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Ultrasensitive, Real-Time Molecular Sensing in Unprocessed Whole Blood Using Surface-Enhanced Raman Scattering

Mingyu Han^1,2, Eugeniu Balaur³, Connie Darmanin³

¹Commonwealth Scientific and Industrial Research Organization (CSIRO), Agriculture and Food, 671 Sneydes Road, Werribee, Victoria 3030, Australia.

|March 9, 2026

Summary

This study introduces a novel biomimetic sensor platform for ultrasensitive, real-time molecular detection in whole blood. The innovative design overcomes biofouling and expands dynamic range for improved diagnostics.

Keywords:

SERS anti-fouling aptamer lubricin real-time monitoring

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Area of Science:

Biomaterials Science
Analytical Chemistry
Biosensing

Background:

Real-time molecular sensing in unprocessed whole blood faces challenges like biofouling and limited dynamic range.
Existing methods struggle with sensitivity, stability, and rapid equilibration in complex biological matrices.

Purpose of the Study:

To develop a biomimetic surface-enhanced Raman scattering (SERS) platform for ultrasensitive, real-time detection in whole blood.
To address limitations of current biosensing technologies in complex biofluid analysis.

Main Methods:

Integration of structure-switching aptamers with a lubricin-derived glycocalyx-mimicking structure.
Utilizing surface-enhanced Raman scattering (SERS) for molecular detection.
Employing a biomimetic approach to prevent biofouling and enhance signal.

Main Results:

Achieved femtomolar detection in buffer and sub-nanomolar quantification in whole blood.
Expanded dynamic range by six orders of magnitude compared to electrochemical aptamer sensors.
Demonstrated prevention of biofouling, enhanced selectivity, and signal amplification through molecular crowding.

Conclusions:

The biomimetic-SERS platform enables amplification-free, real-time molecular sensing in complex biofluids.
This strategy holds significant potential for therapeutic drug monitoring and point-of-care diagnostics.
Lubricin's multifaceted role is key to the sensor's performance in unprocessed whole blood.