Excelsior: A High Throughput Particle Spectroscopic Characterization System for Biologic QA/QC

Period of Performance: 09/10/2015 - 02/29/2016


Phase 1 SBIR

Recipient Firm

Optofluidics, Inc.
3711 Market Street, Suite 970 Array
Philadelphia, PA 19104
Principal Investigator


DESCRIPTION (provided by applicant): Optofluidics Inc. proposes to develop the "Excelsior" - a high-throughput nanoparticle enumeration and speciation (ID) instrument for QA/QC in protein therapeutics. The need for enhanced sub visible particle compositional characterization in the 0.1 to 10µm range is a stated need of the FDA Chemical, Manufacturing and Controls Guidance Division. This is best illustrated in the draft Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products released in February 2013 which states "sub visible particulates in the size range of 0.1-10 microns have a strong potential to be immunogenic, but are not precisely monitored by currently employed technologies". The reason for this need is that "there is a wealth of data from animal studies and correlative human data that indicate that the presence of ... sub visible particles enhances the immunogenicity of ... protein therapeutics" (FDA Office of Biotechnology Products Director Dr. Amy Rosenberg et al, J. Pharmaceutical Sciences, 2012). Our "Excelsior" Raman ID system works by observing the non-linearly scattered (Raman) light from particles captured in the near-field of an optical waveguide. As we demonstrate in the proposal, this ability to confine particles in the high intensity region of the near-field enables us to collect strong Raman spectra from them while maintaining short enough exposure times to enable throughputs consistent with industrial requirements. We have built a prototype instrument system and demonstrated the feasibility of the near-field Raman ID technique using an assortment of sub-micron particles. Given this, our goals in Phase I are to demonstrate the ability to rapidly ID and enumerate particle/protein aggregate mixtures and to obtain validation data using a sample provided by our industrial collaborators.