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Nanoparticles are extensively used for drug delivery applications. One crucial parameter is the nanoparticle degradation rate, which governs the targeted release of drugs and pharmacokinetics. Optimizing the rate of degradation is a crucial challenge that requires accurate nano-characterization methods. Here we present on-chip microscopy-based techniques to quantify nanoparticle degradation. The lensfree holographic on-chip microscope that was used for this purpose consists of a set of individually-controlled fiber-coupled LEDs, a band-pass filter, a CMOS imager and a temperature controlled polyethylene-glycol reservoir. This mobile microscope captures a set of sub-pixel shifted holograms by turning on/off individual LEDs, where each nanoparticle hologram is significantly enhanced using self-assembled polyethylene-glycol nanolenses. These shifted holograms are used to synthesize a pixel super-resolved hologram, which is then reconstructed to obtain the phase image of the nanoparticles, containing their size information with a sizing accuracy of ±11 nm. Using this technique we quantified three types of growth-factor loaded nanoparticles, i.e., degradable, partially-degradable and non-degradable. By sampling a subset of the particles undergoing degradation at discrete time points, we observed a drastic reduction in the size of the degradable nanoparticles in <10 min, whereas the others did not show any major change till ~24 hours. As an alternative approach, we also created of a sandwich assay by placing a protease-coated coverslip on the nanoparticle/nanolens complex and monitored the particle degradation in real-time. These approaches provide a cost-effective and high-throughput platform to monitor the degradation process of nanoparticles using a sample volume that is >3 orders-of-magnitude smaller than other techniques.
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