SERS biosensor with plastic antibodies for detection of a cancer biomarker protein.

Surface-enhanced Raman scattering (SERS) is a powerful method for detecting breast cancer-specific biomarkers due to its extraordinary enhancement effects obtained by localized surface plasmon resonance (LSPR) in metallic nanostructures at hotspots. In this research, gold nanostars (AuNSs) were used as SERS probes to detect a cancer biomarker at very low concentrations. To this end, we combined molecularly imprinted polymers (MIPs) as a detection layer with SERS for the detection of the biomarker CA 15-3 in point-of-care (PoC) analysis. This required two main steps: (i) the deposition of MIPs on a gold electrode, followed by a second step (ii) antibody binding with AuNSs containing a suitable Raman reporter to enhance Raman signaling (SERS). The MPan sensor was prepared by electropolymerization of the monomer aniline in the presence of CA 15-3. The template molecule was then extracted from the polymer using sodium dodecyl sulfate (SDS). In parallel, a control material was prepared in the absence of the protein (NPan). Surface modification for the control was performed using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the sensor was evaluated using the SERS technique, in which the MPan sensor is first incubated with the protein and then exposed to the SERS probe. Under optimized conditions, the device showed a linear response to CA 15-3 concentrations from 0.016 to 248.51 U mL-1 in a PBS buffer at pH 7.4 in 1000-fold diluted serum. Overall, this approach demonstrates the potential of SERS as an optical reader and opens a new avenue for biosensing applications.

Colorimetric Paper-Based Sensors against Cancer Biomarkers.

Cancer is a major cause of mortality and morbidity worldwide. Detection and quantification of cancer biomarkers plays a critical role in cancer early diagnosis, screening, and treatment. Clinicians, particularly in developing countries, deal with high costs and limited resources for diagnostic systems. Using low-cost substrates to develop sensor devices could be very helpful. The interest in paper-based sensors with colorimetric detection increased exponentially in the last decade as they meet the criteria for point-of-care (PoC) devices. Cellulose and different nanomaterials have been used as substrate and colorimetric probes, respectively, for these types of devices in their different designs as spot tests, lateral-flow assays, dipsticks, and microfluidic paper-based devices (µPADs), offering low-cost and disposable devices. However, the main challenge with these devices is their low sensitivity and lack of efficiency in performing quantitative measurements. This review includes an overview of the use of paper for the development of sensing devices focusing on colorimetric detection and their application to cancer biomarkers. We highlight recent works reporting the use of paper in the development of colorimetric sensors for cancer biomarkers, such as proteins, nucleic acids, and others. Finally, we discuss the main advantages of these types of devices and highlight their major pitfalls.

Dual biorecognition by combining molecularly-imprinted polymer and antibody in SERS detection. Application to carcinoembryonic antigen.

This work reports the innovative combination of a molecularly-imprinted polymer (MIP) and a natural antibody for the accurate surface-enhanced Raman spectroscopy (SERS) detection of carcinoembryonic antigen (CEA). The MIP material acted as a pre-concentration scheme for the target protein, while the natural antibody was responsible to signal the presence of CEA on the MIP platform. Gold-based screen-printed electrodes were used as substrate and gallic acid (GA) was used herein for the first time in the assembly of a MIP film, by electropolymerization, in the presence of CEA. This layer was further covered by a second ultra-thin film of electropolymerized benzoic acid (BA), to avoid non-specific binding. The rebinding features of the MIP film were evaluated by electrochemical impedance spectroscopy (EIS) and a linear response was observed from 1 to 1000 ng/mL. For a sensitive SERS detection, the MIP film was first incubated in sample containing CEA and next incubated in SERS tag. For the SERS tag, gold nanostars (AuNSs) were employed as metal support, coupled to 4-aminothiophenol (4-ATP) as Raman reporter and to a natural antibody for CEA as recognition element. The overall system showed a sensitive response down to 1.0 ng/mL, which was different from the blank signal. Overall, the innovative approach presented herein combines the advantages of using two different targeting elements for CEA. The costs and time of MIP production were substantially low due to selection of electropolymerization approach and the proposal described herein may be extended to other target molecules.