Shining the Path of Precision Diagnostic: Advancements in Photonic Sensors for Liquid Biopsy

Abstract

Liquid biopsy (LB) has gained attention as a valuable approach for cancer diagnostics, providing a minimally invasive option compared to conventional tissue biopsies and helping to overcome issues related to patient discomfort and procedural invasiveness. Recent advances in biosensor technologies, particularly photonic sensors, have improved the accuracy, speed, and real-time capabilities for detecting circulating biomarkers in biological fluids. Incorporating these tools into clinical practice facilitates more informed therapeutic choices and contributes to tailoring treatments to individual patient profiles. This review highlights the clinical potential of LB, examines technological limitations, and outlines future research directions. Departing from traditional biosensor focused reviews, it adopts a reverse-mapping approach grounded in clinically relevant tumor biomarkers. Specifically, biomarkers associated with prevalent cancers, such as breast, prostate, and lung cancers, serve as the starting point for identifying the most suitable photonic sensing platforms. The analysis underscores the need to align sensor design with the physicochemical properties of each biomarker and the operational requirements of the application. No photonic platform is universally optimal; rather, each exhibits specific strengths depending on performance metrics such as sensitivity, limit of detection, and easy system integration. Within this framework, the review provides a comprehensive assessment of emerging photonic biosensors and outlines key priorities to support their effective clinical translation in cancer diagnostics.

Keywords: cancer detection; circulating tumor biomarkers; label-free photonic biosensors; liquid biopsy.

Figure 3

(a) Schematic representation of SPR biosensor. Adapted from [102] Licensed under CC BY 4.0; (b) experimental setup for optical fiber immunosensor-based system and a sequence of SEM images of the fabricated optical fiber. Adapted from [105] Licensed under CC BY-NC-ND 4.0; (c,d) SEM views of the nanocuboid array. Adapted from [110] Licensed under CC BY-NC-ND 4.0, [111].

Figure 4

(a) Schematic representation and cross-section view of the sub-wavelength grating. Adapted from [115] Licensed under CC BY 4.0; (b) scheme and optical microscope images of MRR. Adapted from [118] Licensed under CC BY 4.0; (c) fabricated fiber-optic LSPR sensor with integrated view of the sensor chip, optical setup, and FEM images of the gold nanoparticle functionalize fiber tip. Adapted from [119] Licensed under CC BY 4.0; (d) dark-field optical microscopy image of MRR array. Adapted from [120] Copyright 2021 Elsevier.

Figure 5

(a) Schematic diagram of the EVA 2.0 sensor system. Adapted from [131] Licensed under CC BY 4.0; (b) SEM image sequence illustrating the evolution of the surface thin film (STF) morphology in mAb- and Nb-based immunosensors. Shown are the STF structures before and after antibody or nanobody functionalization in both sensor types. Adapted from [133] Copyright 2024 Elsevier; (c) local and top views of THz metasurface biosensor. Adapted from [135] Copyright 2022 Elsevier.

Figure 1

Illustration of a biosensor structure, with its three key components: a biorecognition element; a transducer to convert the biorecognition interaction into a detectable signal; and a processor responsible for amplifying, processing, and presenting the signal.

Figure 2

(a) Representation of a label-free biosensor and (b) a label-based biosensor.

Figure 6

(a) Optical microscope image of fiber immunosensor. Adapted from [143] Copyright 2023 IEEE; (b) schematic representation of the open-cavity FPI. Adapted from [144] Copyright 2024 Elsevier; (c) SEM images illustrating the structural features of the fabricated senso.Adapted from [144] Copyright 2023 IEEE; (d) schematic representation of the toroidal metasurface and a microscope image of the fabricated toroidal unit cells. Adapted with permission from [145]. Copyright 2022 American Chemical Society; (e) SEM images of microneedle array. Adapted from [146] Licensed under CC BY 4.0.

Figure 7

(a) Schematic diagram of fiber laser-based biosensor system. Adapted from [105] Licensed under CC BY-NC-ND 4.0; (b) biosensing system based on refractometric method that presents eight flow channels integrated with silicon nanodisk array. Adapted with permission from [153]. Copyright 2017 American Chemical Society; (c) SEM microscope image of nanocylinders before and after substrate cleaning with piranha solution. Adapted with permission from [153]. Copyright 2017 American Chemical Society; (d) SEM images of the silicon nanodisk. Copyright 2017 American Chemical Society; (e) SEM images of the arrays of silicon nanocylinders. Adapted with permission from [154]. Copyright 2019 American Chemical Society.