Continuous Fiber-Optic Probe for Detection of Antibodies and Fc Fusions

This project advances a continuous fiber‑optic process analytical technology (PAT) probe that uses immobilized fluorescent Fc‑binding ligands to provide fast, real‑time measurement of antibody and Fc‑fusion concentrations in flowing bioprocess streams.

Industry Need

Biopharmaceutical manufacturers urgently need rapid, molecule‑specific, real‑time measurements of antibody concentration to support Protein A load‑phase control, early breakthrough detection, UF/DF leak identification, and continuous or intensified downstream processing. Current approaches—offline HPLC or ELISA assays, UV280 sensors that suffer from matrix interference, and spectroscopic PAT tools that require complex multivariate models—are either too slow, insufficiently specific, or operationally burdensome for routine manufacturing use. As facilities move toward digital control, real‑time release testing, and automated operations, the lack of a robust, integration‑ready, CIP‑compatible antibody‑specific PAT tool remains a major barrier to improved process control, reduced product loss, and increased manufacturing efficiency.

Approach

The project provides a next‑generation fiber‑optic probe that integrates engineered fluorescent Protein A‑based ligands with durable surface chemistries to enable continuous, regenerable, real‑time monitoring of IgG and Fc‑fusion proteins across complex downstream matrices. A high‑sensitivity configuration supports rapid detection of early Protein A breakthrough, while a low‑affinity variant extends the measurable range to 5–10 g/L for load‑control and mass‑balance applications. The probe is designed for compatibility with standard downstream regeneration buffers, 0.1 M NaOH CIP, PG13.5 hardware formats, and digital DCS interfaces, while rigorous CIP‑cycle testing, leachables/extractables profiling, gamma‑sterilization studies, and partner‑site demonstrations ensure industrial readiness and BRL advancement

Value Statement/Outcomes

By delivering a low‑cost, molecule‑specific PAT probe with fast response times, CIP compatibility, and integration‑ready interfaces, this project will significantly enhance process control, resin utilization, and product‑loss prevention in antibody manufacturing. The technology reduces reliance on slow offline assays, shortens decision‑making cycles, supports automation and continuous downstream processing, and complements existing UV/NIR/Raman PAT tools with an orthogonal, Fc‑specific signal.