Aptamer versus Antibody Recognition Elements in Electrochemical Biosensors for Breast Cancer Biomarkers: A Comparative Systematic Review and Quantitative Meta-AnalysisFirst
Jul 2026· International Journal For Multidisciplinary Research· Vol 8· 0 citations· 15 references
TL;DR
This review highlights the comparison of two electrochemical platforms—antibody-based platform (immunosensor) and aptamer-based platform (aptasensor)—developed from 2021 to 2026 for four important BC biomarkers, human epidermal growth factor receptor 2 (HER2), carbohydrate antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), and circulating microRNA-21.
Abstract
Accurate diagnosis of biomarkers of breast cancer (BC) at an early stage is at the centre of the reduction in breast cancer (BC) mortality. In order to provide an alternative, low cost, compact and fast measurement methods to traditional immunoassays and imaging techniques, electrochemical biosensors are now being developed, controlling the analytical performance of the biosensors by choosing the appropriate biorecognition element. This review highlights the comparison of two electrochemical platforms—antibody-based platform (immunosensor) and aptamer-based platform (aptasensor)—developed from 2021 to 2026 for four important BC biomarkers, human epidermal growth factor receptor 2 (HER2), carbohydrate antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), and circulating microRNA-21. The limits of detection (LOD), linear range, stability and reproducibility data reported in the literature were reviewed and combined quantitatively, and presented with qualitative consensus scoring for production cost, batch reproducibility and clinical maturity. In general, aptamer-based platforms have an advantage in terms of their chemical stability and low batch-to-batch variability, as antibody-based platforms have an advantage in terms of their analytical maturity and availability, and the analytical level appears to be more dependent on the nanomaterial signal- amplification strategy than on only the recognition-element class. The heterogeneous nature of the validation methods used in different studies makes statistical comparison of studies difficult, and is one of the main translational barriers.
Triple-negative breast cancer (TNBC) is when the patient does not have the three most targeted molecules (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 or HER2) and the patient resorts to chemotherapy (cytotoxic), and poor prognosis due to the fact that the three most targeted molecules are the ones that are monitored. There has been growing interest in the measurement of alternative circulating markers e.g. epidermal growth factor receptor (EGFR), soluble programmed death-ligand 1 (sPD-L1), exosomal PD-L1, CD44, mucin-1, tumour-derived microRNAs (miR-10b, miR-21, miR-652), and circulating tumour cells (CTCs) that do not require repeated tissue biopsies. Label-free electrochemical biosensors that can detect a binding event as a change in charge-transfer resistance, capacitance or redox current instead of a secondary enzymatic or fluorescent reporter provide a means of fast, inexpensive, and perhaps point-of-care measurement of these markers. In this review, the recognition strategies that have been used to impart selectivity to these platforms (antibodies, aptamers, molecularly imprinted polymers, peptides and nucleic-acid probes) and the nanomaterial transducers (graphene and its derivatives, 2D MXenes, metal and bimetallic nanoparticles, metal/covalent-organic frameworks) that have been used to amplify the signal generated by these platforms are reviewed. The platforms used to detect HER2, EGFR, PD-L1, CD44 and TNBC-specific miRs that were representative in the last 5 years are compared and the special lack of TNBC-specific multi-marker, clinically validated devices is highlighted. The review ends with a discussion of issues that present practical problems to address, namely sample-matrix fouling, recognition-layer stability, reproducibility/regulatory validation between the lab-scale sensors and the deployable point-of-care biosensors and diagnostics, and prioritizes the multiplexed clinically translatable TNBC biosensing.
