Chip-Based Optical Sensor Detects Cancer Biomarker

Pump light coupled to the device produced lasing in a microring resonator. The surface of the resonator holds probes that capture the analytes of interest. The laser light in the ring extends into the fluid. (Source: R. Seubers, Univ. Twente)

For the first time, researchers have used a chip-based sensor with an integrated laser to detect very low levels of a cancer protein biomarker in a urine sample. The new technology is more sensitive than other designs and could lead to non-invasive and inex­pensive ways to detect molecules that indicate the presence or progres­sion of a disease.

“Current methods to measure biomarker levels are expensive and sophis­ticated, requiring biopsies and analysis in specialized labora­tories,” said team leader Sonia M. Garcia-Blanco from the University of Twente in the Nether­lands. “The new tech­nology we developed paves the way to faster and ultra-sensitive detection of panels of biomarkers that will permit doctors to make timely decisions that improve perso­nalized diagnosis and treatment of medical conditions including cancer.”

The multi-insti­tutional group of researchers funded by the H2020 European project GLAM (Glass multiplexed biosensor), shows that the new sensor can perform label-free detection of S100A4, a protein associated with human tumor develop­ment, at levels that are clini­cally relevant. “The biosensor could enable point-of-care devices that simultaneously screen for various diseases,” said Garcia-Blanco. “Its operation is simple and does not require complicated sample treatments or sensor operation, making it an excellent candidate for clinical appli­cations.” The researchers say that the sensor holds potential for non-biomedical appli­cations, as well. For example, it can also be used to detect different types of gases or liquid mixtures.

The new chip-based sensor detects the presence of specific molecules by illu­minating the sample with light from an on-chip micro­disk laser. When the light interacts with the biomarker of interest the color, or frequency, of this laser light shifts in a detectable way. To perform detection in urine samples, the researchers had to figure out how to integrate a laser that could operate in a liquid environ­ment. They turned to the photonic material aluminum oxide, because when doped with ytterbium ions it can be used to fabricate a laser that emits in a wave­length range outside the light absorption band of water while still enabling the precise detection of the biomarkers.

“Although sensors based on moni­toring frequency shifts of lasers already exist, they often come in geometries that are not easily integrated on small, disposable photonic chips,” said Garcia-Blanco. “Aluminum oxide can easily be fabricated mono­lithically on-chip and is compatible with standard electronic fabri­cation procedures. This means that the sensors can be produced on a large, industrial scale.” Using a microdisk laser rather than the non-lasing ring resonators used in other similar sensors opens the door to unpre­cedented sensi­tivity. The sensi­tivity comes from the fact that the lasing linewidth is much narrower than the resonances of passive ring resonators. Once other noise sources, such as thermal noise, are eliminated, this method will allow the detection of very small frequency shifts from biomarkers at very low concen­trations.

After developing and applying a surface treatment that captures the biomarkers of interest in complex liquids such as urine, the researchers tested the new sensor with synthetic urine containing known biomarker levels. They were able to detect S100A4 at concentrations as low as 300 picomolar. “Detection in this concen­tration range shows the potential of the platform for label-free biosensing,” said Garcia-Blanco. “Furthermore, the detection module can be poten­tially made very simple using the developed tech­nology, bringing it a step closer to the final application outside of the labora­tory.”

The researchers are working to incor­porate all the relevant optical sources and signal generation components onto the chip to make the device even simpler to operate. They also want to develop various coatings that could allow parallel detection of a large variety of biomarkers. (Source: OSA)

Reference: M. de Goede et al.: Al2O3:Yb3+ integrated microdisk laser label-free biosensor, Opt. Lett. 44, 5937 (2019); DOI: 10.1364/OL.44.005937

Link: Optical Sciences Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands

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