Silica Inverse Opal Nanostructured Sensors for Enhanced Immunodetection of Extracellular Vesicles by Quartz Crystal Microbalance with Dissipation Monitoring

Abstract

Extracellular vesicles (EVs) are nanosized circulating assemblies that contain biomarkers considered promising for early diagnosis within neurology, cardiology, and oncology. Recently, acoustic wave biosensors, in particular based on quartz crystal microbalance with dissipation monitoring (QCM-D), have emerged as a sensitive, label-free, and selective EV characterization platform. A rational approach to further improving sensing detection limits relies on the nanostructuration of the sensor surfaces. To this end, inorganic inverse opals (IOs) derived from colloidal self-assembly present a highly tunable and scalable nanoarchitecture of suitable feature sizes and surface chemistry. This work systematically investigates their use in two-dimensional (2D) and three-dimensional (3D) for enhanced QCM-D EV detection. Precise tuning of the architecture parameters delivered improvements in detection performance to sensitivities as low as 6.24 × 10 7 particles/mL. Our findings emphasize that attempts to enhance acoustic immunosensing via increasing the surface area by 3D nanostructuration need to be carefully analyzed in order to exclude solvent and artifact entrapment effects. Moreover, the use of 2D nanostructured electrodes to compartmentalize analyte anchoring presents a particularly promising design principle.

Amplified EQCM-D detection of extracellular vesicles using 2D gold nanostructured arrays fabricated by block copolymer self-assembly

“…[9][10][11] Until now, nanostructuration of QCM-D sensor surfaces has been focused on creating 3D porous structures such as anodic aluminium oxide or inverse opals, showing promising results in improving analytical response against different targets, such as enzymes, liposomes, and antibodies. [12][13][14][15] However, those nanofabrication methodologies are limited in providing access to tailored, reproducible, and precisely controlled structures, preventing full exploitation for clinical applications. Moreover, the use of porous thin films can lead to solvent and artefact entrapment effects in the nanostructured film, hindering data interpretation and introducing uncertainty over obtained results.…”

Nature-inspired functional porous materials for low-concentration biomarker detection

“…Other body fluids, such as sweat or saliva, are an attractive alternative to blood, 5 but they contain significantly less glucose and would thus require a much higher sensor sensitivity to produce a detectable signal. Nanostructured materials can provide novel approaches for sensor development thanks to their large surface area, [6][7][8][9][10] which allows for both miniaturization of the final device and for the decrease of the detection limit. Regarding inorganic materials, examples in the literature are mainly based on the use of nanoparticles, [11][12][13] nanowires, 14 nanotubes, 15,16 and nanosheet 17 architectures.…”

“…IOs, initially used to replicate the structural coloration occurring in nature, both in the inanimate and animate world, 10,21 possess ideal features to be used as materials for sensor development. 9,10,22,23 The typical order of the IO structure poses significant advantages over the use of other porous, less ordered materials such as foams and mesoporous silica since the complete interconnectivity of the pores allows us to exploit the whole area for surface-based processes. This characteristic has become fundamental for sensing applications, as it facilitates the transport of the target analyte to the active surface and improves the signal measured, where the LOD was 5 mM.…”

“…Nanostructured materials can provide novel approaches for sensor development thanks to their large surface area, 6–10 which allows for both miniaturization of the final device and for the decrease of the detection limit. Regarding inorganic materials, examples in the literature are mainly based on the use of nanoparticles, 11–13 nanowires, 14 nanotubes, 15,16 and nanosheet 17 architectures.…”

Core–Shell Silica Nanoparticle-Based Barcodes Combined with a Hybridization Chain Reaction for Multiplex Quantitative Detection of Bacterial Drug-Resistance Genes

“…Of specific interest here, PhCs can be employed as templates to fabricate inverse opals. 25 By filling the templates with hydrogel and then removing the templates, the obtained hydrogel inverse opals also have bright central highlights and structural colors as PhCs. 26 However, the different swelling degrees of the hydrogel in different solutions will cause the structural color to change, resulting in unstable encoding.…”