Nanofluidic device for continuous multiparameter quality assurance of biologics
- 22 May 2017
- journal article
- Published by Springer Science and Business Media LLC in Nature Nanotechnology
- Vol. 12 (8), 804-812
- https://doi.org/10.1038/nnano.2017.74
Abstract
Process analytical technology (PAT) is critical for the manufacture of high-quality biologics as it enables continuous, real-time and on-line/at-line monitoring during biomanufacturing processes. The conventional analytical tools currently used have many restrictions to realizing the PAT of current and future biomanufacturing. Here we describe a nanofluidic device for the continuous monitoring of biologics' purity and bioactivity with high sensitivity, resolution and speed. Periodic and angled nanofilter arrays served as the molecular sieve structures to conduct a continuous size-based analysis of biologics. A multiparameter quality monitoring of three separate commercial biologic samples within 50 minutes has been demonstrated, with 20 µl of sample consumption, inclusive of dead volume in the reservoirs. Additionally, a proof-of-concept prototype system, which integrates an on-line sample-preparation system and the nanofluidic device, was demonstrated for at-line monitoring. Thus, the system is ideal for on-site monitoring, and the real-time quality assurance of biologics throughout the biomanufacturing processes.Keywords
This publication has 38 references indexed in Scilit:
- Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiativeBiotechnology Advances, 2009
- Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritisNature Reviews Rheumatology, 2009
- Safety-Related Regulatory Actions for Biologicals Approved in the United States and the European UnionPublished by American Medical Association (AMA) ,2008
- (Re)defining biopharmaceuticalNature Biotechnology, 2008
- Protein therapeutics: a summary and pharmacological classificationNature Reviews Drug Discovery, 2008
- Early Development of Therapeutic Biologics - PharmacokineticsCurrent Drug Metabolism, 2006
- Protein drug stability: a formulation challengeNature Reviews Drug Discovery, 2005
- Biologic and therapeutic role of HER2 in cancerOncogene, 2003
- Instability, stabilization, and formulation of liquid protein pharmaceuticalsInternational Journal of Pharmaceutics, 1999
- Expression in Escherichia coli of chemically synthesized genes for human insulin.Proceedings of the National Academy of Sciences of the United States of America, 1979