Sensitive Dual-Mode Biosensors for CYFRA21-1 Assay Based on the Dual-Signaling Electrochemical Ratiometric Strategy and “On–Off–On” PEC Method

Abstract

Herein, an electrochemical (EC)–photoelectrochemical (PEC) dual-mode biosensor was constructed for cytokeratin 19 fragment 21-1 (CYFRA21-1) assay based on the dual-signaling electrochemical ratiometric strategy and “on–off–on” PEC method. The indium tin oxide (ITO) electrode was modified by 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA)@C60 and gold nanoparticles (Au NPs), and the double-stranded DNA composed of thiol/methylene blue (MB)-labeled single-stranded DNA (ssDNA) (S0-MB) and antibody/ferrocene (Fc)-labeled ssDNA (Ab1-S1-Fc) was immobilized on the Au NPs/PTCDA@C60/ITO electrode via the Au–S bond between Au NPs and thiol of S0-MB. With the help of another antibody-labeled ssDNA (Ab2-S2), the presence of CYFRA21-1 triggered a typical antigen–antibody sandwich immune reaction (Ab1, CYFRA21-1, and Ab2) and proximity hybridization between Ab1-S1-Fc and Ab2-S2. This caused the release of Ab1-S1-Fc from the modified electrode and the change of S0-MB to a hairpin structure, resulting in a decrease (an increase) of the oxidation peak current of Fc (MB) and an increase of the photocurrent due to the enhancing (inhibiting) effect of MB (Fc) on the photoelectric performance of the Au NPs/PTCDA@C60/ITO electrode. Thus, CYFRA21-1 was detected by the developed EC–PEC dual-mode sensing platform sensitively, and the linear response ranges of 0.001–40 ng/mL with a detection limit of 0.3 pg/mL for the EC technique and 0.0001–4 ng/mL with a detection limit of 0.03 pg/mL for the PEC method were obtained. Furthermore, by changing the specific antibodies of disease-related biomarkers, the developed dual-mode biosensing platform could be readily extended to detect other antigens, implying its great potential applications in biological analysis and early disease diagnosis.

Nucleic acid isothermal amplification-based soft nanoarchitectonics as an emerging electrochemical biosensing platform

“…This is advantageous when compared to the above-mentioned ratiometric strategies that also showed two readouts, however, the two readouts are from the same detecting method. For example, electrochemical/ECL dual- mode, 138,139 electrochemical/photoelectrochemical (PET) dualmode, 140,141 and ECL/PET dual-mode 142 sensing strategies have been reported for improved cross-validating detection. Zhou et al combined the electrochemistry method and surface-enhanced Raman scattering (SERS) technology to realize a dual-mode assay for miRNA.…”

MOF@COF Heterostructure Hybrid for Dual-Mode Photoelectrochemical–Electrochemical HIV-1 DNA Sensing

“…Apart from PEC biosensors, electrochemical (EC) ones have also been explored for sensitively detecting HIV-1 , in light of their features such as high sensitivity, simple detection instrument and data analysis, and small dosage of samples . Consequently, by integrating the advantages of PEC and EC techniques, the dual-mode PEC–EC detection approach is expected to be a promising method for efficiently analyzing targets, such as H 2 S, bovine hemoglobin, cytokeratin 19 fragment 21-1, and miRNA-141 . Since advanced nanomaterials with high photoactivity and outstanding electrochemical conductivity are fairly scarce, the advancement for the dual-mode PEC–EC sensing technique is greatly hampered.…”

Upconversion Nanoparticles Assembled with Gold Nanourchins as Luminescence and Surface-Enhanced Raman Scattering Dual-Mode Aptasensors for Detection of Ochratoxin A

“…However, most of the abovementioned methods are based on a single mode. Quantitative determination relying on single-mode readout is easily interfered with by the complicated experimental conditions, such as coexisting interferents, different operators, equipment, and nonstandard assay procedures . Over the years, considerable attention has been paid to dual-mode sensors.…”