Droplet Microarray as a Powerful Platform for Seeking New Antibiotics Against Multidrug‐Resistant Bacteria

Abstract

Multidrug‐resistant (MDR) bacteria is a severe threat to public health. Therefore, it is urgent to establish effective screening systems for identifying novel antibacterial compounds. In this study, a highly miniaturized droplet microarray (DMA) based high‐throughput screening system is established to screen over 2000 compounds for their antimicrobial properties against carbapenem‐resistant Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus (MRSA). The DMA consists of an array of hydrophilic spots divided by superhydrophobic borders. Due to the differences in the surface wettability between the spots and the borders, arrays of hundreds of nanoliter‐sized droplets containing bacteria and different drugs can be generated for screening applications. A simple colorimetric viability readout utilizing a conventional photo scanner is developed for fast single‐step detection of the inhibitory effect of the compounds on bacterial growth on the whole array. Six hit compounds, including coumarins and structurally simplified estrogen analogs are identified in the primary screening and validated with minimum inhibition concentration assay for their antibacterial effect. This study demonstrates that the DMA‐based high‐throughput screening system enables the identification of potential antibiotics from novel synthetic compound libraries, offering opportunities for development of new treatments against multidrug‐resistant bacteria.

Supporting Sustainability of Chemistry by Linking Research Data with Physically Preserved Research Materials

“…The provision of samples to the Molecule Archive has been the origin of many publications that were done in collaboration with compound providers and re-usersapproving that the provision of data can result directly in more visibility and impact for the scientists sharing their research results. 32,33,34,35,36,37,38 https://doi.org/10.26434/chemrxiv-2023-2dd4c ORCID: https://orcid.org/0000-0001-9513-2468 Content not peer-reviewed by ChemRxiv. License: CC BY 4.0 generation of, e.g., molecular descriptors facilitate the work of the scientists as the most suitable descriptors for a search for chemical compounds are generated by the software without additional efforts.…”

Fundamentals and Applications of Surface Wetting

“…For instance, as reviewed above, the flow patterns during the evaporation of a droplet can be used for biological and chemical assays. These platforms are much faster than traditional microwells and have a huge potential to scale up by using arrays of sessile droplets. , Further research on intracellular drug delivery , platforms is essential for faster drug screening. Artificial intelligence and machine learning are rapidly changing the scope and area of sensing, surface fabrication, and characterizations.…”

High‐Throughput Synthesis and Machine Learning Assisted Design of Photodegradable Hydrogels

“…[41] It has proven as a potent platform for miniaturized chemistry and biology. [42,43] Combinatorial library synthesis through a polymer-based solid-phase synthesis strategy to achieve a synthesis of various structural motives has been realized and demonstrated for on-chip synthesis and screening. [44,45] Our experimental synthesis workflow is based on the preparation of sub-microliter-sized hydrogels in the hydrophilic spots of DMA.…”