T L Manasa, Rajesh Kumar Upadhyay, Divyashree H B· International journal of com...· 0 citations
Breast cancer is the most prevalent cancer among women in the world and early diagnosis of cancer is the most important predictor of long-term survival. While currently popular screening tests such as mammograms and confirmatory tissue biopsies have drawbacks such as invasiveness, expense and less sensitivity in dense breast tissue, there has been a growing interest in minimally invasive molecular liquid-biopsy biomarkers. Among the analytes, miRNAs (in particular miR-21 and miR-155) and tumour derived exosomes are promising analytes because of their tight mechanistic relation to the oncosignalling pathways and/or their stability in biofluids. Alternatively, using a label free electrochemical biosensor in which the change of electron transfer at the interfaces is detected by the addition of the target molecule, can also be rapid, cost efficient and very sensitive for a fluorescence or enzyme linked assay. Systematic review and meta-analysis of the label-free electrochemical biosensing platforms used to detect miR-21, miR-155 and exosomes in the context of breast cancer diagnosis and prognosis are presented for the period 2021-2026. According to PRISMA guidelines, twenty primary studies were found from PubMed, ScienceDirect, Scopus, and Web of Science and were assessed for their sensor architecture and nanomaterial transducer, recognition element, limit of detection, linear dynamic range and clinical validation. The pooled estimates from the eleven diagnostic accuracy studies are 90% (0.88–93%) for the sensitivity and 92% (87–95%) for the specificity, and the summary area-under-curve is 0.94 (0.86–0.98). These application areas, such as electrode nanoarchitecture, aptamer/PNA probe design and CRISPR-assisted signal amplification, become the key areas of diagnostic performance, whereas reproducibility, interference with the biological matrix, and limited clinical-cohort validation appear to be the major barriers to bring laboratory prototypes to the point-of-car.
Manasa T L, R. Upadhyay, D. H B· International Journal For Mu...· 0 citations
Tumor markers are critical for early cancer diagnosis and directly influence treatment outcomes and patient survival. Although enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) show satisfactory selectivity in clinical applications, their limited sensitivity for low-abundance biomarkers, relatively long assay time, and reproducibility issues have promoted the development of advanced immunosensing platforms. Recent progress in nanomaterial synthesis has improved immunosensor performance by enhancing antibody immobilization, electron transfer, catalytic activity, signal amplification, photoelectric conversion, and luminescence efficiency. This review summarizes nanomaterial-enhanced immunosensors for clinically relevant tumor biomarkers, including carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), cancer antigen 153 (CA153), alpha-fetoprotein (AFP), cancer antigen 125 (CA125), cancer antigen 199 (CA199), and human epidermal growth factor receptor 2 (HER2). To reduce repetition and emphasize analytical performance rather than nominal material categories, this review adopts a platform-centered and mechanism-oriented framework. Electrochemical, photoelectrochemical, electrochemiluminescent, and chemiluminescent immunosensors are compared as major signal transduction platforms, with representative nanomaterials discussed according to their roles in antibody immobilization, electron-transfer acceleration, catalytic amplification, charge separation, luminescence regulation, magnetic enrichment, and interface stabilization. In addition, cross-platform comparisons of sensitivity, detection limit, specificity, recovery, assay time, storage stability, cost, scalability, and clinical applicability are provided to clarify the translational value of different sensing strategies. This comparative analysis highlights that clinical applicability is primarily determined by integrated platform performance, including sensitivity, stability, manufacturability, and compatibility with point-of-care testing, rather than by the use of a specific nanomaterial alone.
Shengbo Jin, Jun Yu, Yuxin Jiang et al.· Frontiers in Chemistry· 0 citations
Breast cancer is one of the most prevalent cancers worldwide and a leading cause of cancer-related mortality. However, early detection of the disease can significantly reduce the mortality rate of cancer patients. The current detection methods of breast cancer are expensive, time consuming, invasive and require professional assistance. To overcome these challenges, a minimally invasive low-cost paper-based point-of-care (POC) electrochemical sensing platform has been developed for early-stage detection of breast cancer. The proposed sensor is fabricated using a screen-printing technique, incorporating two-dimensional Ti3C2 (MXene) nanosheets onto the working electrode. These nanosheets provide enhanced electrochemical performance, enabling an exceptionally low limit of detection (LOD) ∼ 4 cells mL-1) attributed to their high conductivity and large surface area. The electrode surface is further functionalized with specific aptamers, facilitating selective target recognition. The proof-of-concept study was validated using multiple cell lines, including A549 (lung cancer cells), NIH3T3 (fibroblast), and HEK293 (kidney cells), and MDA-MB-231(breast cancer cell line), to evaluate the specificity of the developed aptasensor. The sensing mechanism relies on the selective binding of aptamers to Mammaglobin A proteins expressed on circulating tumor cells (CTCs). This interaction induces conformational changes in the aptamer, resulting in measurable alterations in the electrochemical properties at the electrode interface. The conjugation of the biomarker with the aptamer upon aptamer-protein interaction, results in a change in current, which is sensed by cyclic voltammogram (CV). The resulting signal is used to plot a calibration curve for quantitative analysis. Further, these sensing experiments are validated using in vitro experiments with human blood serum as a proof of concept. Overall, the developed paper-based electrochemical POC device offers significant advantages, including affordability, ease of use, rapid response, and quantitative detection capability.
