Research 

1. Microfluidics that integrating electrical sensors for whole blood and bacterial analysis

Whole blood analysis reveals crucial information about physiological and pathological conditions. However, its complex composition requires tedious sample preparation steps. To simplify the above processes and reduce sample volume and reaction time, we integrated microfluidics with electrical sensors for on-chip whole blood processing and in-situ analysis. One example is developing a microfluidic device to simultaneously extract plasma, RBCs cells, and on-chip WBCs trapping (Sci Rep, 2018). Other examples are a vertical microfluidic device for plasma extraction and C-reactive protein detection (MicroTAS, 2021) and integrating a filter membrane on the DG-ISFET for on-chip bacteria enrichment and analysis (Sens. Act. B, 2022). We also did a comprehensive literature review to summarize the state-of-art techniques of using electrical sensors for whole blood analysis (Anal. Methods, 2020). 

Reference: 

1. Chia-Yu Hsieh and Nien-Tsu Huang*, “A proton-selective  membrane (PSM)-deposited dual-gate ion-sensitive field-effect transistor (DG-ISFET) integrating a microchamber-embedded filter membrane for bacterial enrichment and antimicrobial susceptibility test”, Sensors and Actuators B: chemical, 359, 131580, 2022. (Fields: Instruments & Instrumentation: 3/64, SCI, Impact Factor: 7.46) Link

2. Da-Han Kuan, and Nien-Tsu Huang*, “Recent advancements in microfluidics that integrate electrical sensors for whole blood analysis”, Analytical Methods, 12, 3318 - 3332, 2020/06. (Fields: Spectroscopy: 13/42, SCI, Impact Factor: 2.60) Link

3. Da-Han Kuan, et. al., “A Microfluidic Device for simultaneous Extraction of Plasma, Red Blood Cells and on-chip White Blood Cell Trapping” Scientific Reports, Volume 8, Issue 1, pp. 15345, 2018/10. (Fields: Multidisciplinary science: 12/64, SCI, Impact Factor: 4.12) Link

2. The integration of microfluidics with surface-enhanced Raman scattering (SERS)

Antimicrobial susceptibility testing (AST) is a standard laboratory procedure that evaluates the antibiotic resistance of bacteria. However, the current AST usually requires labor-intensive sample preparation steps. Dr. Huang’s group developed various microfluidics integrating SERS substrate to perform rapid, sample-efficient, and fully-integrated SERS-AST platforms, which help physicians monitor patients’ conditions and provide timely treatments. For example, we developed a microfluidic microwell array to increase the detection throughput (Lab Chip, 2020). Using the automated microfluidic control system, he integrated all sample processes, including bacteria encapsulation, antibiotic concentration generation, washing, and SERS measurement, into a single device (Biosens. Bioelectron., 2021). Lastly, he reported an antibiotic concentration gradient microfluidic device to perform multiplex AST (Lab Chip, 2022).

Reference: 

1. Shang-Jyun Lin, et. al., “An antibiotic concentration gradient microfluidic device integrating surface enhanced Raman spectroscopy for multiplex antimicrobial susceptibility testing”, Lab on a Chip, 22, 1805-1814, 2022 (Fields: Biochemical research methods: 7/78, SCI, Impact Factor: 6.80)

2. Cheng-Chieh Liao, et. al., “A microfluidic microwell device operated by the automated microfluidic control system for surface-enhanced Raman scattering-based antimicrobial susceptibility testing” Biosensors and Bioelectronics, 2021, 113483. (Fields: Chemistry, analytical: 3/83, SCI, Impact Factor: 10.62) Link

3. Hsiu-Kang Huang, et. al., “Bacteria Encapsulation and Rapid Antibiotic Susceptibility Test Using a Microfluidic Microwell Device Integrating Surface-enhanced Raman Scattering”, Lab on a Chip, 20, 2520 - 2528, 2020/06. (Fields: Biochemical research methods: 6/72, SCI, Impact Factor: 6.91) Link

