The study presents a new membrane-based sensing platform that selectively detects the cancer biomarker carbohydrate antigen 19-9 (CA 19-9) using a visible fluorescence color change under UV light.
Pancreatic cancer remains one of the deadliest malignancies, making early detection critical. CA 19-9, a high-molecular-weight glycoprotein (~210 kDa), is widely used in clinical practice for prognosis and treatment monitoring, with serum levels above 37 U mL-1 associated with disease progression.
Current CA 19-9 detection methods, including enzyme-linked immunosorbent assays and electrochemical sensors, are sensitive but usually require expensive instrumentation and trained personnel.
These constraints limit their suitability for rapid or decentralized testing.
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Molecular Imprinting and Ratiometric Fluorescence
To address this, the researchers investigated molecularly imprinted polymers (MIPs), synthetic materials engineered with binding cavities that mimic biological recognition sites.
MIPs offer high chemical stability and selectivity, making them attractive alternatives to antibodies in sensing applications.
The team integrated MIPs with a ratiometric fluorescence strategy to improve robustness against background interference. Yellow-emitting quantum dots (y-QDs) were embedded as target-responsive probes, while blue-emitting carbon dots (b-CDs) served as a stable internal reference.
As only the y-QDs are quenched when CA 19-9 binds to the imprinted cavities, the ratio between blue and yellow emission provides a reliable readout independent of absolute signal intensity.
A Dual-Emission Membrane Sensor
Using a surface imprinting approach, CA 19-9 was employed as a molecular template during polymerization and later removed to create selective recognition sites.
The resulting dual-emission molecularly imprinted polymers were immobilized onto porous polyamide membranes, producing dual@MIPs@mbr.
When exposed to increasing concentrations of CA 19-9, the membranes exhibited a visible fluorescence shift from yellow-green to blue under controlled 365 nm UV illumination.
This color change enabled both visual and quantitative detection without the need for spectrometers or external calibration beyond a fixed UV source.
Analytical Performance, Selectivity, and Stability
The membranes demonstrated a linear response to CA 19-9 across a concentration range of 4.0 to 400 U mL-1, with a limit of detection of 0.056 U mL-1 in diluted serum.
High selectivity was observed against common serum interferents, with ratiometric changes driven by specific antigen–cavity interactions rather than nonspecific adsorption.
All measurements were conducted in 1 % diluted human serum to prevent nonspecific fluorescence quenching.
As a result, measured concentrations correspond to higher CA 19-9 levels in undiluted samples, aligning the analytical range with clinically relevant thresholds.
Short-term stability tests showed that the membranes maintained reliable performance for several days under dry storage, consistent with their intended use as disposable sensing elements.
Recovery studies showed good reproducibility at clinically relevant concentrations, although reduced recovery was observed at very high CA 19-9 levels, possibly due to partial saturation of imprinted binding sites.
However, the system has not yet been evaluated using real clinical samples. The authors emphasize that the current work establishes analytical feasibility rather than a validated diagnostic tool.
MIP Sensors Show Potential, But Aren't Ready Yet
The study demonstrates that combining molecular imprinting with dual-emission fluorescence can yield a selective and visually interpretable sensing platform suitable for low-cost, point-of-care applications.
By avoiding biological receptors and complex instrumentation, the approach offers a promising route toward portable cancer biomarker detection.
Further validation using patient samples will be required to assess diagnostic performance and clinical use, but the work provides a clear foundation for future development of instrument-free biosensing technologies.
Journal Reference
Rodrigues, E. et al. (2025). Molecularly Imprinted Membranes: Dual@ MIPs@ mbr for On-Site Detection of CA 19-9. Sensors, 25(23), 7363. DOI: 10.3390/s25237363
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