Jaydeep Kanungo, Somya Sadaf, D. Sharma et al.· Talanta: The International J...· 0 citations
Nowadays, cancer has become one of the major causes of mortality all over the world, irrespective of age and gender. The early detection of cancer can markedly enhance patient survival outcomes. Cancer cells are analyzed by comparing the optimum concentration of different types of biomarkers, including alpha-fetoprotein (AFP), prostate-specific antigen (PSA), microRNA-21, and carcinoembryonic antigen (CEA), in biological samples. These biomarkers play a crucial role in the early detection, screening and treatment of cancer. Novel colorimetric assays based on modified AuNPs are discussed in this review, which have opened a new avenue for the facile, point-of-care diagnosis of cancer. Due to their unique characteristics such as surface plasmon resonance (SPR), AuNPs provide a selective, trustworthy and simple strategy to detect cancerous cells by visualizing a color change when used in colorimetry. The principles of the sensing methods (aggregation, anti-aggregation, etching, and enzyme-mimetic activity) are illustrated in this review. Besides, some portable devices, such as paper-based devices (PADs), barcodes, and lateral flow assays (LFTs), are mentioned, which have made this complicated detection process as convenient as a pregnancy strip test. However, these devices are primarily limited by their low sensitivity and inadequate capability for accurate quantitative analysis. This review highlights the progress of paper-based colorimetric sensing devices for the detection of cancers, such as breast cancer, prostate cancer, pancreatic cancer, and bladder cancer. Furthermore, we outline the key advantages of these devices and emphasize their major limitations. Finally, we have also mentioned some perspectives that may improve the sensitivity of these colorimetric devices as biosensors.
Abstract Early detection of breast cancer is crucial for improving women’s health and survival rates. However, traditional diagnostic and treatment approaches are often expensive, time-intensive, complex, and may lack the sensitivity and specificity needed for effective clinical use. Detecting early-stage cancer and monitoring recurrence demand highly sensitive, reproducible detection of low-abundance biomarkers. Electrochemical biosensors offer a promising solution, enabling rapid, cost-effective diagnostics suitable for point-of-care (POC) applications. Among these, carbon-based nanomaterials, such as: carbon nanotubes (CNTs), graphene, graphene oxide (GO), reduced graphene oxide (rGO), carbon dots (CDs), and their nanocomposites, stand out for their unique properties that support the sensitive detection of breast cancer biomarkers. This review comprehensively explores recent advancements (2020 to March 2025) in using carbon-based materials for POC electrochemical sensors in breast cancer diagnostics. It covers synthesis methods, structural characteristics, and detection mechanisms associated with key biomarkers, like: HER2, CA 15–3, CEA, CA 125, BRCA1, and MUC1, including performance metrics such as linear range, limit of detection (LOD), and sensitivity. Additionally, the potential integration of these biosensors with smartphones is discussed, along with an overview of sustainability challenges and future research directions in this field. Graphical AbstractDiagram of an electrochemical biosensor for breast cancer detection, showing components, smartphone integration, and future tech directions.This comprehensive diagram illustrates an electrochemical biosensor for breast cancer detection. The left panel highlights the issue with a human silhouette and a bar graph projecting global breast cancer statistics by 2045, listing markers like CA 125. The center details the biosensor's construction, including bioreceptors and a transducer made from carbon-based nanomaterials. The right side shows a smartphone displaying CA125 detection results at 1.54 U/mL, emphasizing features such as rapid, portable diagnosis. Lastly, future directions include AI and wearable sensors, enhancing digital health integration.
Mohsen Ahmadipour, Anish Bhattacharya, Masoud Ahmadipour et al.· Critical Reviews in Biotechn...· 0 citations