A Fiber Optic Interface Coupled to Nanosensors: Applications to Protein Aggregation and Organic Molecule Quantification

Daichi Kozawa, Soo Yeon Cho, Xun Gong, Freddy T. Nguyen, Xiaojia Jin, Michael A. Lee, Heejin Lee, Alicia Zeng, Gang Xue, Jeff Schacherl, Scott Gibson, Leonela Vega, Michael S. Strano

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Fluorescent nanosensors hold promise to address analytical challenges in the biopharmaceutical industry. The monitoring of therapeutic protein critical quality attributes such as aggregation is a long-standing challenge requiring low detection limits and multiplexing of different product parameters. However, general approaches for interfacing nanosensors to the biopharmaceutical process remain minimally explored to date. Herein, we design and fabricate a integrated fiber optic nanosensor element, measuring sensitivity, response time, and stability for applications to the rapid process monitoring. The fiber optic-nanosensor interface, or optode, consists of label-free nIR fluorescent single-walled carbon nanotube transducers embedded within a protective yet porous hydrogel attached to the end of the fiber waveguide. The optode platform is shown to be capable of differentiating the aggregation status of human immunoglobulin G, reporting the relative fraction of monomers and dimer aggregates with sizes 5.6 and 9.6 nm, respectively, in under 5 min of analysis time. We introduce a lab-on-fiber design with potential for at-line monitoring with integration of 3D-printed miniaturized sensor tips having high mechanical flexibility. A parallel measurement of fluctuations in laser excitation allows for intensity normalization and significantly lower noise level (3.7 times improved) when using lower quality lasers, improving the cost effectiveness of the platform. As an application, we demonstrate the capability of the fully integrated lab-on-fiber system to rapidly monitor various bioanalytes including serotonin, norepinephrine, adrenaline, and hydrogen peroxide, in addition to proteins and their aggregation states. These results in total constitute an effective form factor for nanosensor-based transducers for applications in industrial process monitoring.

Original languageEnglish
Pages (from-to)10141-10152
Number of pages12
JournalACS Nano
Volume14
Issue number8
DOIs
StatePublished - 25 Aug 2020
Externally publishedYes

Keywords

  • antibody
  • biopharmaceutical monitoring
  • carbon nanotube
  • lab on fiber
  • optode fiber
  • protein aggregation

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