Nanoplasmonic Biosensor Research Articles

Sample-to-answer point-of-care testing platform for quantitative detection of small molecules in blood using a smartphone-and microfluidic-based nanoplasmonic biosensor

Rapid and ultrasensitive detection of small molecules is of great significance in point-of-care testing (POCT) for health management and biomarker detection for many diseases. In this study, a novel POCT device integrated with a metasurface plasmon resonance (MetaSPR) chip with diffusion film enhancement was designed and controlled by a smartphone app for small molecule ultrasensitive detection based on competitive immunoassays. In this method, the sample competes with the antigen immobilized on the chip, and labeled antibodies are pumped from the sample pad to the chip for multiplexed and sample-to-answer analysis of blood. The entire process of detection is 14.3-fold less time (210 s in total) compared to an enzyme-linked immunosorbent assay (ELISA). For this assay, the limit of detection was 0.36 ppt and 1.05 ppt for testosterone and 25-hydroxyvitamin D3, respectively, and showed 100- to 1000-fold greater sensitivity than that of ELISA. Collectively, the data suggest that this novel POCT platform, based on a MetaSPR biosensor, provides ultrasensitive, rapid, regenerable, versatile, and real-time quantitative analysis for applications in health management and early diagnosis.

Waveguide-Enhanced Nanoplasmonic Biosensor for Ultrasensitive and Rapid DNA Detection.

DNA is fundamental for storing and transmitting genetic information. Analyzing DNA or RNA base sequences enables the identification of genetic disorders, monitoring gene expression, and detecting pathogens. Traditional detection techniques like polymerase chain reaction (PCR) and next-generation sequencing (NGS) have limitations, including complexity, high cost, and the need for advanced computational skills. Therefore, there is a significant demand for enzyme-free and amplification-free strategies for rapid, low-cost, and sensitive DNA detection. DNA biosensors, especially those utilizing plasmonic nanomaterials, offer a promising solution. This study introduces a novel DNA-functionalized waveguide-enhanced nanoplasmonic optofluidic biosensor using a nanogold-linked sorbent assay for enzyme-free and amplification-free DNA detection. Integrating plasmonic gold nanoparticles (AuNPs) with a glass planar waveguide (WG) and a microfluidic channel, fabricated through cost-effective, vacuum-free methods, the biosensor achieves specific detection of complementary target DNA sequences. Utilizing a sandwich architecture, AuNPs labeled with detection DNA probes enhance sensitivity by altering evanescent wave distribution and inducing plasmon resonance modes. The biosensor demonstrated exceptional performance in DNA detection, achieving a limit of detection (LOD) of 33.1 fg/mL (4.36 fM) with a rapid response time of approximately 8 min. This ultrasensitive, rapid, and cost-effective biosensor exhibits minimal background nonspecific adsorption, making it highly suitable for clinical applications and early disease diagnosis. The innovative design and fabrication processes offer significant advantages for mass production, presenting a viable tool for precise disease diagnostics and improved clinical outcomes.

Advancing SARS‐CoV‐2 Variant Detection with High Affinity Monoclonal Antibodies and Plasmonic Nanostructure

AbstractA nanoplasmonic biosensor for the precise detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by leveraging advances in nanostructured sensing materials and highly selective monoclonal antibodies is presented. The sensor integrates plasmonic Au nanostructures optimized for surface‐enhanced Raman scattering (SERS), enhancing sensitivity through unique light interactions at the nanoscale. Coupled with exclusive antibodies that specifically target SARS‐CoV‐2 and its evolving variants, this sensor demonstrates remarkable selectivity and versatility. Validated with 270 clinical samples, it demonstrates a sensitivity of 98.9% and specificity of 100%. More importantly, the virus in nasopharyngeal swab samples collected over 3 years, marking the long‐term, large‐scale clinical validation of the nanoplasmonic biosensor for SARS‐CoV‐2 is been successfully detected. Furthermore, the integration of this sensor with face masks enables the detection of airborne SARS‐CoV‐2, highlighting its potential for routine management of coronavirus disease 2019 (COVID‐19).

