title: Novel Acoustic Loading of a Mass Spectrometer: Toward Next-Generation High-Throughput MS Screening.
abstract: High-throughput, direct measurement of substrate-to-product conversion by label-free detection, without the need for engineered substrates or secondary assays, could be considered the "holy grail" of drug discovery screening. Mass spectrometry (MS) has the potential to be part of this ultimate screening solution, but is constrained by the limitations of existing MS sample introduction modes that cannot meet the throughput requirements of high-throughput screening (HTS). Here we report data from a prototype system (Echo-MS) that uses acoustic droplet ejection (ADE) to transfer femtoliter-scale droplets in a rapid, precise, and accurate fashion directly into the MS. The acoustic source can load samples into the MS from a microtiter plate at a rate of up to three samples per second. The resulting MS signal displays a very sharp attack profile and ions are detected within 50 ms of activation of the acoustic transducer. Additionally, we show that the system is capable of generating multiply charged ion species from simple peptides and large proteins. The combination of high speed and low sample volume has significant potential within not only drug discovery, but also other areas of the industry.
authors.affiliation: SSCM AstraZeneca Alderley Park, Macclesfield, UK Ian.Sinclair@astrazeneca.com.
authors.forename: Ian
authors.initials: I
authors.lastname: Sinclair
authors.affiliation: Labcyte, Inc., Sunnyvale, CA, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Stearns
authors.affiliation: R&D Waters Corporation, Wilmslow, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Pringle
authors.affiliation: SSCM AstraZeneca Alderley Park, Macclesfield, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wingfield
authors.affiliation: Labcyte, Inc., Sunnyvale, CA, USA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Datwani
authors.affiliation: Labcyte, Inc., Sunnyvale, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hall
authors.affiliation: Labcyte, Inc., Sunnyvale, CA, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Ghislain
authors.affiliation: Labcyte, Inc., Sunnyvale, CA, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Majlof
authors.affiliation: SSCM AstraZeneca Alderley Park, Macclesfield, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bachman
mesh_terms: D000162:Acoustics; D057205:Automation, Laboratory / Q000295:instrumentation / Q000379:methods*; D020811:Biomedical Technology / Q000295:instrumentation / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D012996:Solutions; D013997:Time Factors
chemical_list: D012996:Solutions
keywords: acoustic droplet ejection; high-throughput screening (HTS); mass spectrometry; robotics and instrumentation