Metal Nanoparticle-Loaded Microgels with Selective Permeability for Direct Detection of Small Molecules in Biological Fluids

Abstract

We report a microfluidic strategy for creating semipermeable microgels containing metal nanoparticles to directly detect small molecules included in the solution of large adhesive proteins using surface-enhanced Raman scattering. With a capillary microfluidic device, gold nanoparticle-laden microgels are prepared to have uniform size. The microgels allow diffusion of smaller molecules than mesh size of their gel network while excluding larger molecules. This enables the selective infusion of small analytes onto the surface of gold nanoparticles from the solutions of adhesive proteins, thereby providing high Raman intensity by metal-surface enhancement; otherwise, proteins adsorb the surface, which significantly reduces the intensity. Therefore, this microgel platform enables the direct detection of analytes from biological fluids and obviates complicated pre- or post-treatment of samples. In addition, the microgels are able to be injected into target volume such as vessels or living organisms, which are then either recovered for analysis or potentially analyzed in situ. This simple but pragmatic method will provide new opportunity in a wide range of molecular detection applications based on Raman spectrum.

Microfluidic Designing Microgels Containing Highly Concentrated Gold Nanoparticles for SERS Analysis of Complex Fluids

“…Therefore, the LOD is estimated as 10 −10 m . In a comparison, the microgels with Δ C = 0 has the LOD of 10 −8 m according to our previous work, which is two orders of magnitude larger; this is roughly consistent with the intensity enhancement factor of 78.4 for the microgels with the concentration factor of 33.2.…”

“…To study of the influence of BSA, the microgels are suspended in the solution of 10 −7 m R6G only. Raman intensity from unary solution of R6G is comparable with that from binary solution of R6G and BSA, indicating that there is no interruption of BSA for measuring Raman spectrum of R6G; it has been reported that BSA adsorbs on the surface of Au NPs and leads to a drastic reduction of Raman intensity when free Au NPs are directly dispersed in the binary solution of R6G and BSA …”

“…Metal nanoparticles have been loaded in a liposome to prevent the access of large molecules that are impermeable to the lipid bilayer . One of the most pragmatic strategies is to make hydrogel microparticles containing metal nanoparticles, as we have demonstrated . The hydrogel matrix possesses the molecular‐size‐selective permeability as it has a limiting mesh size controllable with a crosslinking density .…”

Nanostructured plasmonic substrates for use as SERS sensors

“…The size-selective separation of analytes is useful for detecting small molecules dispersed in a mixture, such as human blood or commercial beverages. Hydrogels can separate target molecules from a mixture using their small mesh size [ 82 ]. Molecules with a size smaller than the mesh size of the hydrogel can diffuse into a gold nanoparticle-encapsulated hydrogel, whereas larger materials are excluded.…”

Nanogap‐Rich Au Nanowire SERS Sensor for Ultrasensitive Telomerase Activity Detection: Application to Gastric and Breast Cancer Tissues Diagnosis

“…SERS has been considered as an attractive technique for the sensitive and selective detection of biomolecules because of its single molecule level sensitivity, molecular specificity, and insensitivity to quenching . Recently, Yang and co‐workers and Cui and co‐workers reported SERS based telomerase activity detection methods using Au NPs.…”