Recent Advancements in Receptor Layer Engineering for Applications in SPR-Based Immunodiagnostics

Abstract

The rapid progress in the development of surface plasmon resonance-based immunosensing platforms offers wide application possibilities in medical diagnostics as a label-free alternative to enzyme immunoassays. The early diagnosis of diseases or metabolic changes through the detection of biomarkers in body fluids requires methods characterized by a very good sensitivity and selectivity. In the case of the SPR technique, as well as other surface-sensitive detection strategies, the quality of the transducer-immunoreceptor interphase is crucial for maintaining the analytical reliability of an assay. In this work, an overview of general approaches to the design of functional SPR-immunoassays is presented. It covers both immunosensors, the design of which utilizes well-known and often commercially available substrates, as well as the latest solutions developed in-house. Various approaches employing chemical and passive binding, affinity-based antibody immobilization, and the introduction of nanomaterial-based surfaces are discussed. The essence of their influence on the improvement of the main analytical parameters of a given immunosensor is explained. Particular attention is paid to solutions compatible with the latest trends in the development of label-free immunosensors, such as platforms dedicated to real-time monitoring in a quasi-continuous mode, the use of in situ-generated receptor layers (elimination of the regeneration step), and biosensors using recombinant and labelled protein receptors.

Highly sensitive and selective surface plasmon resonance biosensor for the detection of SARS-CoV-2 spike S1 protein

“…Surface plasmon resonance (SPR) technology possesses the advantages of fast response, not needing labeling of the analyte, real-time qualitative and quantitative analysis, and providing reactant molecular bonding information, thus exhibiting great potential in clinical applications. [14][15][16][17][18] However, the inability of traditional SPR sensing technology to detect trace targets in complex matrices limits its practical application. The growing use of nanomaterials in fabricating SPR sensor chips and response signal enhancers is promising for SPR sensing.…”

Sensitivity Analysis of Single- and Bimetallic Surface Plasmon Resonance Biosensors

“…The interaction between the immobilized bioreceptor and captured analyte particles modifies SPR conditions, which, in turn, generate a change of the sensor’s reflectance, which can be measured and correlated with the change of the analyte’s concentration. SPR biosensors have found applications in many fields, including in environmental protection [ 3 , 4 , 5 , 6 , 7 , 8 ], biological testing [ 9 , 10 , 11 , 12 , 13 , 14 ], food safety [ 15 , 16 , 17 , 18 , 19 , 20 ], and clinical diagnostics [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Application of Nanopore Sensors for Biomolecular Interactions and Drug Discovery

“…[26][27][28] For example, they can reveal conformational changes and individual mechanistic steps derived from the interaction between molecules, which might be buried in ensemble data [22] In addition to the limitations of ensemble averaging-based classical approaches, surface plasma resonance (SPR) has also suffered from low sensitivity. [29] Moreover, insufficient rejection of non-specific binding upon the immunosensing layer reduces the sensitivity and selectivity of SPR. Consequently, there is an increment of false positive and false negative results, resulting in a failure of validation.…”

“…Nanopore technologies have the potential to reveal the characteristics of a single target molecule that is not accessible to current ensemble methods, and demonstrate high sensitivity and specificity in utilizing the probe conjugated to the nanopore, [6b,22] or protein adaptor within the nanopore [26–28] . For example, they can reveal conformational changes and individual mechanistic steps derived from the interaction between molecules, which might be buried in ensemble data [22] In addition to the limitations of ensemble averaging‐based classical approaches, surface plasma resonance (SPR) has also suffered from low sensitivity [29] . Moreover, insufficient rejection of non‐specific binding upon the immunosensing layer reduces the sensitivity and selectivity of SPR.…”