title: High-Throughput Sorting and Placement of One-Bead-One-Compound (OBOC) Libraries from Bulk to Single Wells in Organic Solvent.
abstract: One-bead-one-compound (OBOC) solid-phase combinatorial chemistry has been used extensively in drug discovery. However, a major bottleneck has been the sorting of individual beads, while still swollen in organic solvent, into individual wells of a microwell plate. To solve this problem, we have constructed an automated bead sorting system with integrated quality control that is capable of sorting and placing large numbers of beads in bulk to single wells of a 384-well plate, all in an organic solvent. The bead sorter employs a unique, reciprocating fluidic design capable of depositing 1 bead every 1.5 s, with an average accuracy of 97%. We quantified the performance of this instrument by sorting over 8500 beads, followed by cleaving the conjugated compound and confirming the chemical identity of each by liquid chromatography/mass spectrometry (LC/MS). This instrument should enable more efficient screening of combinatorial small molecule libraries without the need to dry beads or otherwise change the chemical environment.
authors: †Curadel, LLC, 377 Plantation Street, Worcester, Massachusetts 01605, United States.
authors: Mark W
authors: MW
authors: Bordo
authors: ‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Rafiou
authors: R
authors: Oketokoun
authors: ‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Conor J
authors: CJ
authors: Cross
authors: ‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Kai
authors: K
authors: Bao
authors: ‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Jeong Heon
authors: JH
authors: Lee
authors: ⊥TechElan LLC, 853 Hillside Ave., Mountainside, New Jersey 07092, United States.
authors: Ilya
authors: I
authors: Feygin
authors: ⊥TechElan LLC, 853 Hillside Ave., Mountainside, New Jersey 07092, United States.
authors: Alex B
authors: AB
authors: Chang
authors: †Curadel, LLC, 377 Plantation Street, Worcester, Massachusetts 01605, United States.
authors: John V
authors: JV
authors: Frangioni
authors: ‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Hak Soo
authors: HS
authors: Choi
mesh_terms: D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D057166:High-Throughput Screening Assays; D013058:Mass Spectrometry; D009930:Organic Chemicals / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D012984:Software; D012997:Solvents / Q000737:chemistry*
chemical_list: D009930:Organic Chemicals; D054852:Small Molecule Libraries; D012997:Solvents
keywords: OBOC; bead sorting; combinatorial libraries; high-throughput screening; organic solvents