Pollen-based natural nanostructures to realize nanoplasmonic biochips for single-molecule detection

In this work, a paradigm change in the development of the plasmonic-based bio/chemical sensing approaches is presented. The proposed idea is to use natural nanostructures instead of those fabricated by electron-beam lithography (EBL) tools. This sensing approach produces several advantages, such as high performances without an optimization step and a simple, low-cost, and eco-friendly production process with respect to other methods, which are still time-consuming with low scalability. In particular, pollen's nanostructures covered by gold nanofilms are used to realize gold nanogratings (GNG), similar to those made via EBL, to excite hybrid plasmonic phenomena. Bulk and binding sensitivities are evaluated and compared to nanoplasmonic sensors, particularly those achieved via an EBL-based chip. As proof of principle, an estrogen receptor (ERα) is immobilized on the plasmonic nanostructured surfaces of both EBL-based and pollen-based chips and interrogated by the same custom 3D-printed holder through a transmission-based experimental setup, exploiting polymer optical fibers (POFs). The experimental results demonstrate that the proposed pollen-based nanoplasmonic biosensor shows performance very similar to an EBL-based nanoplasmonic biosensor, indicating the equivalence between the two nanoplasmonic biosensors. The biosensor exhibited a detection limit better than 1 aM for the estradiol, demonstrating the capabilities of the proposed sensing approach towards single-molecule detection.

Nanoplasmonic biosensors for environmental sustainability and human health.

Monitoring the health conditions of the environment and humans is essential for ensuring human well-being, promoting global health, and achieving sustainability. Innovative biosensors are crucial in accurately monitoring health conditions, uncovering the hidden connections between the environment and human well-being, and understanding how environmental factors trigger autoimmune diseases, neurodegenerative diseases, and infectious diseases. This review evaluates the use of nanoplasmonic biosensors that can monitor environmental health and human diseases according to target analytes of different sizes and scales, providing valuable insights for preventive medicine. We begin by explaining the fundamental principles and mechanisms of nanoplasmonic biosensors. We investigate the potential of nanoplasmonic techniques for detecting various biological molecules, extracellular vesicles (EVs), pathogens, and cells. We also explore the possibility of wearable nanoplasmonic biosensors to monitor the physiological network and healthy connectivity of humans, animals, plants, and organisms. This review will guide the design of next-generation nanoplasmonic biosensors to advance sustainable global healthcare for humans, the environment, and the planet.

Nanoplasmonic Single-Tumoroid Microarray for Real-Time Secretion Analysis.

Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine as such 3D structures grown from tumor cells recapitulate better tumor characteristics, making these tumoroids unique for personalized cancer research. Assessment of their functional behavior, particularly protein secretion, is of significant importance to provide comprehensive insights. Here, a label-free spectroscopic imaging platform is presented with advanced integrated optofluidic nanoplasmonic biosensor that enables real-time secretion analysis from single tumoroids. A novel two-layer microwell design isolates tumoroids, preventing signal interference, and the microarray configuration allows concurrent analysis of multiple tumoroids. The dual imaging capability combining time-lapse plasmonic spectroscopy and bright-field microscopy facilitates simultaneous observation of secretion dynamics, motility, and morphology. The integrated biosensor is demonstrated with colorectal tumoroids derived from both cell lines and patient samples to investigate their vascular endothelial growth factor A (VEGF-A) secretion, growth, and movement under various conditions, including normoxia, hypoxia, and drug treatment. This platform, by offering a label-free approach with nanophotonics to monitor tumoroids, can pave the way for new applications in fundamental biological studies, drug screening, and the development of therapies.

A novel biomimetic nanoplasmonic sensor for rapid and accurate evaluation of checkpoint inhibitor immunotherapy.

Immune checkpoint inhibitors (ICIs) emerged as promising immunotherapies for cancer treatment, harnessing the patient's immune system to fight and eliminate tumor cells. However, despite their potential and proven efficacies, checkpoint inhibitors still face important challenges such as the tumor heterogeneity and resistance mechanisms, and the complex in vitro testing, which limits their widespread applicability and implementation to treat cancer. To address these challenges, we propose a novel analytical technique utilizing biomimetic label-free nanoplasmonic biosensors for rapid and reliable screening and evaluation of checkpoint inhibitors. We have designed and fabricated a low-density nanostructured plasmonic sensor based on gold nanodisks that enables the direct formation of a functional supported lipid bilayer, which acts as an artificial cell membrane for tumor ligand immobilization. With this biomimetic scaffold, our biosensing approach provides real-time, highly sensitive analysis of immune checkpoint pathways and direct assessment of the blocking effects of monoclonal antibodies in less than 20min/test. We demonstrate the accuracy of our biomimetic sensor for the study of the programmed cell death protein 1 (PD1) checkpoint pathway, achieving a limit of detection of 6.7ng/mL for direct PD1/PD-L1 interaction monitoring. Besides, we have performed dose-response inhibition curves for an anti-PD1 monoclonal antibody, obtaining a half maximal inhibitory concentration (IC50) of 0.43nM, within the same range than those obtained with conventional techniques. Our biomimetic sensor platform combines the potential of plasmonic technologies for rapid label-free analysis with the reliability of cell-based assay in terms of ligand mobility. The biosensor is integrated in a compact user-friendly device for the straightforward implementation in biomedical and pharmaceutical laboratories.

