Bordo Mark W, Oketokoun Rafiou, Cross Conor J, Bao Kai, Lee Jeong Heon, Feygin Ilya, Chang Alex B, Frangioni John V, Choi Hak Soo
†Curadel, LLC, 377 Plantation Street, Worcester, Massachusetts 01605, United States.
‡Robotic Chemistry Group, Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
ACS Comb Sci. 2015 May 11;17(5):303-9. doi: 10.1021/acscombsci.5b00013. Epub 2015 Apr 22.
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.
单珠单化合物（OBOC）固相组合化学已在药物研发中得到广泛应用。然而，一个主要瓶颈是将仍在有机溶剂中溶胀的单个珠子分选到微孔板的各个孔中。为了解决这个问题，我们构建了一个具有集成质量控制的自动化珠子分选系统，该系统能够将大量珠子批量分选并放置到384孔板的单个孔中，整个过程都在有机溶剂中进行。该珠子分选仪采用独特的往复式流体设计，每1.5秒能够沉积1个珠子，平均准确率为97%。我们通过分选8500多个珠子，然后裂解共轭化合物并通过液相色谱/质谱（LC/MS）确认每个珠子的化学身份，对该仪器的性能进行了量化。该仪器应能够更高效地筛选组合小分子文库，而无需干燥珠子或以其他方式改变化学环境。
