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

Abstract：

: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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Iannotti MJ,MacArthur R,Jones R,Tao D,Singeç I,Michael S,Inglese J

doi

10.1021/acschembio.9b00001

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

497-505

issue

3

eissn

1554-8929

issn

1554-8937

journal_volume

14

pub_type

杂志文章

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