Advances in Nanoplasmonic Biosensors: Optimizing Performance for Exosome Detection Applications.

The development of sensitive and specific exosome detection tools is essential because they are believed to provide specific information that is important for early detection, screening, diagnosis, and monitoring of cancer. Among the many detection tools, surface-plasmon resonance (SPR) biosensors are analytical devices that offer advantages in sensitivity and detection speed, thereby making the sample-analysis process faster and more accurate. In addition, the penetration depth of the SPR biosensor, which is <300 nm, is comparable to the size of the exosome, making the SPR biosensor ideal for use in exosome research. On the other hand, another type of nanoplasmonic sensor, namely a localized surface-plasmon resonance (LSPR) biosensor, has a shorter penetration depth of around 6 nm. Structural optimization through the addition of supporting layers and gap control between particles is needed to strengthen the surface-plasmon field. This paper summarizes the progress of the development of SPR and LSPR biosensors for detecting exosomes. Techniques in signal amplification from two sensors will be discussed. There are three main parts to this paper. The first two parts will focus on reviewing the working principles of each sensor and introducing several methods that can be used to isolate exosomes. This article will close by explaining the various sensor systems that have been developed and the optimizations carried out to obtain sensors with better performance. To illustrate the performance improvements in each sensor system discussed, the parameters highlighted include the detection limit, dynamic range, and sensitivity.

Combating Prozone Effects and Predicting the Dynamic Range of Naked-Eye Nanoplasmonic Biosensors through Capture Bioentity Optimization.

Accurately quantifying high analyte concentrations poses a challenge due to the common occurrence of the prozone or hook effect within sandwich assays utilized in plasmonic nanoparticle-based lateral flow devices (LFDs). As a result, LFDs are often underestimated compared to other biosensors with concerns surrounding their specificity and sensitivity toward the target analyte. To address this limitation, here we develop an analytical model capable of predicting the prozone effect and subsequently the dynamic range of the biosensor based on the concentration of the capture antibody. To support our model, we conduct a sandwich immunoassay to detect C-reactive protein (CRP) in a phosphate-buffered saline (PBS) buffer using an LFD. Within the experiment, we investigate the relationship between the CRP dynamic range and the prozone effect as a function of the capture antibody concentration, which is increased from 0.1 to 2 mg/mL. The experimental results, while supporting the developed analytical model, show that increasing the capture antibody concentration increases the dynamic range. The developed model therefore holds the potential to expand the measurable range and reduce costs associated with quantifying biomarkers in diverse diagnostic assays. This will ultimately allow LFDs to have better clinical significance before the prozone effect becomes dominant.

Exosome Isolation and Detection: From Microfluidic Chips to Nanoplasmonic Biosensor.

Exosomes are becoming more widely acknowledged as significant circulating indicators for the prognosis and diagnosis of cancer. Circulating exosomes are essential to the development and spread of cancer, according to a growing body of research. Using existing technology, characterizing exosomes is quite difficult. Therefore, a direct, sensitive, and targeted approach to exosome detection will aid in illness diagnosis and prognosis. The review discusses the new strategies for exosome isolation and detection technologies from microfluidic chips to nanoplasmonic biosensors, analyzing the advantages and limitations of these new technologies. This review serves researchers to better understand exosome isolation and detection methods and to help develop better exosome isolating and detecting devices for clinical applications.

Ultrasensitive and Rapid Detection of Procalcitonin via Waveguide-Enhanced Nanogold-Linked Immunosorbent Assay for Early Sepsis Diagnosis.

