Send to

Choose Destination
ACS Chem Biol. 2019 Mar 15;14(3):497-505. doi: 10.1021/acschembio.9b00001. Epub 2019 Feb 14.

Detecting Secretory Proteins by Acoustic Droplet Ejection in Multiplexed High-Throughput Applications.

Author information

National Center for Advancing Translational Sciences , National Institutes of Health , Rockville , Maryland 20850 , United States.


Nearly one-third of the encoded proteome is comprised of secretory proteins that enable communication between cells and organ systems, playing a ubiquitous role in human health and disease. High-throughput detection of secreted proteins would enhance efforts to identify therapies for secretion-related diseases. Using the Z mutant of alpha-1 antitrypsin as a human secretory model, we have developed 1536-well high-throughput screening assays that utilize acoustic droplet ejection to transfer nanoliter volumes of sample for protein quantification. Among them, the acoustic reverse phase protein array (acoustic RPPA) is a multiplexable, low-cost immunodetection technology for native, endogenously secreted proteins from physiologically relevant model systems like stem cells that is compatible with plate-based instrumentation. Parallel assay profiling with the LOPAC1280 chemical library validated performance and orthogonality between a secreted bioluminescent reporter and acoustic RPPA method by consistently identifying secretory modulators with comparable concentration response relationships. Here, we introduce a robust, multiplexed drug discovery platform coupling extracellular protein quantification by acoustic RPPA with intracellular and cytotoxicity analyses from single wells, demonstrating proof-of-principle applications for human induced pluripotent stem cell-derived hepatocytes.


Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center