Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform
Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in anti...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523004501 |
| _version_ | 1797248344869830656 |
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| author | Fangchi Shao Hui Li Kuangwen Hsieh Pengfei Zhang Sixuan Li Tza-Huei Wang |
| author_facet | Fangchi Shao Hui Li Kuangwen Hsieh Pengfei Zhang Sixuan Li Tza-Huei Wang |
| author_sort | Fangchi Shao |
| collection | DOAJ |
| description | Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR. |
| first_indexed | 2024-04-24T20:13:06Z |
| format | Article |
| id | doaj.art-6329bace034a43b98ea4ae5ea9ca19c8 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-24T20:13:06Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6329bace034a43b98ea4ae5ea9ca19c82024-03-23T06:24:03ZengElsevierActa Pharmaceutica Sinica B2211-38352024-04-0114418011813Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platformFangchi Shao0Hui Li1Kuangwen Hsieh2Pengfei Zhang3Sixuan Li4Tza-Huei Wang5Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Corresponding author.Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.http://www.sciencedirect.com/science/article/pii/S2211383523004501Droplet microfluidicsAntimicrobial resistanceAntibiotic combinatorial screeningContact printingRoboticsPharmaceutical analysis |
| spellingShingle | Fangchi Shao Hui Li Kuangwen Hsieh Pengfei Zhang Sixuan Li Tza-Huei Wang Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform Acta Pharmaceutica Sinica B Droplet microfluidics Antimicrobial resistance Antibiotic combinatorial screening Contact printing Robotics Pharmaceutical analysis |
| title | Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform |
| title_full | Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform |
| title_fullStr | Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform |
| title_full_unstemmed | Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform |
| title_short | Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform |
| title_sort | automated and miniaturized screening of antibiotic combinations via robotic printed combinatorial droplet platform |
| topic | Droplet microfluidics Antimicrobial resistance Antibiotic combinatorial screening Contact printing Robotics Pharmaceutical analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523004501 |
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