Light-based sensors detect extremely low levels of traumatic brain injury biomarkers

23 June 2026

Light-based sensors detect extremely low levels of traumatic brain injury biomarkers

Advance lays the groundwork for ultra-sensitive biosensors to guide treatment decisions after head injuries

WASHINGTON - Researchers have developed a chip-based metasurface biosensor that can detect traumatic brain injury (TBI) biomarkers at extremely low levels. With further development, the technology could one day help doctors make a faster diagnosis after a head injury, helping to guide treatment and provide early warning when complications occur.

Metasurfaces are ultra-thin materials patterned with tiny features that enable them to manipulate light in ways conventional lenses cannot. Coating a metasurface with antibodies that bind to specific target molecules allows it to detect those molecules using light.

"Although several biomarkers have been validated as indicators of TBI, current methods for measuring them are time-consuming and require multiple complex laboratory steps," said research team leader Guangyuan Li from the Beijing Institute of Technology, Zhuhai, in China. "To address this challenge, we developed metasurface biosensors that are exceptionally sensitive, allowing them to produce clear, reliable optical signals even when only tiny amounts of a biomarker are present."

In the journal Optical Materials Express, the team, jointly led by Li and Yunhui Liu from Shenzhen Institute of Technology, CAS, reports that their new sensor can detect the TBI biomarkers glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein β (S100β) at levels as low as femtograms per milliliter - roughly a quadrillionth of a gram in a milliliter of fluid. The platform could also be adapted to create metasurface-based sensors capable of detecting multiple biomarkers simultaneously.

"If developed into a point-of-care format, this technology could help provide faster and accurate answers after brain injury - perhaps using just a finger prick," said Liu. "This could potentially reduce unnecessary CT scans for low-risk cases while flagging higher-risk patients earlier. It could also enable more accessible biomarker detection in ambulances, rural clinics, sports settings or emergency departments where time matters."

Creating a chip-based biosensor

Detecting TBI biomarkers in a clinically useful manner requires a sensor that is extremely sensitive to low molecular concentrations. To accomplish this, the researchers developed a metasurface biosensing device based on a corrugated gold surface. Because of its high-quality (high-Q) factor, when light shines on the surface, the reflection spectrum exhibits an extremely narrow dip.

If target biomolecules bind to the functionalized surface, the local refractive index will change slightly, leading to a shift in the dip wavelength. Because the dip is very narrow, even a very small shift can be distinguished, enabling ultrasensitive detection.

To create the high-Q corrugated gold surface, the researchers developed a fabrication technique that reduced surface roughness and optical losses. They used a highly precise nanofabrication approach to create the periodic pattern.

"We also developed a stable surface chemistry approach that allowed specific capture of the target molecules with low nonspecific adsorption and an optical setup that collects spectra with high signal-to-noise," said Li. "Together, these innovations made it possible to create ultra-sensitive biosensors in a compact chip."

Sensitive TBI biomarker detection

To test their new platform, the researchers prepared two separate sensors functionalized with anti-S100β and anti-GFAP antibodies and measured each biomarker at concentrations ranging from 1 fg/mL to 100 ng/mL. They also used non-target TBI biomarkers H-FABP and UCH-L1 as controls.

The platform showed clear, concentration-dependent wavelength shifts and subfemtogram per milliliter detection limits for S100β and GFAP, with markedly larger responses to the targets than to the controls.

The researchers note that although the process of fabricating the gold metasurfaces is scalable, it is also expensive. However, they are working to reduce the costs. Improvements to packaging and fluid-handling systems will also need to be developed before clinical use, and the technology will need to be validated using more complex, clinically relevant samples. Additional studies involving patient cohorts will also be required to assess the system's repeatability, robustness, and real-world performance.

Paper: S. Lin, H. Yang, Q Huang, W. Wang, Y. Liu, G Li, "Ultrasensitive Detection of Traumatic Brain Injury Biomarkers Using a High-Q Optical Metasurface," Opt. Mater. Express 16, 2151 - 2163 (2026).

DOI: 10.1364/OME.601906.

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