Luke Arbogast

Brinson Group

Contact

Email: larboga1@umd.edu

Call: (240) 314-6270

Education

2006, B.S. Chemistry, Virginia Commonwealth University

2013, Ph.D. Chemistry, Johns Hopkins University 

Profile

Dr. Luke Arbogast  is a NIST research chemist working on the development, validation and application of nuclear magnetic resonance (NMR) methods to address critical needs in biopharmaceutical characterization.  Current areas of interest include development of solid-state NMR methods fo structural characterization of lyophilized protein therapeutics as well investigation of NMR-based metabolomics measurements for use as a bioprocess analytical technology.

Current Research

Comparative Analysis of 1D and 2D NMR Methods for Biopharmaceutical Characterization

1D and 2D NMR spectra of an IgG1 mAb

In the past decade, NMR has grown from an emerging method with promise to improve the structural characterization of protein therapeutics to mature method seeing increased adoption by the industry. In that time a number of different NMR approaches have been proposed and developed for such characterization, including 1D 1H-based methods, as well as 2D 1H-13C methyl correlated methods.  Both approaches have relative performance attributes related to their inherent resolution and sensitivity. 1D proton based methods offer high sensitivity and cover the complete chemical environments of the protein, but accordingly suffer from poor resolution, whereas 2D methyl based methods offer high spectral and structural resolution, but report on only a subset of protein environments and are of low sensitivity at natural isotopic abundance. Given the complementarity of the attributes of the two approaches, the development of NMR as an an integrated multi-modal approach for characterization of biotherapeutics would be of great benefit to the industry. To that end, we have conducted studies to directly compare the performance of 1D-proton and 2D-methyl approaches to report on structural variation across a set of monoclonal antibody (mAb) samples. Results of our efforts demonstrate the robustness and reproducibility of both methods as well as their differing sensitivity to chemical structure and molecular size.  These results illustrate how employing NMR as a multi-modal platform provides a more complete pictures of structure in the biopharmaceutical context.  More recently, we have extended this methodology by application of NIPALS based PCA to both the 1D and 2D modalities to maximize utilization of structural information and to provide quantitative assessment of spectral similarity; we dub this new approach PROtein Fingerprints Obtained Using NIPALS Decomposition (PROFOUND). 

 

 

Postdoctoral Positions Available in NMR in Biomanufacturing: