H³ (Hydrogel‐Based, High‐Sensitivity, Hybrid) Plasmonic Transducers for Biomolecular Interactions Monitoring

Abstract

more complex systems, such as microelectronics and microfluidics, without compromising high sensitivity and mass production. [5] Among the many available polymeric materials, hydrogels represent the ideal substrates for plasmonic sensors due to their optical transparency, biocompatibility, and their swelling capability in presence of an aqueous environment. [6][7][8] Hydrogels are generally recognized as 3D architectures, whose crosslinking density, mesh network size, and polymerization agent can be tuned and selected according to the desired applications. Moreover, they can be easily engineered and made responsive to external stimuli, [9] this being crucial when designing analytical platforms with applications in biochemical sensing. [8,10] In this context, when properly assembled and functionalized, noble metal nanoparticles (NPs), basically silver (Ag), and gold (Au), represent the ideal transducers since they can show a dramatically high response upon exposure to a target analyte. In some cases, the transduction is visible to the naked eye, especially in liquid colorimetric assays, which exploit the capability of plasmonic nanoparticles to aggregate, undergoing deep color variations. [11][12][13] Even if very effective and similar to the Enzyme-Linked Immunosorbent Assay (ELISA) commercial kits, the liquid phase plasmonic assays could suffer from pH, ionic strength, and temperature both during the preparation of the assay and the measurement procedure itself. [14][15][16] To overcome these limitations without giving up the sensing advantages provided by plasmonic nanoparticles, both top-down and bottom-up fabrication strategies have been proposed to arrange them in periodic, quasiperiodic, and random arrays on different substrates. [17][18][19] Different transduction mechanisms have been proposed to design plasmonic biochemical sensors and to ensure high sensitivity and specificity. However, portability and ease of use of these optical devices still represent a hard-to-solve challenge. All these transduction mechanisms are based on the localized surface plasmon resonance (LSPR) exhibited by noble-metal NPs. [20,21] Refractometric biosensors exploit the LSPR shifts as a function of a target analyte when properly interacting with the biorecognition element adhered on the surface of the NPs; [22,23] Surface-enhanced infrared absorption (SEIRA) and surface-enhanced raman scattering (SERS) exploit the LSPR to enhance infrared and Raman signals of molecules onto plasmonic substrates; [24][25][26] Metal-enhanced fluorescence (MEF), also referred to as plasmon-enhanced fluorescence A hybrid plasmonic transducer made of a Poly-(ethylene glycol) diacrylate (PEGDA) hydrogel and citrate gold nanoparticles detects the biotin-streptavidin interaction at picomolar (× 10 −12 m ) concentrations. The all-solution fabrication strategy, herein proposed, is large-scale, easily tunable, and low-cost; nevertheless, this innovative device is highly reproducible and optically stable, and it can be used in dual-optical mode. Indeed, b...

Plasmonic Nanosensors: Design, Fabrication, and Applications in Biomedicine

“…Moreover, a 3D structure could be generated by the photothermal fabrication of a thermo-crosslinking material as the poly(NIPAM-co-acrylic acid derivative) hydrogels [156]. Sensing with plasmonic hydrogel nanocomposites can be achieved by exploiting all the sensing mechanisms highlighted in the previous sections: the sensitivity to RI in the immediate NPs surroundings [157,158], the NPs aggregation in LSPR-based sensing [25,159], the SERS effect for a label-free detection [160], or the MEF mechanism for labeled biomolecules [36]. As stated in the previous sections, in LSPR sensing, gold NPs are usually preferred to silver NPs because they generally show a lower oxidative susceptibility than Ag NPs, which occur when they come in contact with solvents and biomolecules [21,161].…”

“…Moreover, the optical detection of biotin was proved by modifying with a cysteamine the Au NPs embedded into the nanocomposite. Recently, Miranda et al [36] presented another PEGDA-based biosensor containing spherical citrate-gold NPs able to detect the biotin-streptavidin (SA) interaction down to 10 −12 M concentrations. The originality of the sensor pointed to the fabrication strategy that provided a large-scale, versatile, easy, and low-cost biosensing flexible platform with applications in biomedical or environmental diagnostics.…”

“…where I SERS and I Raman stand for the intensities of Raman and SERS signals, respectively, and N SERS and N Raman are the average number of molecules in the scattering volume in each measurement [33]. Differently, metal-enhanced fluorescence induced by plasmonic nanoparticles is still not fully understood, but it strongly depends on (i) the spectral overlap between the plasmon extinction and the excitation (Förster resonance energy transfer (FRET) mechanism) and/or emission (Purcell mechanism) of a fluorescent dye, and (ii) on the distance between the fluorophore/NP couple [34][35][36]. Nanobiosensors using plasmonic NP-based optical transducers can be made in solution (colloids), or by depositing metal nanoparticles on dielectric substrates, creating periodic or non-periodic arrays, or by deposition/embedding on/into polymeric materials.…”

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

“…By combining the polymeric matrix with inorganic materials with suitable optical properties, such as gold or titania nanoparticles, the ISASI researchers fabricated sensors for the detection of specific analytes with label free optical techniques [ 156 , 157 , 158 , 159 ]. The hydrogels, added with a proper photoinitiator, could also be lithographically casted in microneedle arrays this ensure the controlled release of active molecules through the skin [ 160 , 161 , 162 ].…”

Hollow Microneedle‐based Plasmonic Sensor for on Patch Detection of Molecules in Dermal Interstitial Fluid

“…The capability of PEGDA to retain the physical and chemical stability of AuNPs, which act as optical transducers in both label-free and label-based modes, has been already reported in previous works. [39,40] The combination of plasmonic transducers and MNs has been already reported in the literature, [5,41] as a promising optical alternative to electrochemical transducers. However, in the proposed platforms, the plasmonic transducers are arranged outside the MNs arrays.…”