High throughput screening of particle conditioning operations: I. System design and method development

2015 ◽  
Vol 112 (8) ◽  
pp. 1554-1567 ◽  
Author(s):  
Aaron Noyes ◽  
Ben Huffman ◽  
Ranga Godavarti ◽  
Nigel Titchener-Hooker ◽  
Jonathan Coffman ◽  
...  
2021 ◽  
pp. 247255522110281
Author(s):  
Roman P. Simon ◽  
Tim T. Häbe ◽  
Robert Ries ◽  
Martin Winter ◽  
Yuting Wang ◽  
...  

Acoustic droplet ejection (ADE)–open port interface (OPI)–mass spectrometry (MS) has recently been introduced as a versatile analytical method that combines fast and contactless acoustic sampling with sensitive and accurate electrospray ionization (ESI)–MS-based analyte detection. The potential of the technology to provide label-free measurements in subsecond analytical cycle times makes it an attractive option for high-throughput screening (HTS). Here, we report the first implementation of ADE-OPI-MS in a fully automated HTS environment, based on the example of a biochemical assay aiming at the identification of small-molecule inhibitors of the cyclic guanosine monophosphate–adenosine monophosphate (GMP-AMP) synthase (cGAS). First, we describe the optimization of the method to enable sensitive and accurate determination of enzyme activity and inhibition in miniaturized 1536-well microtiter plate format. Then we show both results from a validation single-concentration screen using a test set of 5500 compounds, and the subsequent concentration–response testing of selected hits in direct comparison with a previously established matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) readout. Finally, we present the development of an in-line OPI cleaning procedure aiming to match the instrument robustness required for large-scale HTS campaigns. Overall, this work points to critical method development parameters and provides guidance for the establishment of integrated ADE-OPI-MS as HTS-compatible technology for early drug discovery.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
L Hingorani ◽  
NP Seeram ◽  
B Ebersole

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
K Georgousaki ◽  
N DePedro ◽  
AM Chinchilla ◽  
N Aliagiannis ◽  
F Vicente ◽  
...  

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
LS Espindola ◽  
RG Dusi ◽  
KR Gustafson ◽  
J McMahon ◽  
JA Beutler

2014 ◽  
Author(s):  
Clair Cochrane ◽  
Halil Ruso ◽  
Anthony Hope ◽  
Rosemary G Clarke ◽  
Christopher Barratt ◽  
...  

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