An Image-Based High-Throughput and High-Content Drug Screening Method Based on Microarray and Expansion Microscopy

Area of Science:

• Biotechnology
• Drug Discovery
• Microscopy

Background:

• High-efficiency drug screening is crucial due to numerous targets and lengthy assessment times.
• Combining high throughput and high content in image-based drug screening remains a significant challenge.

Purpose of the Study:

• To develop a high-throughput and high-content drug screening method.
• To overcome limitations in current image-based drug screening techniques.

Main Methods:

• Fabrication of a superhydrophobic microwell array plate (SMAP) using photolithography.
• Cell culture and drug treatment within the SMAP using microcolumn-microwell sandwiching technology.
• Super-resolution imaging via protein-retention expansion microscopy (proExM) after drug treatment.

Main Results:

• Demonstrated successful collection of a 7x7 image array of microtubules within 3 hours at 68 nm resolution.
• Qualitative and quantitative analyses revealed detailed morphological changes in microtubules and mitochondria.
• Confirmed the effective combination of high throughput and high content in the developed method.

Conclusions:

• The developed SMAP and proExM method offers a significant advancement in drug screening efficiency.
• This integrated approach enables more detailed analysis of cellular responses to drug treatment.
• The method holds promise for accelerating the identification of potential drug candidates.