Shrinkable Hydrogel-Enhanced Biomarker Detection with X-ray Fluorescent Nanoparticles

This paper reports a new method to enhance the sensitivity of nanoparticle-based protein detection with X-ray fluorescence by exploiting the large volume reduction of hydrogel upon dehydration. A carboxylated agarose hydrogel with uniaxial microchannels is used to allow rapid diffusion of nanoparticles and biomolecules into the hydrogel and water molecules out of the hydrogel. Carboxylated hydrogels are modified to capture protein biomarkers and X-ray fluorescence nanoparticles (iron oxide nanoparticles) are modified with antibodies that are specific to protein biomarkers. The presence of protein biomarkers in solution binds the nanoparticles on the hydrogel channels. The dehydration of hydrogels leads to a size reduction of over 80 times, which increases the number of nanoparticles in the interaction volume of the primary X-ray beam and the intensity of characteristic X-ray fluorescence signal. A detection limit of 2 μg/mL for protein detection has been established by determining the number of nanoparticles using X-ray fluorescence.