Polymeric Microfluidic Device

RT-LAMP PCR on µPADs

Paper-based microfluidic devices

3D Printed Microlens Array for High

Numerical Aperture

Research
Focus 3D Printed Microneedle

PDMS
substrate

3d Printed Microelectrode

Intraoperative Neuromonitoring

Artificial organ for surgical training

Maximizing Bonding Strength of PDMS/PMMA for Fabrication of High-Density
Microfluidic Devices
Purpose: PMMA/PDMS hybrid microfluidic device is popular for various applications, but the currently reported bonding strength between PMMA and PDMS limited the application of such hybrid
microfluidics. Therefore Taguchi method was applied to maximize the bonding strength by studying parameters such as chemical reagent concentration, plasma power, plasma time, and flow
rate of oxygen for plasma treatment. With the maximized bonding strength, the microfluidic devices with very high density is realized.

Novel Optimized Bonding Procedure

APTE
Oxygen
S Tensile test Burst test
plasma Contact of the substrates at 3000 kPa with water 622 kPa
Plasma treatment Surface modification room temperature with air 770 kPa
• Oxygen: 800 mTorr • GPTMS: 1%
• Power: 6.8 W • APTES: 3%
Oxygen • Time: 60 s GPTM • Time: 20 min
plasma S

Extremely strong bonded

PDMS-PMMA chip

Extremely high flow rate micropump with inertial microfluidics device for blood plasma
Applications extraction
High-density High-density microvalves
microchannels system

High separating efficiency

~97%
T.N.A. Vo, P.-C. Chen*, P.S. Chen, W.H. Liu, Sensors and Actuators A, 358, 2023, 114430 (SCI, IF: 4.291, Rank: 15/64, Q1).
T.N.A. Vo, P.-C. Chen*, Sensors and Actuators A, 334, 2022, 113330 (SCI, IF: 4.291, Rank: 15/64, Q1).
Developing a Vacuum-actuated Peristaltic Micropump (VPM) with Inclined Wall Design
to Achieve Low Hemolysis Blood Plasma Extraction
Purpose: We successfully developed a single integrated device for plasma separation without external pumps. The critical innovation used a vacuum actuator to prevent the membrane's effect
on RBCs. In addition, the obstacle wall of actuators was improved from a vertical wall to an inclined wall to prevent lysed of RBCs in the dead volume of the actuators. Then, a spiral trapezoidal
cross-section microchannel was directly bonded with VPM to make a fully microfluidic device rapidly extracting plasma from diluted blood using small volumes. The device performs blood
plasma separation with high efficiency (98.5%), quickly (<1 min), automatically, with minimal whole blood usage (5 µL), achieves very little hemolysis (<2%).
(a) (b) (c)
vacuum Flow
GPTMS
Mask Mask dicrection

PMMA PMMA PMMA

APTES (b-i)

PDMS PDMS
PMMA
90x 40x 20x
98.5% 96.5% 92.7%
Micro milling Oxygen plasma Surface modification
(a-i) (a-ii) (a-iii) (b-ii)

APTES (d) (e) (f)

PDMS-PMMA PDMS-PMMA (b-iii)

GPTMS

PMMA Vacuum-actuated peristaltic

PMMA
Surface modification micropump
Oxygen plasma (b-iv)
(a-iv) (a-v) (a-vi)

Figure 1: (a) Fabrication process of PMMA/PDMS/PMMA VPM;

(b) Working principle of VPM by applying vacuum pressure Figure 3: (a~c) Collected blood plasma at the outlet at dilution 90×, 40×, and 20× respectively;
(d) Picture of original sample dilution 90x (left), collected RBCs (center), collected plasma
whole blood (b) (c) (right); RBCs in collected solution under ×20 objective lens at: (e) RBCs outlet, (f) plasma
% Hemolysis in collected plasma outlet.
6.00 Figure 4: Evaluation of
Plasma
hemolysis in collected plasma
5.00 outlet with different dilution
Buffer
ratios and designs of the

