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LAB ON A CHIP · 2023 ·Vol. 23 ·期 18 ·3961-3977 · IF 6.1

Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system

Deyu Yang,Ziming Yu,Mengxin Zheng,Wei Yang,Zhangcai Liu,Jianhua Zhou,Lu Huang

Microfluidic platforms have been employed as an effective tool for drug screening and exhibit the advantages of lower reagent consumption, higher throughput and a higher degree of automation. Despite the great advancement, it remains challenging to screen complex antibiotic combinations in a simple, high-throughput and systematic manner. Meanwhile, the large amounts of datasets generated during the screening process generally outpace the abilities of the conventional manual or semi-automatic data analysis. To address these issues, we propose an artificial intelligence-accelerated high-throughput combinatorial drug evaluation system (AI-HTCDES), which not only allows high-throughput production of antibiotic combinations with varying concentrations, but can also automatically analyze the dynamic growth of bacteria under the action of different antibiotic combinations. Based on this system, several antibiotic combinations displaying an additive effect are discovered, and the dosage regimens of each component in the combinations are determined. This strategy not only provides useful guidance in the clinical use of antibiotic combination therapy and personalized medicine, but also offers a promising tool for the combinatorial screenings of other medicines.

研究领域: 药学 · 微流控技术 · 人工智能 · 生物医学工程
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Small Methods · 2023 · IF 12.4

A Nano-Electroporation-DNA Tensioner Platform Enhances Intracellular Delivery and Mechanical Analysis Toward Rapid Drug Assessment

Xinxin Hang,Zhaocun Huang,Shiqi He,Zhiying Wang,Zaizai Dong,Lingqian Chang

In vitro, drug assessment holds tremendous potential to success in novel drug development and precision medicine. Traditional techniques for drug assessment, however, face remarkable challenges to achieve high speed, as limited by incubation-based drug delivery (>several hours) and cell viability measurements (>1 d), which significantly compromise the efficacy in clinical trials. In this work, a nano-electroporation-DNA tensioner platform is reported that shortens the time of drug delivery to less than 3 s, and that of cellular mechanical force analysis to 30 min. The platform adopts a nanochannel structure to localize a safe electric field for cell perforation, while enhancing delivery speed by 10 3 times for intracellular delivery, as compared to molecular diffusion in coculture methods. The platform is further equipped with a DNA tensioner to detect cellular mechanical force for quantifying cell viability after drug treatment. Systematic head-to-head comparison, by analyzing FDA (food and drug administration)-approved drugs (paclitaxel, doxorubicin), demonstrated the platform with high speed, efficiency, and safety, showing a simple yet powerful tool for clinical drug screening and development.

研究领域: 生物技术 · 药学 · 细胞生物学 · 药物开发 · 精准医学
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