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 labelfree 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.

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The relation between the electronegativity Z of an atom or an ion (Z=-OE(Z, N)/c?N) and its finite difference (Mulliken like) counterpart has been studied for the elements of the groups IA to VIIA of the Periodic Table, using an approximate Density Functional Theory. Only the valence electrons are taken into account and the effect of the ionic core is simulated by a simple empty core pseudopotential. The first derivative ~z/ON of the electronegativity has also been computed. The interest in Z and ~Z/~?N is illustrated by a simple model for the transfer of electronic charge in a molecule. Molecular electronegativities are then computed.