Hemolysis (%)
(d) (e) 4.00
PMMA PMMA obstacle walls.
3.00

PDMS PDMS 2.00

On-chip micropump
(a) PMMA PMMA 1.00

0.00 Contribution:
Figure 2: (a) The preparation for blood plasma separation; Inclined wall Verticle wall Inclined wall Verticle wall Inclined wall Verticle wall IEEE MEMS 2024
(b-e) designs of the vertical and inclined obstacle walls. 90x 90x 40x 40x 20x 20x Best paper award ICSS 2023
3DP µ PADs column liquid chromatography-mass spectrometry (µ PC LC-MS) for detection
of abused drugs in human biofluids
Purpose: Paper spray ionization is a simple method to analyze samples by mass spectrometry (MS) without sample preparation. A stereolithography 3D printed microfluidic paper-based column
coupled to liquid chromatography-MS (µPC-LC-MS) was developed and offers several beneifts such as: (1) significantly extended the lifetime up to 50 minutes per run (2) Separation of three
psychoactive (4) high sensitivity (LOD between 0.5 and 1 ng/mL) and accuracy (87.0% to 109.1%), (5) high reliability with linearity from 5 to 500 ng/mL (R²) from 0.9925 to 0.9999 using only 1 µL
plasma.
Fabrication Process: 3D Print DLP Device Structure and Design

Detection Protocols: Ionization and Chromatography Analysis Results: Spray Performance and Drugs Chromatography

Water Urine Plasma

Drugs LOD Linear range R2 LOD Linear range R2 LOD Linear range R2
Methamphetamine 0.05 0.05 - 100 0.9994 0.1 0.5 - 100 0.9983 0.5 10 -1000 0.9999

M. F. Zaki, P. -C. Chen, Y. -X. Wu and P. -S. Chen, 2023 IEEE MEMS 2023 Munich, Germany, 2023, pp. 1052-1055. Morphine-3-G 0.05 10 - 500 0.9984 0.1 10 - 500 0.994 1 10 - 500 0.9945
7-aminonitrazepam 10 10 - 500 0.9925 100 100 - 500 1 1 1 - 1000 0.9973
M.F. Zaki, Y.X. Wu, P.C. Chen*, P.S. Chen*, Sensors and Actuators B: Chemical, , 393, 134243 (SCI, IF: 9.221, Rank: 2/64, Q1)
DNA Biomarker Detection: Utilizing Loop-Isothermal Amplification (LAMP) with µ PADs
and Closed-loop Temperature Sensors
Purpose: Loop-mediated isothermal amplification (LAMP) is an appealing method for affordable and on site nucleic acid diagnostic tests, owing to its high sensitivity, low equipment demands, and
compatibility with easy-to-use colorimetric detection methods. This paper explores the use of LAMP in conjunction with microfluidics paper-based analytical devices (µPADs) and a closed-loop
temperature sensor system to create a cost-effective temperature control system for detecting several bacterial DNA which could lead to a severe sickness.
µ PADs Fabrication process LAMP reaction design and detection

LAMP solution preparation Thermal distribution analysis using IR camera Closed loop temperature sensor device components
Integrating AI Optical Design to Fabricate Microlens Arrays with High Optical
Performance and Wide Applications
Purpose: Microlens arrays (MLAs) is an important optical component used in various emerging fields. In our previous studies, we have successfully demonstrated the rapid fabrication of MLAs
with low surface roughness and high image resolution by applying grayscale digital masks and defocusing method to digital light processing (DLP) stereolithography (SLA) 3D. To further improve
the performance of printed MLAs competitive to the commercial MLAs, our team integrate artificial intelligence (AI) optical design in conjunction with a new photopolymer specifically developed
for MLAs to optimize the parameters of printed MLAs. Experiment results clearly show that: (1) AI optical design enables the fabrication of MLAs with various profiles including high numerical
aperture, multiple focal lengths, high fill factor (77.98%), and low lens diameter (60 μm), (2) the combination of defocus method and newly developed photopolymer significantly reduced the
average surface roughness (Sa) of the printed MLAs to 80 nm, which is critical to the image resolution, (3) by integrating AI optical design, the image resolution was optimized to 58.7 lp/mm, which
is very competitive or superior than the commercial plastic MLAs with resolution of 48.8 lp/mm.
DLP-SLA 3D Printing System Image Resolution of MLAs Defocus Method

