, phenol and 4-aminophenol. No obviously influences were observed. Two water samples which were collected from local farm and pool were adopted as analytical application. The recoveries of two water samples are 105.2% and 107.5%, respectively. An easy operation and enzymeless treatment detection scheme of 2,4,6-TCP is illustrated in this work.

Flow injection analysis

Relative standard deviation

Ammonium nitrate

Linear range

10.1016/s1452-3981(23)16184-0

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Development of micro-needle array for Tumor vaccine patch applications

Yu-Hsiang Tang Yu-Hsin Lin Tsung‐Tao Huang Junsheng Wang Yi-Chiuen Hu

Microneedles have been given sufficient potential as a patch for transdermal drug delivery. However, very few product on the application of MEMS for the vaccine delivery is reported. The aim of this paper is to develop the vaccine coated solid microneedle patch by the use of micro-electromechanical systems (MEMS) technology, The fabrication of a silicon microneedle arrays made by UV lithography, inductively coupled plasma reactive ion etching (ICP-RIE) and wet chemical etching process. To solve the limitation of low vaccine volume carried, groove and pocket structure will be introduced. Besides, through the control of formulation of surface tension, viscosity and hydrophilic/ hydrophobic properties by optimization of vaccine formulation composition, the vaccine carried volume can be achieved. Moreover, bioactive of vaccine will be investigated by parameter of the osmotic pressure and phase-transformation. Combination of vaccine formulation and microneedle to fabricate the delivery device, the release profile of the device will be evaluated in vitro, and will be further evaluated in the artificial human skin system to observe the immune response. The research will be included two parts: 1. vaccine coated solid microneedle patch device will be established; 2. design a microneedle patch having specific application, such as enterovirus 71 vaccines, and to realize a commercial available vaccine microneedle patch device. Consequently, a microneedle array with biodegradable porous tips was further developed based on the fabricated microneedles patch.

10.1109/nano46743.2019.8993929

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Metal-enhanced fluorescence through conventional Ag-polyethylene glycol nanoparticles for cellular imaging

RSC Advances (2023)

Chih‐Jung Chen Chun-Yen Wu Chi‐Wei Wu Ching‐Wen Chang Tsung‐Tao Huang

A novel application of conventional Ag nanoparticles (NPs) for metal-enhanced fluorescence (MEF) in cellular imaging is proposed. Different molecular weights of polyethylene glycol (PEG) were tested to determine a suitable spacer on Ag NPs for MEF, and NPs comprising Ag with PEG with a molecular weight of 6000 g (Ag-PEG6k), when present in fluorescein solution, were discovered to cause a 2-fold quantum yield enhancement. For fluorescence imaging of mesenchymal stem cells stained by Alexa Fluor 488, the enhancement factor increased with the Ag-PEG6k NP concentration but decreased with the Alexa Fluor 488 concentration. At 243 parts per billion Ag-PEG6k NPs and 625 parts per million Alexa Fluor 488, the enhancement factor reached its greatest value of over 4.

10.1039/d3ra02277c

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The Effect of Azithromycin Plus Zinc Sulfate on ACE2 Expression through IκBα of Human Respiratory Cells in SARS-CoV-2: In Vitro Study

COVID (2021)

Chia-Wei Chang Ming‐Cheng Lee Bor‐Ru Lin Yen-Pei Lu Yih‐Jen Hsu

Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccines have been extensively distributed for global inoculation based on accelerated approval. With concerns of emerging spike protein mutations, we revisited the early but inconclusive clinical interest in the repurposed combination of azithromycin (AZT) and zinc supplements with safety advantages. The aim of this study is to provide in vitro proof of concept for IκBα associated rapid and synergistic suppression of angiotensin-converting enzymes 2 (ACE2) following combination treatments with AZT plus zinc sulfate in two human airway cells with ACE2 expression, Calu-3 and H322M, representative cells of the human upper and lower airway origin respectively. Clinical timing of AZT combined with zinc is indicated based on suppression of the key cellular entry molecule, ACE2, of SARS-CoV-2.

10.3390/covid1010021

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Investigation of fabricated Through Glass Via (TGV) process by inductively coupled plasma reactive ion etching of quartz glass

Yu-Hsiang Tang Yu-Hsin Lin Tsung‐Tao Huang Junsheng Wang Ming‐Hua Shiao

In this paper, we report the fabrication process of Through Glass Via (TGV) structure and basic design rules for glass based Three-Dimensional Integrated Circuit (3D-IC) packaging as well as a process flow for glass interposer applications. Quartz glass materials have been widely used in many packaging applications for micro electromechanical systems (MEMS), optical devices, and biomedical chips. Our work focuses on a 3D-IC package approach based on the use of thin glass as a substrate material. For through-glass-vias, holes were etched in glass wafers by photolithography and inductively coupled plasma-reactive ion etching (ICP-RIE) technologies and evaluated. The results of fabrication of TGV morphology showed a very good compromise between wafer thickness, TGV shape and via diameter for vertical interposer with 50 μm diameters in 150 μm thin quartz glass wafer still very stable for thin wafer processing without complicated processes.

Interposer

Deep reactive-ion etching

Dry etching

10.1109/nems.2015.7147453

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Development and Application of Novel Microfluidic Culture Chips for Germ Cells

Tsung‐Tao Huang Yu-Hsiang Tang Ming‐Hua Shiao Hung‐Wei Liu

This program is to improve the traditional germ cell culture technology, and expected to develop and validate the innovative germ cell microfluidic culture technology. The main concept is to use the in vitro microfluidic chip to mimic the fluid growth environment in the living body, and to shape the growth environment of the zygote cells into a bionic concept in the uterus. The main objective is to design to the most suitable growth conditions, the importance of which is to increase the chance of zygote cell culture to maturity and greatly improve the maturity of zygotic cells. Assist Reproductive technology is a related technology for in vitro washing, culturing and storage of human germ cells. The main method is to use an artificial culture medium that mimics the human body fluid of the human reproductive system to perform in vitro washing, culture, and storage of reproductive gametophytic cells. The project will be divided into three parts: 1. Bionic microfluidic chip design and production; 2. Biocompatibility and materialization analysis; 3. Germ cell chip efficacy verification. Therefore, this project will develop a continuous microfluidic chip, using a continuous microfluidic channel to simulate the growth of human germ cells in the fertility tube to the zygotic germ cell growth environment, and hope to improve the artificial reproductive technology success rate and pregnancy rate. Reduce the cost of repeated artificial reproduction, and eventually, develop into medical-grade products and promote local technology to the international market.

Lab-on-a-Chip

10.1109/nano46743.2019.8993901

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