Demonstration of a compact deep UV Raman spatial heterodyne spectrometer for biologics analysis

Abstract

Monoclonal antibodies and antibody fragments are increasingly important classes of biotherapeutics. However, these products are both challenging and expensive to manufacture. New process analytical technologies used to monitor these products during their manufacture are of significant interest. Deep UV Raman spectroscopy promises to provide the required specificity and accuracy, however instruments, have historically been large and complex. In this paper, a new deep UV Raman instrument is described using a solid-state laser and a spatial heterodyne spectrometer. The instrument overcomes practical limitations of the technique and could readily be used for online measurement. A series of observations have been made of biopharmaceutical products, including immunoglobulin G and domain antibodies. Where high levels of both specificity and linearity when measuring samples of different concentration with a precision of better than 0.05 mg/mL has been demonstrated.

Continuous-wave second-harmonic generation in the far-UVC pumped by a blue laser diode

“…A relatively compact demonstration with an external-cavity diode laser (ECDL) pump at 445 nm achieved far-UVC using bulk BBO, though with low conversion efficiency ( ∼0.01 % for 1.4 W pump) 33 . Recent advancements using resonant cavities showed improved efficiency with 13 % conversion from a 200 mW pump and 34 % conversion using cascaded SHG from a 1.6 W pump, both producing signals at ∼229 nm 34,35 . However, these systems require complex bulk optics for implementation.…”