Without
defocus
100 μm

With
defocus
100 μm

MLAs with Lens Diameter of 60 μm MLAs with Multiple Focal Lengths MLAs with High Fill Factor (77.98%)

f = 22 μm f = 109 μm f = 200 μm
P.-C. Chen*, C.Y. Hsieh, " Sensors and Actuators A (SCI, IF: 4.291, Rank: 15/64, Q1, 2023).
P.-C. Chen*,C.S. Yeh, C. Y. Hsieh, Sensors and Actuators A, 345, 113819 (SCI, IF: 4.291, Rank: 15/64, Q1, 2022).
Microneedle Fabrication to Achieve Enhanced Surface Smoothness and Improved Size
and Shape Precision Using DLP
Purpose: This research used Digital Light Processing (DLP) for fabricating μNs which is able to print needle-like structures with diameters ranging from 100um to 445um and heights spanning
from 381um to 1500um. Machine learning (ML) is integrated for determining DLP printing parameters to avoid the unpleasant results (Fig. 1). ML model is configured as two inputs, five outputs,
and 10 hidden layers (Fig. 3). The accuracy (Acc) of ML model is achieved 96.84% by printing out the testing data and measuring the diameter. Figure 4a is showing the stair-effect in μNs
fabrication. The width of the stair is 5.88um within 1,500 times of magnification. The future goal of this research is trying to reduce the stair effect for a smooth surface.
Fig. 2 Flowchart of ML model.
𝐴𝑐𝑐
𝑁
1 𝐴𝑖 − 𝐺𝑖 (1)
= ෍ 100 − 100
𝑁 𝐴𝑖
𝑖=1

(a) (b)
Fig. 1. Top and side views of μNs w/o ML model

Fig. 4 μNs Fabrication.

(a) (b)

Fig. 5 Top view SEM image of μNs.

Fig. 3 ML model configuration.
Patterning Conductive Polymer for microelectrode on various substrate using Digital
Light Processing 3D printing
Purpose: Sensors play a crucial role in micro total analysis systems (µTAS) by detecting, analyzing, and processing samples within the chip. To be compatible with the microstructure of the device,
sensors need to be miniaturized. However, the current fabrication methods for miniaturized sensors are expensive, complex, and time-consuming, particularly when working with flexible
substrates. In this study, we propose a rapid and robust fabrication method for microelectrodes using 3D printing SLA DLP. This technique allows for printing on various substrates such as glass,
polymer (PDMS), and paper. The developed method demonstrates the capability to produce high-resolution microelectrodes with complex patterns while maintaining good electrical properties.
Material Preparation: CNT composite photo resin Fabrication: Single Exposure of UV light

Microelectrode on various substrate: Printing Parameters and Electrical Properties of Conducting Polymer
PMMA GLASS PDMS

5 mm 5 mm 5 mm

M. F. Zaki, C. F. Sun, and P. -C. Chen, The 37th International Conference on Micro Electro Mechanical Systems (IEEE MEMS) Austin, Texas, USA 2024.
Professional Medical Simulator for Neurosurgeon Trainees
Purpose: Neurosurgeon trainees face limited opportunities for hands-on experience in complex surgeries, necessitating the use of professional simulators. In this study, we employed additive
manufacturing, molding, elastic material casting, and ultrasonication-assisted dissolution to create a physical simulator for aneurysm clipping operations. Additionally, we integrated electronic
engineering technology to develop a simulator with a signal feedback system for training neurosurgeons in tumor removal from the spinal cord while avoiding motor nerve contact. This holistic
approach aims to enhance the practical skills of neurosurgeon trainees and provide a more immersive learning experience.. (Video Link: https://youtu.be/QtKxDN8Rz5w &
(d)
https://youtu.be/riDS3ha4yXQ) Piezoresistive Device (motor nerve model)
Aneurysm
Anterior Cerebral Base layer composite method (spraying)
Artery (ACA)
Aneurysm
Anterior Surgical Forceps Brain Lobes
Communicating
Artery (AComA)
conductive layer
Middle Cerebral
Artery (MCA) Internal Carotid Artery Insulation
(ICA)
Posterior
Communicating
Artery (PComA) Posterior Cerebral
Artery (PCA) Spinal Cord
Aneurysm (Central Nervous System)
(f)

Tumor Spine
Meninges
Brain Lobe
(Best Paper Award) P.C. Chen*, C.-H. Chiang, “Creating A Lifelike Willis Circle Simulators with Cerebral Aneurysms for Training Brain Neurosurgery”, 23 rd Nano Engineering and Microsystem Technology Conference,2020/10/19-20, National
Sun Yat-Sen University, Kaohsiung, Taiwan.
P.C. Chen, J.C. Lin, C.H. Chiang, Y.C. Chen, J.E. Chen, W.H. Liu*, "Engineering Additive Manufacturing and Molding Techniques to Create Lifelike Willis’ Circle Simulators with Aneurysms for Training Neurosurgeons", Polymers, 12, 2901,
2020 (SCI, IF: 3.426, Rank: 16/89, Q1).