High-Sensitivity Detection of the Lung Cancer Biomarker CYFRA21-1 in Serum Samples Using a Carboxyl-MoS2 Functional Film for SPR-Based Immunosensors

Abstract

We constructed a novel surface plasmon resonance (SPR) detection assay using carboxyl-functionalized molybdenum disulfide (carboxyl-MoS 2) nanocomposites as a signal amplification sensing film for the ultrasensitive detection of the lung cancer-associated biomarker cytokeratin 19 fragment (CYFRA21-1). The experiment succeeded in MoS 2 reacted with chloroacetic acid giving carboxyl-MoS 2 as the reaction product. The additional shoulder in the C 1s and O 1s peaks of carboxyl-MoS 2 , which were increased in X-ray photoelectron spectroscopy, confirmed the presence of O-C=O groups on the surface of the carboxyl-MoS 2. Compared to MoS 2 , the experimental results confirmed that carboxyl-modified MoS 2 had improved low impedance and low refractive index. The carboxyl-MoS 2-based chip had a high affinity, with an SPR angle shift enhanced by 2.6-fold and affinity binding K A enhanced by 15-fold compared to a traditional SPR sensor. The results revealed that the carboxyl-MoS 2-based chip had high sensitivity, specificity, and SPR signal affinity, while the CYFRA21-1 assay in spiked clinical serum showed a lower detection limit of 0.05 pg/mL and a wider quantitation range (0.05 pg/mL to 100 ng/mL). The carboxyl-MoS 2-based chip detection value was about 10 4 times more sensitive than the limit of detection of an enzyme-linked immunosorbent assay (ELISA) (0.60 ng/mL). The results showed that the carboxyl-MoS 2-based chip had the potential to rapidly assay complex samples including bodily fluids, whole blood, serum, plasma, urine, and saliva in SPR-based immunosensors to diagnose diseases including cancer.

Exploring Graphene and MoS2 Chips Based Surface Plasmon Resonance Biosensors for Diagnostic Applications

“…Based on Figure 15B , biosensor selectivity also shows good results. The SPR angle shift on the CYFRA21-1 protein shows a much greater magnitude than other types of proteins (CA-199, hCG, PAPP-A, PAPP-A2, and HAS) (Chiu and Yang, 2020 ).…”

“…Chiu and Yang ( 2020 ) used a single-layer MoS 2 -COOH for signal amplification to detect lung cancer associated with the cytokeratin 19 fragment biomarker (CYFRA21-1) using an SPR-based biosensor. To detect CYFRA21-1, MoS 2 /COOH-based SPR chip was functionalized using lung cancer antibodies (anti-CYFRA21-1, TROMA-III).…”

“…(B) Sensor selectivity for different types of proteins. Figures (A,B) were reproduced from (Chiu and Yang, 2020 ) with permission from Frontiers.…”

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

“…This nanomaterial has been recently used in several SPR-based approaches [ 104 ]. SPR immunosensors were developed for the detection of biomarker proteins using both direct immobilization [ 105 ], coupling via terminal -COOH groups introduced through sulphur vacancies [ 106 ], and the decoration of nanomaterial deposited in the form of nanoflowers on the surface of the SPR transducer with gold nanoparticles [ 107 ].…”

Low-Fouling Substrates for Plasmonic Sensing of Circulating Biomarkers in Biological Fluids

“…Several examples involving the detection of alpha fetoprotein hepatocellular cancer biomarker and the CA125/MUC16 ovarian tumor circulating biomarker have employed SERS, SPR and SPRi applications without exploiting any other antifouling strategy besides the dilution of serum samples [75][76][77]. In this line, an SPR-based immunosensor makes use of carboxyl-modified MoS 2 composites to detect the lung-cancer-associated biomarker cytokeratin 19 fragment (CYFRA21-1) in spiked diluted samples [78]. The fouling effect was measured by evaluating SPR angular shifts for various serum dilutions.…”