An evaluation of a real-time passive micromixer to the performance of a continuous flow type microfluidic reactor

Pin-Chuan Chen 한국바이오칩학회 2013 BioChip Journal Vol.7 No.3

Microfluidics has been developed as an important platform for biochemical/chemical reactions. How to enhance the performance of a microfluidic chemical reactor is one of the core concerns when designing the microfluidic device. In the pressure-driven microfluidics without micromixer, parabolic flow profile dominates the behaviors of the laminar flow as well as the reaction particles such as DNA fragments, proteins, and enzymes. The aim of this study is to elucidate and answer a question: does a groove-shape passive micromixer improve the performance of a continuous flow type microfluidic reactor? Two mold inserts were micro-milled in the experiments, one had regular microchannels and the other one had regular microchannels with groove-shape passive micromixers, and both polymeric chips were manufactured with hot embossing techniques. Multiple experiments were realized on both chips to evaluate the groove-shape passive mixer to the performance of a continuous flow type microfluidic reactor. Polymerase chain reaction (PCR) is a typical example of chemical reaction in microfluidics, a 99 bp DNA fragment from λ-DNA was used as the target in the experiments. In this study,multiple experiments were carried out, analyzed, and concluded that the groove-shape passive mixing is not beneficial to the performance of a continuous flow type microfluidic reactor. The results showed that a regular microfluidic device without mixing had better amplification efficiency of the target DNA fragments, which indicated that using a real-time passive mixing component inside a continuous flow environment, increasing the chance of protein absorption and strengthening shear force to molecules, might cause the negative impact to the PCR reaction performance.

Systematically Studying Dissolution Process of 3D Printed Acrylonitrile Butadiene Styrene (ABS) Mold for Creation of Complex and Fully Transparent Polydimethylsiloxane (PDMS) Fluidic Devices

Chen Pin-Chuan,Chou Ching Chan,Chiang Chung Hsuan 한국바이오칩학회 2021 BioChip Journal Vol.15 No.2

Our major objective in this study was to create complex, three-dimensional, and fully transparent polydimethylsiloxane(PDMS) fluidic device by revising the previously reported fabrication process and to systematically study the influence of each fabrication step to the final PDMS fluidic device. The current fabrication process adopted fused deposition modeling (FDM) 3D printers to create molds of acrylonitrile butadiene styrene (ABS) for use in PDMS casting, then solvent solution was used to dissolve the ABS mold embedded inside the PDMS device and a transparent PDMS device was created for experiments. However, it is quite challenging to ensure the complete removal of ABS molds inside the long, curly, and narrow channels. Ultrasonication was added into our fabrication process to improve the efficacy of dissolving ABS molds inside the channels and conclusions can be derived from these experiments: (1) ultrasonication-assisted dissolution is an effective approach to the complete removal of ABS molds embedded inside these long, curly, and narrow channels (for example, the mixer demonstrated herein had a diameter of 2 mm and length of 162 mm); (2) the application of solvent vapor polishing to 3D-printed molds is highly effective in reducing the surface roughness of the molds (8 ~ 10 μm before polishing to 038 ~ 0.5 μm after polishing) and important to preserve the transparency of the resulting PDMS devices; (3) ensuring the circulation of fresh solvent solution is critical to shorten the dissolution process.

Design and Characterization of a Capillary-Driven and Parallelized Microfluidic Chip for Distributing a Liquid Plug

Pin-Chuan Chen,Yan-Fong Cheng,Kung-Chia Young,Hung-Lin Hsieh,Chin-Lung Yang 한국정밀공학회 2016 International Journal of Precision Engineering and Vol.17 No.11

To realize a portable, capillary-driven, and parallelized microfluidic chip, how to evenly distribute a liquid plug from the inlet to multiple daughter microchannels is a challenging task. Two approaches were adopted to generate sufficient capillary pressure to allow a liquid plug spontaneously flowing through bifurcation features, including enlarging the contact perimeter between the liquid plug and microchannel walls and applying hydrophilic coating to the microchannel walls. A 1-to-2 bifurcation microfluidic chip and a 1-to-4 bifurcation microfluidic chip were designed and fabricated on PMMA substrates for experiments. Initially red food dye was used to demonstrate the effectiveness of the chips, and experiment results revealed that the 1-to-2 microfluidic chip is capable of 100% liquid splitting efficiency with a CV of 5.7% whereas the 1-to-4 microfluidic chip is capable of 83% liquid splitting efficiency with a CV of 6.7%. After successfully conducting experiments with red food dye, human whole blood and blood plasma were introduced into the 1-to-2 microfluidic chips and splitting efficiency was investigated. The experiment results showed a 33% and 67% splitting efficiency for human whole blood and blood plasma, respectively. And the lower splitting efficiency can be attributed to the complex and Non-Newtonian fluidic property of the blood.

Parameter Optimization of Micromilling Brass Mold Inserts for Microchannels with Taguchi Method

Pin-Chuan Chen,Yu-Chieh Chen,Chang-Wei Pan,Kuan-Ming Li 한국정밀공학회 2015 International Journal of Precision Engineering and Vol. No.

Achieving excellent quality of micromilled surfaces usually requires additional efforts and cost, and Taguchi methodology is anefficient tool in the parameter optimization process. The aim of this study is to explore the optimal cutting parameters for minimalsurface roughness of a micromilled brass mold inset, and the controlling parameters included coolant, spindle speed, feed rate, depthof cut, and the stepover. An orthogonal array and factor analysis were carried out to identify the optimal cutting combination, andthis combination included air coolant, spindle speed of 45,000 rpm, feed rate of 100 mm/min, stepover of 10% of milling bit diameter,and the depth of cut of 5 μm. To further confirm the analysis, multiple confirmation runs were realized and the averagely measuredsurface roughness was 0.03 μm with a stand deviation of 0.004 μm.

Optimization of Micromilling Microchannels on a Polycarbonate Substrate

Pin-Chuan Chen,Chang-Wei Pan,Wei-Chen Lee,Kuan-Ming Li 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Rapidly prototyping a polymer microfluidic device is a growing interest for various applications and micromilling is one of the common approaches to manufacture polymer microfluidic devices. The advantages of using micromilling for polymer microfluidic devices include shorter fabrication process, lower cost, easier user interface, and being capable of fabricating complicated structures, which make micromilling a perfect tool in research idea testing and validation. The aim of this study is to understand the impact of each micromilling parameter to the surface roughness on a polycarbonate substrate, followed by the factor analysis to determine the optimal cutting conditions. The parameters included spindle speed, feed rate, and the depth of cut, and the roughness was measured by a stylus profilemeter. The smallest roughness achieved was 0.127 µm with the spindle speed of 20,000 rpm, feed rate of 300 mm/min, and the depth of cut of 10 µm. Factor analysis was used to determine that the spindle speed has the largest impact while the depth of cut has the minimized impact to the surface quality. To further confirm the optimal cutting conditions, twelve reservoirs were micromilled with the optimal cutting conditions and the average roughness is 0.14 µm with a stand deviation of 0.08 µm.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.