SLAS Technology (Dec 2022)
Integrated and automated high-throughput purification of libraries on microscale
- Carol Ginsburg-Moraff,
- Jonathan Grob,
- Karl Chin,
- Grant Eastman,
- Sandra Wildhaber,
- Mark Bayliss,
- Heinrich M. Mues,
- Marco Palmieri,
- Jennifer Poirier,
- Marcel Reck,
- Alexandre Luneau,
- Stephane Rodde,
- John Reilly,
- Trixie Wagner,
- Cara E. Brocklehurst,
- René Wyler,
- David Dunstan,
- Alexander N. Marziale, PhD
Affiliations
- Carol Ginsburg-Moraff
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA; Corresponding authors.
- Jonathan Grob
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA
- Karl Chin
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA
- Grant Eastman
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA
- Sandra Wildhaber
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Mark Bayliss
- Virscidian Inc., Cary, NC 27511, USA
- Heinrich M. Mues
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Marco Palmieri
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Jennifer Poirier
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA
- Marcel Reck
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Alexandre Luneau
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Stephane Rodde
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- John Reilly
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Trixie Wagner
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- Cara E. Brocklehurst
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- René Wyler
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland
- David Dunstan
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Cambridge, MA 02139, USA; Corresponding authors.
- Alexander N. Marziale, PhD
- Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG., Fabrikstrasse 1, Basel 4056, Switzerland; Corresponding authors.
- Journal volume & issue
-
Vol. 27,
no. 6
pp. 350 – 360
Abstract
We herein report the development of an automation platform for rapid purification and quantification of chemical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on analytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.