Sepsis, a life-threatening inflammatory response, demands economical, accurate, and rapid detection of biomarkers during the critical "golden hour" to reduce the patient mortality rate. Here, we demonstrate a cost-effective waveguide-enhanced nanogold-linked immunosorbent assay (WENLISA) based on nanoplasmonic waveguide biosensors for the rapid and sensitive detection of procalcitonin (PCT), a sepsis-related inflammatory biomarker. To enhance the limit of detection (LOD), we employed sandwich assays using immobilized capture antibodies and detection antibodies conjugated to gold nanoparticles to bind the target analyte, leading to a significant evanescent wave redistribution and strong nanoplasmonic absorption near the waveguide surface. Experimentally, we detected PCT for a wide linear response range of 0.1 pg/mL to 1 ng/mL with a record-low LOD of 48.7 fg/mL (3.74 fM) in 8 min. Furthermore, WENLISA has successfully identified PCT levels in the blood plasma of patients with sepsis and healthy individuals, offering a promising technology for early sepsis diagnosis.

A simple and rapid colorimetric detection of Staphylococcus aureus relied on the distance-dependent optical properties of silver nanoparticles.

The quick and accurate diagnosis of pathogens has appeared as a pressing issue in clinical diagnostics, environmental monitoring, and food safety. The available assays are suffering from limited capacities in simple, fast, low-cost, and on-site detection to increase prevention and proper treatment. Herein, we address these challenges by developing a simple, speedy, affordable, and ultrasensitive nanoplasmonic biosensor for colorimetric detection of cDNA from staphylococcal RNA relying on the distance-dependent optical features of silver nanostructures for the measurement of color variations and spectral shifts owing to the plasmon coupling generated by the cross-linking accumulation of AgNPs. The method described utilizes silver nanoparticles (AgNPs) immobilized with two different single-stranded oligonucleotides (ssDNA1 and ssDNA2) that specifically recognize the target DNA. Sandwich hybridization of target DNA with ssDNA1 and ssDNA2 induced color variations and spectral shifts of AgNPs, whereas test samples without the target DNA remained yellow as the initial color of colloidal silver. The designed nanoplasmonic biosensor demonstrated high specificity with the detection limit (LOD) of ∼1.8 amol target DNA (∼106 molecules per test) in the broad linear dynamic range from 0.01 to 100 nM, and LOD down to a few cells was attained for amplified bacterial nucleic acids and a linear range from 102 CFU mL-1 to 107 CFU mL-1. The sensing approach showed great potential for the timely diagnosis of pathogens in low-density samples, and it has considerable merits over traditional culture approaches and qPCR techniques.

Nanoplasmonic biosensors for multicolor visual analysis of acetylcholinesterase activity and drug inhibitor screening in point-of-care testing

The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the α-FeOOH nanorods (NRs) to release amounts of Fe2+, which was regarded as Fenton reagent to efficiently catalyze H2O2 to produce ·OH. Then, the as-formed ·OH can further largely shorten the gold nanobipyramids (Au NBPs), generating a series of palpable color variations. The linear range for AChE activity was 0.01–500.0 U/L with the limit of detection as low as 0.0074 U/L. The vivid visual effects could be easily distinguished for the multicolor assay of AChE activity by naked eye in visible light. To achieve the point-of-care testing, Au NBPs were further assembled on polymeric electrospun nanofibrous films (ENFs) surface as test strips for the easy-to-use test of AChE activity by RGB values with a smartphone. Fascinatingly, this proposed strategy can be used for the visual screening AChE inhibitors or non-inhibitors. Comparing with the clinical drugs (rivastigmine tartrate, and donepezil), some natural alkaloids such as evodiamine, caffeine, camptothecin, and berberine hydrochloride were selected as inhibitor modes to confirm the drug screening capability of this method. This proposed strategy may have great potential in the other disease-related enzymatic biomarkers assay and the rapid screening of drug therapy.

