title: Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS): A Novel Process Flow for Quality Control Screening of Compound Libraries.
abstract: In the early stages of drug discovery, high-throughput screening (HTS) of compound libraries against pharmaceutical targets is a common method to identify potential lead molecules. For these HTS campaigns to be efficient and successful, continuous quality control of the compound collection is necessary and crucial. However, the large number of compound samples and the limited sample amount pose unique challenges. Presented here is a proof-of-concept study for a novel process flow for the quality control screening of small-molecule compound libraries that consumes only minimal amounts of samples and affords compound-specific molecular data. This process employs an acoustic sample deposition (ASD) technique for the offline sample preparation by depositing nanoliter volumes in an array format onto microscope glass slides followed by matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analysis. An initial study of a 384-compound array employing the ASD-MALDI-MS workflow resulted in a 75% first-pass positive identification rate with an analysis time of <1 s per sample.
authors.affiliation: Bristol-Myers Squibb Company, Research & Development, Disease Sciences and Biologics, Leads Discovery and Optimization, Wallingford, CT, USA.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Chin
authors.affiliation: Bristol-Myers Squibb Company, Research & Development, Disease Sciences and Biologics, Leads Discovery and Optimization, Wallingford, CT, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wood
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
authors.forename: Grace S
authors.initials: GS
authors.lastname: Peters
authors.affiliation: Bristol-Myers Squibb Company, Research & Development, Pharmaceutical Candidate Optimization, Bioanalytical and Discovery Analytical Sciences, Wallingford, CT, USA dieter.drexler@bms.com.
authors.forename: Dieter M
authors.initials: DM
authors.lastname: Drexler
mesh_terms: D000162:Acoustics; D020811:Biomedical Technology / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D011786:Quality Control; D054852:Small Molecule Libraries; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D054852:Small Molecule Libraries; D012996:Solutions
keywords: MALDI-MS; acoustic sample deposition; high-throughput screening