3.  Localized Surface Plasmon Resonance (LSPR) biosensor

LSPR has become a widely-applied nanoplasmonic sensing technique based on its high sensitivity, miniaturized area, and simplified optical setup. Dr. Huang works on utilizing micro/nanofabrication techniques to fabricate sensitive and large-area LSPR substrates and microfluidics integration. We developed the rapid thermal annealing (RTA) process to generate centimeter-scale Au nanostructures for multi-point biosensing. By integrating the LSPR sensor with four-channel microfluidics operated by the automated microfluidic control system, IgG, CRP, and TNF-α mixture can be simultaneously detected (Analyst, 2020). Another LSPR fabrication method is using Aluminum Anode Oxide (AAO) as a template to fabricate uniform LSPR nanostructures. Since the period, gap, and diameter of the AAO template can be adjusted, the plasmonic coupling effect can be studied to improve LSPR sensitivity (ICSS, 2020).

Reference: 

1. Yang, C.-H.; Wu, et. al. Biosensing Amplification by Hybridization Chain Reaction on Phase-Sensitive Surface Plasmon Resonance. Biosensors 2021, 11, 75. (Fields: Chemistry, analytical: 15/83, SCI, Impact Factor: 5.52) Link

2. Pin-Fan. Chen, and Nien-Tsu Huang, “Nanoplasmonic Sensor Fabricated by Electron Beam Lithography Integrated with Automated Microfluidic System for Biomolecule Detection”, ICSS conference, Kaohsiung, Taiwan, October 19 to 20, 2020.

3. Jhih-Siang Chen, et. al., “A Localized Surface Plasmon Resonance (LSPR) sensor integrated automated microfluidic system for multiplex inflammatory biomarker detection”, Analyst, 145, 7654 - 7661, 2020/08. (Fields: Chemistry, analytical: 15/86, SCI, Impact Factor: 3.98) Link

4. H. T.-H. Lin, et. al., “A Large-Area Nanoplasmonic Sensor Fabricated by Rapid Thermal Annealing Treatment for Label-Free and Multi-Point Immunoglobulin Sensing” Nanomaterials, 7(5), pp. 100; 2017/05 (Fields: Materials science: 58/275, SCI, Impact Factor: 3.55) Link

4. A microfluidic device for single cell trapping and analysis: 

We aim to use microfluidics to enable single cell trapping and analysis. For example, we developed a microfluidic microwell device integrating a permanent magnet for on-chip immunomagnetic single cell trapping. By adding a microwell layer between the microchannel and magnet, the magnetic field along the device becomes more uniform. Besides, We developed a microfluidic device integrating super-resolution microscopy to perform flow stimulations followed by an in-situ fixation process to preserve primary cilium phenotypes and observe cilium-specific protein redistribution (Biomicrofluidics, 2019). The microfluidic system enables precise flow control and a well-confined cell culture environment. Besides, in-situ cilia fixation is feasible by instantaneously switching from the culture medium into the fixation buffer. The work utilized super-resolution microscopy to observe the movement of two cilium-specific proteins, acetylated alpha-tubulin (ac-α-tubulin) and intraflagellar transport protein 88 (IFT88) under flow shear.

Reference: 

1. Sheng-Han Chu, et. al., “A microfluidic device for in situ fixation and super-resolved mechanosensation studies of primary cilia”, Biomicrofluidics, 13, 014105, 2019. (Fields: Physics, Fluids & Plasmas: 10/31, SCI, Impact Factor: 2.57) Link

2. N.-T. Huang*, Y. J. Hwong, R. L. Lai, “A microfluidic microwell device for immunomagnetic single-cell trapping” Microfluidics and Nanofluidics, 22:16, 2018. (Fields: Instruments & Instrumentation: 17/58, SCI, Impact Factor: 2.34) Link

Last edit 2023/03