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      • A lung cancer-on-chip platform with integrated biosensors for physiological monitoring and toxicity assessment

        Khalid, Muhammad Asad Ullah,Kim, Young Soo,Ali, Muhsin,Lee, Byung Gul,Cho, Young-Jae,Choi, Kyung Hyun Elsevier 2020 Biochemical engineering journal Vol.155 No.-

        <P><B>Abstract</B></P> <P>Numerous micro-physiological systems have been reported to successfully mimic the organ microenvironment. However, there are currently only a few systems that focus on real-time physiological monitoring for preclinical cytotoxicity assessment of drug candidates. We developed a multi-sensor lung cancer-on-chip platform for trans-epithelial electrical (TEER) impedance based cytotoxicity evaluation of drug candidates. The excellent transparency of ITO electrodes allowed for visual monitoring of cells on chip using a 3D-printed digital microscope, which has not been previously reported. An optical pH sensor was used for online monitoring of media pH. As a proof of concept, lung cancer NCI-H1437 cells were cultured on glass-based microfluidic chip and biosensors data were obtained in real-time. The toxicity of different concentrations of drugs doxorubicin (DOX) and docetaxel was then monitored in real-time using the TEER impedance sensor. The TEER impedance response was evaluated in terms of cell index (CI), whereas a live/dead assay was performed for the comparison of cell viability at the end of the experiments. The cell index assessment suggested that the increasing concentrations of doxorubicin resulted in a higher cell death rate than docetaxel. The pH response and microscopic images were also recorded during drug treatment. The platform we developed here, is a promising tool for the cytotoxicity evaluation of novel drug compounds for future micro-physiological systems and development of personalized medicine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A lung cancer-on-chip platform was developed for real-time physiological monitoring. </LI> <LI> All the biosensors were developed in-house including pH, and TEER impedance sensors. </LI> <LI> Transparent ITO electrode allowed for visual monitoring using 3D-printed microscope. </LI> <LI> The toxicity of anticancer drugs doxorubicin and docetaxel was evaluated. </LI> <LI> A comparison of impedimetric and live/dead cell viabilities was also analyzed. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

        FAROOQI HAFIZ MUHAMMAD UMER,Kang Bohye,Khalid Muhammad Asad Ullah,Salih Abdul Rahim Chethikkattuveli,Hyun Kinam,박성혁,Huh Dongeun,최경현 나노기술연구협의회 2021 Nano Convergence Vol.8 No.3

        Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

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        Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening

        Arun Asif,박성혁,Afaque Manzoor Soomro,Muhammad Asad Ullah Khalid,Abdul Rahim Chattikatikatuveli Salih,강보혜,Faheem Ahmed,김경환,최경현 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.98 No.-

        In microfluidics, the emergingfield of microphysiological systems (MPS) is overcoming the challenge ofphysiological irrelevancy by animal models for drug discovery and development. Liver function iscritically influenced by drugs owing to its role in drug metabolism and detoxification. Human serumalbumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. Amicrofluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS forcontinuous feedback over disease modeling and treatment. A gold-electrode based electrochemicalimmunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to beefficient for live monitoring of disease modelling and drug treatment over the period of 6 days. Thesystem emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit ofintegrated sensor was 1 mg/ml with successive reproducibility. The proposed sensor was also validatedwith metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liverinjury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform tomimic real-time drug assessment.

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