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Lab-on-Valve Automated and Miniaturized Assessment of Nanoparticle Concentration Based on Light-Scattering.

Sara S Marques1, Inês I Ramos1, Carla Silva2,3

  • 1LAQV, REQUIMTE, University of Porto, Department of Chemical Sciences, Faculty of Pharmacy, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.

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A new automated lab-on-valve method quickly quantifies nanoparticle (NP) concentration using light scattering. This rapid, low-volume technique supports nanocarrier development and quality control for drug delivery applications.

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Area of Science:

  • Mesofluidics and Nanotechnology
  • Analytical Chemistry and Quality Control

Background:

  • Accurate nanoparticle (NP) concentration is critical for nanocarrier dose determination, drug delivery efficacy, and manufacturing quality control.
  • Existing methods for NP quantification are often slow, require skilled operators, and involve complex post-analysis calculations, hindering research and development.
  • There is a need for faster, simpler, and automated NP quantification techniques to support the development of nanomedicines.

Purpose of the Study:

  • To establish a miniaturized, automated ensemble method for rapid NP concentration measurement using a lab-on-valve (LOV) mesofluidic platform.
  • To validate the method's accuracy, throughput, and suitability for various polymeric nanoparticles, including those intended for drug delivery.

Main Methods:

  • Development of an automated LOV system for sample handling and delivery to the detection unit via flow programming.
  • NP concentration determination based on light transmission decrease caused by light scattering from NPs in the optical path.
  • Analysis of polystyrene and PEG-PLGA nanoparticles, including drug-loaded formulations, using particle tracking analysis (PTA) for validation.

Main Results:

  • The automated LOV method achieved NP concentration measurements in 2 minutes per sample, yielding a throughput of 30 h-1.
  • The system required only 30 μL of sample and accurately quantified polystyrene and PEG-PLGA NPs within the 108-1012 particles mL-1 range.
  • Measurements of drug-loaded PEG-PLGA NPs in simulated physiological fluids showed high recovery (102-115%), confirmed by PTA, demonstrating method robustness.

Conclusions:

  • The developed miniaturized automated LOV method provides a fast, efficient, and precise tool for quantifying nanoparticle concentrations.
  • This technique is suitable for quality control and developmental stages of nanocarriers, particularly polymeric NPs for drug delivery.
  • The method's ability to handle complex samples, like drug-loaded NPs in simulated fluids, highlights its potential to accelerate nanomedicine research and validation.