Now that a fully-implantable, continuous glucose monitor has received FDA approval, optical techniques other than fluorescence will seek to overcome the limited lifetimes resulting from photobleaching. Using plasmonic nanoparticles, we present the potential of reversible SERS-active sensing assays to function as long-term implantable sensors. The assays offer high selectivity and specificity of analyte detection and concentration without loss of emission intensity over time due to photodestruction. These assays are encapsulated in microdomains bounded by polyelectrolyte multilayers (PEMs), permeable to the target but impermeable to proteins. The microdomains are stabilized in hydrogels for biocompatibility and longevity. This study characterizes the performance of pH-sensitive Raman probes in three different hydrogels in a simulated in vivo environment with changing pH over time.
Metal nanoparticles conjugated with DNA oligomers have been intensively studied for a variety of applications, including optical diagnostics. Assays based on aggregation of DNA-coated particles in proportion to the concentration of target analyte have not been widely adopted for clinical analysis, however, largely due to the nonspecific responses observed in complex biofluids. While sample pre-preparation such as dialysis is helpful to enable selective sensing, here we sought to prove that assay encapsulation in hollow microcapsules could remove this requirement and thereby facilitate more rapid analysis on complex samples. Gold nanoparticle-based assays were incorporated into capsules comprising polyelectrolyte multilayer (PEMs), and the response to small molecule targets and larger proteins were compared. Gold nanoparticles were able to selectively sense small Raman dyes (Rhodamine 6G) in the presence of large protein molecules (BSA) when encapsulated. A ratiometric based microRNA-17 sensing assay exhibited drastic reduction in response after encapsulation, with statistically-significant relative Raman intensity changes only at a microRNA-17 concentration of 10 nM compared to a range of 0-500 nM for the corresponding solution-phase response.
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