Development of highly sensitive plasmonic biosensors encoded with gold nanoparticles on M13 bacteriophage networks

In this study, a novel nanoplasmonic substrate is developed for biomedical applications. In nanoplasmonic biosensors, a substrate that can induce strong hot spots by forming uniform nanogaps smaller than 10 nm is required to implement a device capable of detecting biomarkers at low concentrations. Herein, gold nanoparticles-encoded M13 bacteriophage (AuNPs@M13) substrate was developed by immobilizing 60 nm AuNPs onto the surface of an M13 bacteriophage scaffold with a network assembly structure. The plasmonic characteristics of the proposed AuNPs-M13 were evaluated by assessing the nanogap distribution, electromagnetic enhancement effects, and reproducibility of the fabricated substrate. Additionally, an immunoassay for severe acute respiratory syndrome coronavirus 2 was performed to confirm the clinical applicability of the proposed AuNPs@M13 substrate. When the AuNPs@M13 was used as a nanoplasmonic substrate, it was possible to achieve better sensitivity (limit of detection [LoD] = 1.21 PFU/mL) than that with the commercially available lateral flow assay strip (LoD = 300–500 PFU/mL) or enzyme-linked immunoassay (LoD = 48 PFU/mL). The proposed AuNPs@M13 in this study is expected to be used as an innovative biomedical device for the high-sensitivity detection of various biomarkers.

Eco-friendly Synthesis of Silver Nanoparticles and its Application in Hydrogen Photogeneration and Nanoplasmonic Biosensing.

Environmentally friendly methods for silver nanoparticles (AgNPs) synthesis without the use of hazardous chemicals have recently drawn attention. In this work, AgNPs have been synthesized by microwave irradiation using only honey solutions or aqueous fresh pink radish extracts. The concentrations of honey, radish extract, AgNO3 and pH were varied. AgNPs presented mean sizes between 7.0 and 12.8 nm and were stable up to 120 days. The AgNPs were employed as co-catalyst (TiO2 @AgNPs) to increase the hydrogen photogeneration under UV-vis and only visible light irradiation, when compared to pristine TiO2 NPs. The prepared photocatalyst also showed hydrogen generation under visible light. Additionally, AgNPs were used to assemble a nanoplasmonic biosensor for the biodetection of extremely low concentrations of streptavidin, owing to its specific binding to biotin. It is shown here that green AgNPs are versatile nanomaterials, thus being potential candidates for hydrogen photogeneration and biosensing applications.

A plasmonic gold nano-surface functionalized with the estrogen receptor for fast and highly sensitive detection of nanoplastics

Nanoplastics are a global emerging environmental problem whose effects might pose potential threats to the human’s health. Despite the relevance of the issue, fast, reliable and quantitative in situ analytical approaches to determine nanoplastics are not yet available. The aim of this work was to devise an optical sensor with the goal of direct detecting and quantifying nanoplastics in seawater without sample pre-treatments. To this purpose, a nano-plasmonic biosensor was developed by exploiting an Estrogen Receptor (ER) recognition element grafted onto a polymer-based gold nanograting (GNG) plasmonic platform. The ER-GNG biosensor required just minute sample volumes (2 μL), allowed rapid detection (3 min) and enabled to determine nanoplastics in simulated seawater with a linear dynamic concentrations range of 1–100 ng/mL, thus encompassing the expected environmental loads. The nanostructured grating (GNG) provided remarkable performance enhancements, extending the measurement range across five orders of magnitude, thanks to the both the SPR and the localized SPR phenomena occurring at the GNG chip. At last, the ER-GNG biosensor was tested on real seawater samples collected in the Naples area and the results (∼30 ng/mL) were verified by a conventional approach (filtration and evaporation), confirming the ER-GNG sensor offers a straightforward and highly sensitive method for the direct in-field nanoplastics monitoring.

Nanoplasmonic biosensors for precision medicine.

Nanoplasmonic biosensors have a huge boost for precision medicine, which allows doctors to better understand diseases at the molecular level and to improve the earlier diagnosis and develop treatment programs. Unlike traditional biosensors, nanoplasmonic biosensors meet the global health industry's need for low-cost, rapid and portable aspects, while offering multiplexing, high sensitivity and real-time detection. In this review, we describe the common detection schemes used based on localized plasmon resonance (LSPR) and highlight three sensing classes based on LSPR. Then, we present the recent applications of nanoplasmonic in other sensing methods such as isothermal amplification, CRISPR/Cas systems, lab on a chip and enzyme-linked immunosorbent assay. The advantages of nanoplasmonic-based integrated sensing for multiple methods are discussed. Finally, we review the current applications of nanoplasmonic biosensors in precision medicine, such as DNA mutation, vaccine evaluation and drug delivery. The obstacles faced by nanoplasmonic biosensors and the current countermeasures are discussed.

