• Genomics & Informatics
• /
• v.19 no.1
• /
• pp.2.1-2.10
• /
• 2021

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

• Current Optics and Photonics
• /
• v.7 no.2
• /
• pp.119-126
• /
• 2023

The vibratory and rotational levels of many biological macromolecules lie in the terahertz (THz) band, which means that THz techniques can be used to identify and detect them. Moreover, since the biological activity of most biomolecules only becomes apparent in aqueous solution, we use microfluidic technology to study the biological properties of these biomolecules. THz time-domain spectroscopy was used to study the THz absorption characteristics of graphene oxide (GO) aqueous solution at different concentrations and different exposure times in fixed electric or magnetic fields. The results show that the spectral characteristics of the GO solution varied with the concentration: as the concentration increased, the THz absorption decreased. The results also show that after placing the solution in an external electric field, the absorption of THz first increased and then decreased. When the solution was placed in a magnetic field, the THz absorption increased with the increase in standing time. In this paper, these results are explained based on considerations of what is occurring at the molecular scale. The results of this study provide technical support for the further study of GO and will assist with its improved application in various fields.

• Journal of the Korean Society for Precision Engineering
• /
• v.33 no.1
• /
• pp.63-67
• /
• 2016

We present a method of fabricating poly (lactic-co-glycolic acid) (PLGA) porous microfibers using a pore template. PLGA microfibers were synthesized using a glass capillary tube in a poly-(dimethylsiloxane) (PDMS) microfluidic chip. Gelatin solution was used as a porous template to prepare pores in microfibers. Two phases of PLGA solutions in different solvents-DMSO (dimethyl sulfoxide) and DCM (dichloromethane)-were used to control the porosity and strength of the porous microfibers. The porosity of the PLGA microfibers differed depending on the ratio of flow rates in the two phases. The porous structure was formed in a spiral shape on the microfiber. The porous structure of the microfiber is expected to improve transfer of oxygen and nutrients, which is important for cell viability in tissue engineering.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.4
• /
• pp.1175-1180
• /
• 2013

A microfabricated electrochemical cell comprising PDMS-based microchannel and in-channel gold microelectrodes was fabricated as a sensitive and a miniature alternative to the conventional electroanalytical systems. A reproducible fabrication procedure enabled patterning of multiple microelectrodes integrated within a PDMS-based fluidic network. The active area of each electrode was $200{\mu}m{\times}200{\mu}m$ with a gap of $200{\mu}m$ between the electrodes which resulted in a higher signal to noise ratio. Also, the PDMS layer served the purpose of shielding the electrical interferences to the measurements. Analytes such as potassium ferrocyanide; amino acid: cysteine and nucleoside: guanosine were characterized using the fabricated cell. The microchip was comparable to bulk electrochemical systems and its applicability was also demonstrated with flow injection based rapid amperometric detection of DNA samples. The device so developed shall find use as a disposable electrochemical cell for rapid and sensitive analysis of electroactive species in various industrial and research applications.

• 한국정보디스플레이학회:학술대회논문집
• /
• 2009.10a
• /
• pp.1272-1273
• /
• 2009

We demonstrate conformal phosphor coating and patterning methods on light emitting diodes (LEDs) using image processing based optofluidic maskless lithography (IP-OFML) system in microfluidic channels. IP-OFML allows a real-time detection and dynamic mask generation for packaging of randomly dispersed microchips. Our system detects each chip by considering rotation of the chip through image processing regardless of their arrangement error. Therefore, it precisely packages the chip making conformal polymer layer.

• Korean Chemical Engineering Research
• /
• v.48 no.4
• /
• pp.470-474
• /
• 2010

In this study, we presents a simple microfluidic approach for generating uniform Poly(ethylene glycol)(PEG) microfiber. Elongated flow pattern of monomer induced by sheath flow of immiscible oil as continuous phase is generated in Y-shape junction and in situ polymerization by UV exposure. For uniform microfiber, we investigate the optimized flow condition and draw phase diagram as function of Ca and Qd. At the region for stable elongated flow pattern, the microfiber generated in microfluidic chip is very uniform and highly reproducible. Importantly, the thickness of microfibers can be easily controlled by flow rate of continuous and disperse phase. We also demonstrate the feasibility for biological application as encapsulating FITC-BSA in PEG microfiber.

• Design & Manufacturing
• /
• v.15 no.2
• /
• pp.11-16
• /
• 2021

Recently, three-dimensional (3D) cell culture systems, which are superior to conventional two-dimensional (2D) vascular systems that mimic the in vivo environment, are being actively studied to reproduce drug responses and cell differentiation in organisms. Conventional two-dimensional cell culture methods (scaffold-based and non-scaffold-based) have a limited cell growth rate because the culture cannot supply the culture medium as consistently as microvessels. To solve this problem, we would like to propose a 3D culture system with an environment similar to living cells by continuously supplying the culture medium to the bottom of the 3D cell support. The 3D culture system is a structure in which microvascular structures are combined under a scaffold (agar, collagen, etc.) where cells can settle and grow. First, we have manufactured molds for the formation of four types of microvessel-mimicking chips: width / height ①100 ㎛ / 100 ㎛, ②100 ㎛ / 50 ㎛, ③ 150 ㎛ / 100 ㎛, and ④ 200 ㎛ / 100 ㎛. By injection molding, four types of microfluidic chips were made with GPPS (general purpose polystyrene), and a 100㎛-thick PDMS (polydimethylsiloxane) film was attached to the top of each microfluidic chip. As a result of observing the flow of the culture medium in the microchannel, it was confirmed that when the aspect ratio (height/width) of the microchannel is 1.5 or more, the fluid flows from the inlet to the outlet without a backflow phenomenon. In addition, the culture efficiency experiments of colorectal cancer cells (SW490) were performed in a 3D culture system in which PDMS films with different pore diameters (1/25/45 ㎛) were combined on a microfluidic chip. As a result, it was found that the cell growth rate increased up to 1.3 times and the cell death rate decreased by 71% as a result of the 3D culture system having a hole membrane with a diameter of 10 ㎛ or more compared to the conventional commercial. Based on the results of this study, it is possible to expand and build various 3D cell culture systems that can maximize cell culture efficiency by cell type by adjusting the shape of the microchannel, the size of the film hole, and the flow rate of the inlet.

• Transactions of the Korean Society of Mechanical Engineers A
• /
• v.30 no.10 s.253
• /
• pp.1261-1268
• /
• 2006

This paper reports low-cost microreactor $(10{\mu}{\ell})$ biochip for the DNA PCR (polymerase chain reaction). The microbiochip $(20mm{\times}28mm)$ is a hybrid type which is composed of PDMS (polydimethylsiloxane) layer with serpentine micochannel $(360{\mu}m{\times}100{\mu}m)$ chamber and glass substrate integrated with microheater and thermal microsensor. Undesirable bubble is usually created during sample loading to PMDS-based microchip because of hydrophobic chip surface. Created bubbles interrupt stable biochemical reaction. We designed improved microreactor chamber using microfluidic simulation. The designed reactor has a coner-rounded serpentine channel architecture, which enables stable injection into hydrophobic surface using micropipette only. Reactor temperature needed to PCR reaction is controlled within ${\pm}0.5^{\circ}C$ by PID controller of LabVIEW software. It is experimentally confirmed that SRY gene PCR by the fabricated microreactor chip is performed for less than 54 min.

• Proceedings of the Korean Magnestics Society Conference
• /
• 2007.05a
• /
• pp.91.2-91.2
• /
• 2007

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.157-158
• /
• 2005