Towards a point-of-care test to cover atto-femto and pico-nano molar concentration ranges in interleukin 6 detection exploiting PMMA-based plasmonic biosensor chips.

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required. In this work, two IL-6 biosensors are obtained by exploiting the combination of the same antibody self-assembled monolayer with two different plasmonic probes. This approach has demonstrated, via experimental results, that two different IL-6 concentration ranges can be explored. More specifically, IL-6 in an atto-femto molar range can be detected via polymer-based nanoplasmonic chips. On the other hand, a pico-nano molar range is obtained by a surface plasmon resonance platform in plastic optical fibers. As a proof of concept, the detection of IL-6 at the femto molar range has been obtained in Saliva and Serum. The results show that the proposed sensing approach could be useful in developing Point-of-Care devices based on a general setup with the capability to exploit both the plasmonic biosensor chips to monitor the IL-6 in the concentration range of interest, to provide an important support for the diagnosis and monitoring of oral and systemic diseases.

A Review of Apta-POF-Sensors: The Successful Coupling between Aptamers and Plastic Optical Fibers for Biosensing Applications

Aptamers represent the next frontier as biorecognition elements in biosensors thanks to a smaller size and lower molecular weight with respect to antibodies, more structural flexibility with the possibility to be regenerated, reduced batch-to-batch variation, and a potentially lower cost. Their high specificity and small size are particularly interesting for their application in optical biosensors since the perturbation of the evanescent field are low. Apart from the conventional plasmonic optical sensors, platforms based on silica and plastic optical fibers represent an interesting class of devices for point-of-care testing (POCT) in different applications. The first example of the coupling between aptamers and silica optical fibers was reported by Pollet in 2009 for the detection of IgE molecules. Six years later, the first example was published using a plastic optical fiber (POF) for the detection of Vascular Endothelial Growth Factor (VEGF). The excellent flexibility, great numerical aperture, and the large diameter make POFs extremely promising to be coupled to aptamers for the development of a sensitive platform easily integrable in portable, small-size, and simple devices. Starting from silica fiber-based surface plasmon resonance devices, here, a focus on significant biological applications based on aptamers, combined with plasmonic-POF probes, is reported.

SARS-CoV-2 spike protein detection through a plasmonic D-shaped plastic optical fiber aptasensor.

A specific aptameric sequence has been immobilized on short polyethyleneglycol (PEG) interface on gold nano-film deposited on a D-shaped plastic optical fiber (POFs) probe, and the protein binding has been monitored exploiting the very sensitive surface plasmon resonance (SPR) phenomenon. The receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein has been specifically used to develop an aptasensor. Surface analysis techniques coupled to fluorescence microscopy and plasmonic analysis have been utilized to characterize the biointerface. Spanning a wide protein range (25 ÷ 1000 nM), the SARS-Cov-2 spike protein was detected with a Limit of Detection (LoD) of about 37 nM. Different interferents (BSA, AH1N1 hemagglutinin protein and MERS spike protein) have been tested confirming the specificity of our aptasensor. Finally, a preliminary test in diluted human serum encouraged its application in a point-of-care device, since POF-based aptasensor represent a potentially low-cost compact biosensor, characterized by a rapid response, a small size and could be an ideal laboratory portable diagnostic tool.

Proof of Concept for a Quick and Highly Sensitive On-Site Detection of SARS-CoV-2 by Plasmonic Optical Fibers and Molecularly Imprinted Polymers.

The rapid spread of the Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen has generated a huge international public health emergency. Currently the reference diagnostic technique for virus determination is Reverse Transcription Polymerase Chain Reaction (RT-PCR) real time analysis that requires specialized equipment, reagents and facilities and typically 3-4 h to perform. Thus, the realization of simple, low-cost, small-size, rapid and point-of-care diagnostics tests has become a global priority. In response to the current need for quick, highly sensitive and on-site detection of the SARS-CoV-2 virus in several aqueous solutions, a specific molecularly imprinted polymer (MIP) receptor has been designed, realized, and combined with an optical sensor. More specifically, the proof of concept of a SARS-CoV-2 sensor has been demonstrated by exploiting a plasmonic plastic optical fiber sensor coupled with a novel kind of synthetic MIP nano-layer, especially designed for the specific recognition of Subunit 1 of the SARS-CoV-2 Spike protein. First, we have tested the effectiveness of the developed MIP receptor to bind the Subunit 1 of the SARS-CoV-2 spike protein, then the results of preliminary tests on SARS-CoV-2 virions, performed on samples of nasopharyngeal (NP) swabs in universal transport medium (UTM) and physiological solution (0.9% NaCl), were compared with those obtained with RT-PCR. According to these preliminary results, the sensitivity of the proposed optical-chemical sensor proved to be higher than the RT-PCR one. Furthermore, a relatively fast response time (about 10 min) to the virus was obtained without the use of additional reagents.