Biosensing (lab on chip)
Early detection of cancer is crucial for improving treatment effectiveness, as it allows for intervention before metastasis, when therapies are generally more successful and less invasive. However, conventional methods like biopsies and imaging have significant drawbacks in terms of invasiveness, cost, and sensitivity to early-stage changes. In this context, Lab-On-Chip (LoC) devices represent a promising alternative. These miniaturized platforms enable fast, precise, and minimally invasive analyses by integrating multiple laboratory functions onto a single chip. Their compact, automated nature makes them ideal for point-of-care applications and broad access to timely, cost-effective diagnostics.
The sensor represents the key functional element in LoC system, as it enables the detection of tumor biomarkers, specific molecules released by tumors into bodily fluids. One of the main challenges is detecting these biomarkers at extremely low concentrations, especially during the early stages of cancer development. This requires sensors with ultra-high sensitivity. Advanced photonic technologies, such as evanescent-field optical sensors, are particularly well suited for this purpose. They offer excellent sensitivity, resolution, and reliability, allowing the identification of small changes in biological samples. Furthermore, their compatibility with CMOS electronics and microfluidic platforms supports seamless integration into LOC systems, enabling the development of portable, low-cost diagnostic devices that are robust against external interferences.
Among the most explored photonic solutions for biosensing applications are photonic crystals, ring resonators and plasmonic structures, which exploit light-matter interactions to achieve high sensitivity and specificity. In recent years, several photonic biosensing platforms have been developed within our laboratory, with a focus on early diagnosis and monitoring of diseases through the detection of protein biomarkers, extracellular vesicles, gases, and metabolites in biological fluids. These devices are designed for integration into LoC systems, offering high sensitivity, compactness, and label-free operation. A Bragg grating sensor integrated into a PMMA waveguide was proposed for the detection of extracellular vesicles. This configuration achieved sensitivities ranging from 230.7 to 860.6 nm/RIU over a refractive index range of 1.32 to 1.44, depending on the cladding setup [1]. Another configuration based on ring resonator technology was developed for glucose sensing, employing a hybrid microring implemented in SOI (Silicon-On-Insulator) technology. This device demonstrated a Q-factor of 10⁵, a sensitivity of 120 nm/RIU, and a limit of detection of 10⁻⁶ RIU, corresponding to a glucose concentration of 46 g/L [2]. A one-dimensional photonic crystal with engineered defects was developed for IgG detection, offering a box-like spectral response. The sensor demonstrated a sensitivity of 490.49 nm/RIU and an exceptionally high figure of merit (FOM) of 3892.78 RIU⁻¹ [3]. Another photonic crystal configuration, based on a high-Q 1D structure in AMTIR-1 chalcogenide glass, was optimized for nitric oxide (NO) sensing in exhaled breath. It achieved a Q-factor of 1.1 × 10⁴ and a Q/V ratio of 1.4 × 10⁴(λ/n) ⁻³ [4].
For the detection of IgG, metasurface-based solutions have also been explored. One device, using hydrogenated amorphous silicon nanocuboids, exploits high-Q anapole states and achieves a surface sensitivity of 35.13 nm/RIU [5]. Another configuration reaches a Q-factor of 3.19 × 10³, a resonance amplitude above 0.7 a.u., and a surface sensitivity of 25 nm/RIU, enabling compact and non-invasive detection in biological fluids [6].
Ongoing research is also exploring advanced concepts to further enhance biosensing capabilities. One line of investigation focuses on optical sensors based on topological edge states, which combine high sensitivity with intrinsic robustness to environmental and fabrication-related perturbations. In parallel, a hybrid plasmonic–dielectric configuration is being developed, integrating a gold metasurface within a silicon waveguide to achieve strong field confinement and efficient label-free detection of biomolecules in solution. Complementing these efforts, an optofluidic platform is under design for early cancer diagnosis, aimed at separating exosome-sized nanoparticles based on their size and subsequently quantifying them through an integrated electrowetting-based counting system.
References:
[1] N. Saha, G. Brunetti, A. Kumar, M. N. Armenise and C. Ciminelli, “Highly Sensitive Refractive Index Sensor Based on Polymer Bragg Grating: A Case Study on Extracellular Vesicles Detection,” Biosensors, vol.12, no. 6, p. 415, 2022, doi: https://doi.org/10.3390/bios12060415
[2] C. Ciminelli, F. Dell’Olio, D. Conteduca, C. M. Campanella and M. N. Armenise, “High performance SOI microring resonator for biochemical sensing,” Optics & Laser Technology, vol. 59, pp. 60-67, 2014, doi: https://doi.org/10.1016/j.optlastec.2013.12.011
[3] A. di Toma, G. Brunetti, P. Colapietro, and C. Ciminelli, “High-Resolved Near-Field Sensing by Means of Dielectric Grating with a Box-Like Resonance Shape,” IEEE Sensors Journal, vol. 24, no. 5, pp. 6045–6053, 2024, doi: 10.1109/JSEN.2024.3349948 High-Resolved Near-Field Sensing by Means of Dielectric Grating With a Box-Like Resonance Shape | IEEE Journals & Magazine | IEEE Xplore
[4] D. Conteduca, F. Dell’Olio, C. Ciminelli and M. N. Armenise, “A new miniaturized exhaled nitric oxide sensor based on a high Q/V mid-infrared 1D PhC cavity,” Applied Optics, vol. 54, no. 9, pp. 2208-2217, 2015, doi: https://doi.org/10.1364/AO.54.002208
[5] G. Brunetti, C. Panciera, C. Ciminelli, “Versatile Metasurfaces for Liquid Biopsy Applications,” 24th International Conference on Transparent Optical Networks (ICTON 2024), IEEE, pp. 1-4, 2024, doi: 10.1109/ICTON62926.2024.10647788 Versatile Metasurfaces for Liquid Biopsy Applications | IEEE Conference Publication | IEEE Xplore
[6] G. Brunetti, N. Saha, P. Colapietro, and C. Ciminelli, “Optical Slot-Assisted Metasurface for IgG Protein Detection,” Journal of Physics: Conference Series, vol. 2725, no. 1, pp. 012001, 2024, doi: 10.1088/1742-6596/2725/1/012001 Optical Slot-Assisted Metasurface for IgG Protein Detection – IOPscience