Optical fiber biosensors reach attomolar cancer biomarker detection in lab tests

Optical fiber biosensors can now detect cancer biomarkers at concentrations as low as femtomolar to attomolar levels, according to a systematic review published on 6 July 2026 in the journal Biosensors and Biomolecular Electronics. The review, led by Muhammad Moazzam and Anum Afroz, followed the PRISMA 2020 guidelines and analyzed 25 relevant studies published between 2016 and 2026, drawn from PubMed, Scopus, Web of Science, IEEE Xplore, ScienceDirect, and Google Scholar.

The studies covered multiple cancer types, including breast, lung, prostate, thyroid, ovarian, and colorectal cancers, and targeted biomarkers such as HER2, CEA, PSA, CD44, miRNA-21, and CA125. The biosensor platforms examined included surface plasmon resonance (SPR)-based sensors, tilted fiber Bragg gratings (TFBGs), Fabry–Perot interferometers, microfiber couplers, and nanomaterial-enhanced sensors. Despite the impressive analytical performance, the authors conclude that most of these devices remain proof-of-concept systems that have not been widely clinically validated, relying largely on buffer solutions or spiked bio-samples rather than real patient specimens.

The motivation behind the review is grounded in a persistent clinical problem. Cancer remains a major cause of death worldwide, in part because it is often diagnosed late and conventional diagnostic tools such as blood tests are not sensitive enough for early detection. In 2022, around 20 million new cancer cases were detected alongside 9.7 million cancer-related deaths. Traditional biomarker detection methods, including enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), fluorescence assays, western blot, and electrochemical assays, are cost-intensive, involve long processing times, are labor-intensive, and require centralized laboratory infrastructure, which limits their use for rapid point-of-care diagnostics.

Optical fiber biosensors offer a different approach. In these systems, optical fibers serve both as light guides and as sensing interfaces. When a functionalized sensing surface encounters a target biomarker, the binding event produces measurable optical responses, including wavelength shifts, refractive index changes, interferometric modulation, and variations in surface plasmon resonance. The technology’s key advantages include miniaturization, high sensitivity, real-time monitoring capability, biocompatibility, low sample volume requirements, flexibility, and resistance to electromagnetic interference. These properties make optical fibers attractive platforms for detecting the faint molecular signals that cancers shed into blood and other body fluids.

The review found that breast cancer was the most-studied disease, with at least seven studies examining the detection of HER2, the primary molecular biomarker for this cancer type. Prostate cancer was the next most-studied, with at least three studies focused on PSA and miRNA-21. Carcinoembryonic antigen (CEA), a pan-cancer biomarker, was also widely investigated, with TFBG-SPR probes, Fabry–Perot interferometers, and microfiber couplers all evaluated for its detection. Lung cancer studies focused on CK17, neuron-specific enolase, and DNA-associated markers, while other reported targets included CD44, CA125, thyroglobulin, CEACAM5, and CCL5.

Some of the most striking performance figures came from the most advanced platforms. A hetero-core SPR sensor achieved a human serum limit of detection of 1.86 × 10−19 M for miRNA-21, one of the few studies with clinically relevant validation in a real biological matrix. A Fabry–Perot interferometric system detected CCL5 in serum at 17.6 attomolar, and a TFBG-SPR probe reached a detection limit of 0.07 femtomolar for CEA in a controlled laboratory setting. A localized surface plasmon resonance-based sensor achieved a detection limit of 93.11 fg/mL for thyroglobulin. By contrast, microfiber-based sensors generally achieved detection limits in the picomolar to femtomolar range, though they offer benefits of easier fabrication, lower cost, miniaturization, and reduced sample volume.

The dramatic sensitivity gains of recent years are closely tied to the integration of nanomaterials. Gold nanoparticles, black phosphorus nanosheets, MoSe2 nanosheets, graphene derivatives, and polymer-based nanostructures have all been used to enhance biomolecular interaction and signal amplification. These materials improve refractive index modulation and binding sensitivity, enabling the ultra-low detection limits reported in the newest studies. The review also documented a clear technological trajectory: earlier research reported detection limits in the nanogram-per-milliliter and picomolar range, while more recent work has pushed into the femtomolar and attomolar range, alongside a general shift from labeled detection methods toward real-time, label-free monitoring, particularly in papers published from 2020 onwards.

Biorecognition strategies have also evolved. Most studies used antibody-based recognition systems, typically deposited on fiber surfaces through silanization chemistry using APTES or APTMS and then covalently coupled with EDC/NHS crosslinking. Aptamer-based recognition systems were reported as well, especially for HER2 detection, where aptamers offer greater stability, lower cost, and easier chemical modification than antibodies. Molecularly imprinted polymers have also been demonstrated as robust, reusable, and cost-effective recognition elements. Signal transduction in most of the selected biosensors relied on resonance wavelength shifts, interferometric spectral modulation, displacement of the SPR dip, or optical intensity changes, all linked to refractive index changes at the sensing interface when antigen binds to its bioreceptor.

However, the review’s central message is one of caution. Although analytical performance was strong, most studies were not clinically validated. The majority of experiments were carried out in buffer solutions or spiked serum samples, and only a small number utilized clinical samples such as human serum, plasma, or biopsy tissues. Among the more convincing translation efforts, Wei and colleagues showed good correlation between an optical microfiber coupler biosensor approach and standard chemiluminescence assays for CEA detection. The authors also noted that reproducibility assessment was frequently underreported or limited to qualitative descriptions, that standardized performance metrics such as sensitivity, specificity, and area under the curve were often absent, and that biofouling, non-specific binding in complex biological matrices, and environmental sensitivity remain common challenges. The complexity and scalability of fabricating nanostructured optical fiber platforms further hinder clinical translation, and direct comparisons with established methods such as ELISA or PCR were not found in the reviewed literature.

The authors argue that standardized validation procedures, multicenter clinical trials, scalable manufacturing techniques, and integration with point-of-care diagnostic platforms will be needed to move the field forward. They also acknowledge limitations of their own review, including possible publication bias favoring studies that report high sensitivity and successful outcomes, and the impossibility of formal meta-analysis given the wide variation in sensor design, biomarker type, sample matrix, and reporting standards. A qualitative comparative synthesis was performed instead. Looking ahead, the review identifies liquid biopsy as a particularly promising application area, with next-generation biomarkers such as circulating nucleic acids and extracellular vesicles increasingly emerging alongside conventional protein markers. Future research, the authors suggest, should emphasize extensive clinical validation, sensor robustness, and the integration of biosensors with microfluidics and artificial intelligence systems to bridge the gap between laboratory innovation and clinical care.

Subject of Research: A systematic review of optical fiber biosensors for detecting cancer biomarkers

Article Title: Optical fiber biosensors for cancer biomarker detection—a review

Article References: Moazzam, M., & Afroz, A. (2026). Optical fiber biosensors for cancer biomarker detection—a review. Biosensors and Biomolecular Electronics, 1(1), Article 8. https://doi.org/10.1186/s44510-026-00008-1

Image Credits: AI Generated

DOI: 10.1186/s44510-026-00008-1

Keywords: optical fiber biosensors, cancer biomarkers, systematic review, surface plasmon resonance, liquid biopsy, HER2, CEA, miRNA-21, nanomaterials, limit of detection, early cancer detection, Fabry-Perot interferometer