More than 50 papers on surface plasmon resonance biosensors, published between 2016 and mid-2018, are reviewed. Papers concerning the determination of large particles such as vesicles, exosomes, cancer cells, living cells, stem cells, and microRNA are excluded, as these are covered by a very recent review. The reviewed papers are categorized into five groups, depending on the degree of maturity of the reported solution; ranging from simple marker detection to clinical application of a previously developed biosensor. Instrumental solutions and details of biosensor construction are analyzed, including the chips, receptors, and linkers used, as well as calibration strategies. Biosensors with a sandwich structure containing different nanoparticles are considered separately, as are SPR (Surface Plasmon Resonance) applications for investigating the interactions of biomolecules. An analysis is also made of the markers determined using the biosensors. In conclusion, there is shown to be a growing number of SPR applications in the solution of real clinical problems.

Human epididymis protein 4 (HE4) is an ovarian cancer marker. Various cut-off values of the marker in blood are recommended, depending on the method used for its determination. An alternative biosensor for HE4 determination in blood plasma has been developed. It consists of rabbit polyclonal antibody against HE4, covalently attached to a gold chip via cysteamine linker. The biosensor is used with the non-fluidic array SPRi technique. The linear range of the analytical signal response was found to be 2–120 pM, and the biosensor can be used for the determination of the HE4 marker in the plasma of both healthy subjects and ovarian cancer patients after suitable dilution with a PBS buffer. Precision (6–10%) and recovery (101.8–103.5%) were found to be acceptable, and the LOD was equal to 2 pM. The biosensor was validated by the parallel determination of a series of plasma samples from ovarian cancer patients using the Elecsys HE4 test and the developed biosensor, with a good agreement of the results (a Pearson coefficient of 0.989). An example of the diagnostic application of the developed biosensor is given—the influence of ovarian tumor resection on the level of HE4 in blood serum.

Interleukin-6 (IL-6) is a biomarker of inflammation, the advanced stage of COVID-19, and several cancers, including ovarian cancer. Two biosensors for the determination of IL-6 in blood plasma by array SPRi have been developed. One of these biosensors consists of the mouse monoclonal anti-IL-6 antibody as the receptor immobilized via the cysteamine linker. The second contains galiellalactone as the receptor, being an inhibitor specific for IL-6, immobilized via octadecanethiol (ODM) as the linker. Both biosensors are specific for IL-6. The biosensor with the antibody as the receptor gives a linear analytical response between 3 (LOQ) and 20 pg mL⁻¹ and has a precision between 8% and 9.8% and recovery between 97% and 107%, depending on the IL-6 concentration. The biosensor with galiellalactone as the receptor gives a linear analytical response between 1.1 (LOQ) and 20 pg mL⁻¹, and has a precision between 3.5% and 9.3% and recovery between 101% and 105%, depending on IL-6 concentration. Both biosensors were validated. Changes in IL-6 concentration in blood plasma before and after resection of ovarian tumor and endometrial cyst, as determined by the two developed biosensors, are given as an example of a real clinical application.