A digital nanoplasmonic microarray immunosensor for multiplexed cytokine monitoring during CAR T-cell therapy from a leukemia tumor microenvironment model

The release of cytokines by chimeric antigen receptor (CAR) T-cells and tumor resident immune cells defines a significant part of CAR T-cell functional activity and patient immune responses during CAR T-cell therapy. However, few studies have so far precisely characterized the cytokine secretion dynamics in the tumor niche during CAR T-cell therapy, which requires multiplexed, and timely biosensing platforms and integration with biomimetic tumor microenvironment. Herein, we implemented a digital nanoplasmonic microarray immunosensor with a microfluidic biomimetic Leukemia-on-a-Chip model to monitor cytokine secretion dynamics during CD19 CAR T-cell therapy against precursor B-cell acute lymphocytic leukemia (B-ALL). The integrated nanoplasmonic biosensors achieved precise multiplexed cytokine measurements with low operating sample volume, short assay time, heightened sensitivity, and negligible sensor crosstalk. Using the digital nanoplasmonic biosensing approach, we measured the concentrations of six cytokines (TNF-α, IFN-γ, MCP-1, GM-CSF, IL-1β, and IL-6) during first 5 days of CAR T-cell treatment in the microfluidic Leukemia-on-a-Chip model. Our results revealed a heterogeneous secretion profile of various cytokines during CAR T-cell therapy and confirmed a correlation between the cytokine secretion profile and the CAR T-cell cytotoxic activity. The capability to monitor immune cell cytokine secretion dynamics in a biomimetic tumor microenvironment could further help in study of cytokine release syndrome during CAR T-cell therapy and in development of more efficient and safer immunotherapies.

Sensitivity-enhanced nanoplasmonic biosensor using direct immobilization of two engineered nanobodies for SARS-CoV-2 spike receptor-binding domain detection

Sensitive, rapid, and easy-to-implement biosensors are critical in responding to highly contagious and fast-spreading severe acute respiratory syndrome coronavirus (SARS-CoV-2) mutations, enabling early infection screening for appropriate isolation and treatment measures to prevent the spread of the virus. Based on the sensing principle of localized surface plasmon resonance (LSPR) and nanobody immunological techniques, an enhanced sensitivity nanoplasmonic biosensor was developed to quantify the SARS-CoV-2 spike receptor-binding domain (RBD) in serum within 30 min. The lowest concentration in the linear range can be detected down to 0.01 ng/mL by direct immobilization of two engineered nanobodies. Both the sensor fabrication process and immune strategy are facile and inexpensive, with the potential for large-scale application. The designed nanoplasmonic biosensor achieved excellent specificity and sensitivity for SARS-CoV-2 spike RBD, providing a potential option for accurate early screening of the novel coronavirus disease 2019 (COVID-19).

Biomimetic nanoplasmonic sensor for rapid evaluation of neutralizing SARS-CoV-2 monoclonal antibodies as antiviral therapy

Monoclonal antibody (mAb) therapy is one of the most promising immunotherapies that have shown the potential to prevent or neutralize the effects of COVID-19 in patients at very early stages, with a few formulations recently approved by the European and American medicine agencies. However, a main bottleneck for their general implementation resides in the time-consuming, laborious, and highly-specialized techniques employed for the manufacturing and assessing of these therapies, excessively increasing their prices and delaying their administration to the patients. We propose a biomimetic nanoplasmonic biosensor as a novel analytical technique for the screening and evaluation of COVID-19 mAb therapies in a simpler, faster, and reliable manner. By creating an artificial cell membrane on the plasmonic sensor surface, our label-free sensing approach enables real-time monitoring of virus-cell interactions as well as direct analysis of antibody blocking effects in only 15 min assay time. We have achieved detection limits in the 102 TCID50/mL range for the study of SARS-CoV-2 viruses, which allows to perform neutralization assays by only employing a low-volume sample with common viral loads. We have demonstrated the accuracy of the biosensor for the evaluation of two different neutralizing antibodies targeting both Delta and Omicron variants of SARS-CoV-2, with half maximal inhibitory concentrations (IC50) determined in the ng/mL range. Our user-friendly and reliable technology could be employed in biomedical and pharmaceutical laboratories to accelerate, cheapen, and simplify the development of effective immunotherapies for COVID-19 and other serious infectious diseases or cancer.