• Journal of Sensor Science and Technology
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• v.29 no.2
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• pp.100-104
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• 2020

Thus far, several in vivo biosensing platforms have been proposed to measure the mechanical contractility of cultured cardiomyocytes. However, the low sensitivity and screening rate of the developed sensors severely limit their practical applications. In addition, intensive research and development in cardiovascular disease demand a high-throughput drug-screening platform based on biomimetic engineering. To overcome the drawbacks of the current state-of-the-art methods, we propose a high-throughput drug-screening platform based on 16 functional high-sensitivity well plates. The proposed system simulates the physiological accuracy of the heart function in an in vitro environment. We fabricated 64 cantilevers using highly flexible and optically transparent silicone rubber and placed in 16 independent wells. Nanogrooves were imprinted on the surface of the cantilever to promote cell alignment and maturation. The adverse effects of the cardiovascular drugs on the cultured cardiomyocytes were systematically investigated. The 64 cantilevers demonstrated a highly reliable and reproducible mechanical contractility of the drug-treated cardiomyocytes. Real-time high-throughput screening and simultaneous evaluation of the cardiomyocyte mechanical contractility under multiple drugs verified that the proposed system could be used as an efficient drugtoxicity test platform.

• Bulletin of the Korean Chemical Society
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• v.32 no.9
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• pp.3229-3232
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• 2011

A FRET-based high-throughput screening system was developed for the discovery of competitive smallmolecule Hsp90 inhibitors. The biarsenical fluorescein derivative FlAsH and dabcyl-conjugated Hsp90 inhibitor GM were employed as the FRET donor and quencher, respectively. The spatial proximity perturbation between FlAsH-labeled Hsp90N and GM-dabcyl upon treatment of a small molecule led to changes in the FRET-induced fluorescence, monitored in a high-throughput fashion.

• Archives of Pharmacal Research
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• v.23 no.3
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• pp.246-251
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• 2000

In most tissues, apoptosis plays a pivotal role in normal development and for regulating cell number, thus inappropriate apoptosis underlies a variety of diseases. Caspase-3 is one of a family of caspases that are mainly involved in the apoptotic signal transduction pathway, where caspase-3 acts as an effect molecule to proteolytically cleave intracellular substrates that are necessary for maintaining cell survival. Recent evidences show that apoptotic cell death can be blocked by inhibiting caspase-3, suggesting its inhibitors have potential to be therapeutic drugs for the diseases related with inappropriate apoptosis. We have established a screening system to search caspase-3 inhibitors from chemical libraries stocked in our institute. The enzyme assay is configured entirely in 96-well format, which is easily adapted for high throughput screening. Before performing mass screening, 80 in-house compounds were screened as a preliminary experiment, and we found that morin hydrate inhibited caspase-3 by 66.4 % at the final concentration of 20 ${\mu}g/m{\ell}$.

• The Korean Journal of Pesticide Science
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• v.5 no.3
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• pp.41-46
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• 2001

This study was conducted to develop a high throughput system for screening acetolactate synthase(ALS) inhibitors, and to detect basic mother molecules for developing new novel herbicide candidates. The high throughput screening (HTS) method using 96-well plate and microplate reader was developed. This method is 8 times more effective than basic technique in one cycle per person. Futhermore, considering for less than 1/10 volume of materials required for ALS test and enzyme kinetics with 16 times faster speed compared to those of former procedure, this HTS method has more than 100 times higher efficacy than basic system in a consecutive procedure. We discovered 11 new ALS inhibitors such as 2-oxoglutaric acid, aminooxyacetic acid, azelaic acid, citric acid, cyanuric fluoride, itaconic acid, malonic acid, niclosamide, oxalic acid, glyoxylic acid, and suramin from 107 commercial plant-specific inhibitors using this technique. We hope these results might be useful to discover lead compounds for developing new novel herbicide candidate.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.88-89
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• 2002

Traditionally, kinetics of brain influx of drugs has been evaluated by a number of experimental techniques. Brain uptake index and in situ brain perfusion study have been used for the determination of the kinetics; However, these methods generally focus on the accuracy of the uptake rate into the brain rather than the speed of the determination. In addition, application of radiolabelled substrates (e.g., $_{14}$C-labelled sucrose) further impedes the wide spread acceptance of these techniques for the application of high throughput screening system. (omitted)

• Korean Chemical Engineering Research
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• v.52 no.2
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• pp.141-153
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• 2014

Droplet based microfluidic systems have been developed for the application of biological and chemical research field. A picoliter droplet in microfluidic device provides a compartmentalized and well-defined reactor in miniaturized system. The microfluidic system with small droplets can reduce reagent cost and enhance efficiency through automated high-throughput screening system. In this review, we summarize the functionality of droplet based microfluidic system including droplet generation, precise droplet control, and various applications. In addition, this article reviews current applications in chemistry and biology, and discuss advantages of droplet based microfluidics compared with conventional manner.

• Journal of Life Science
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• v.18 no.9
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• pp.1312-1315
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• 2008

High throughput-drug screening plays a pivotal role for early stage of drug discovery process. In the course of assay development for screening of cell death-inducing agents, a protocol that is simple, time-saving, and high throughput-compatible was designed which was confirmed that the protocol can be worked by a HTS-compatible machine. In 96-well format, PC-3 cancer cells (1${\times}10^{4}$ cells/ml) were cultured for 24 hr. After 24 h-incubation with various medicinal plants extracts, the cells were then stained with DAPI for 30 min. The fluorescence intensity of the stained cells was measured semi-automatically with a multilabel counter. To test whether the present assay system effectively works, we screened about 850 medicinal plant extracts, and selected 1 positive crude extracts that contained cell death-inducing activity. These results suggest that the protocol is highly amenable to HTS implementation for a cell death-inducing agent(s).

• Food Science and Preservation
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• v.12 no.3
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• pp.267-274
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• 2005

Oxidant stress is a well-known pivotal parameter for the degenerative immune diseases including asthma, atopic dermatitis, and rhinitis. In order to screen for anti-asthma agents effectively, we first established the infrastructure of high throughput screening(HTS) for anti-oxidant agents from agricultural products and/or oriental medicine library extracted with water, methanol, dimethyl sulfoxide, ethyl acetate and juice, Using the screening system, we found that Chaenomelis langenariae, Rhus javanica L., Camellia sinensis, Helianthus annuus and Angelica utilis Makino had strong anti-oxidant activity. Moreover, Helianthus annuus, Rehmannia glutinosa Libo and Angelica utilis Makino have protection activities by treatment of an oxidant hydrogen peroxide. Together, these results suggest that screened agents could be potential agents against asthma, although the in vivo studies should be clearly tested.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.355-362
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• 2014

We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.213-225
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• 2016

To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as high-content screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner.