Patricia Ramirez-Priego

Silicon photonic biosensors are emerging as transformative platforms for next-generation diagnostics, combining label-free, real-time detection with high sensitivity, mass scalability, and complementary metal-oxide-semiconductor compatibility. This review examines the multidisciplinary ecosystem driving their continuous advancement, from interferometric and resonant architectures achieving attomolar detection limits, to optimized device performance and multiplexing strategies that enable simultaneous multi-analyte detection on a single chip. We analyze critical enabling technologies, including surface biofunctionalization protocols, microfluidic integration, optoelectronic packaging, and system-level architectures ranging from fully integrated monolithic solutions to hybrid cartridge-based platforms. In this way, this work maps the trajectory toward miniaturized biosensor systems capable of addressing complex challenges in point-of-care diagnostics, personalized medicine, and global health equity.

Localized surface plasmon resonance (LSPR) biosensors enable label-free, real-time, highly sensitive, and specific detection of biomolecular interactions. Recent advances in nanofabrication, hybrid materials, and computational modeling have led to achievements like femtomolar detection limits and artificial intelligence (AI) optimization. Despite this, clinical translation remains limited. Fewer than 5% of reported LSPR biosensors have undergone multi-site validation, and none have regulatory approval for routine clinical use. This Perspective critically examines the current state and future directions of LSPR biosensors, with particular attention to whether novel strategies, including hybrid plasmonic architectures, plasmon–phonon and plasmon–exciton coupling, and AI integration, can bridge the translational gap. Quantitative performance data are consolidated, major knowledge gaps are identified, and the need to prioritize standardization, reproducibility, and clinical validation over minor sensitivity improvements is argued for achieving meaningful diagnostic impact.

Plasmonic biosensors have demonstrated versatility across diverse applications, including clinical diagnostics, environmental monitoring, and food analysis. Multiplexed plasmonic biosensors capable of detecting multiple analytes simultaneously have also been developed. However, existing designs face challenges for wide‐scale adoption due to bulky designs and expense. A compact multichannel plasmonic biosensor platform is presented for multiplexed detection of up to four biomarkers from one sample distributed via microfluidic channels. The device operates under the Kretschmann configuration for sequential quasi‐simultaneous multichannel sensing. Optical performance evaluation demonstrates high sensitivity and a limit of detection (LOD) of 10⁻⁶ RIU across four channels. The biosensing capabilities of the device have been assessed for detecting four inflammatory biomarkers. Customized biofunctionalization of sensor chips ensures inter‐channel reproducibility and direct binding detection assays for C‐reactive protein (CRP), interleukin‐6 (IL‐6), procalcitonin (PCT), and pancreatic stone protein (PSP), with sensitivities in the low ng/mL range and negligible cross‐reactivity. Recovery testing confirms its feasibility for detecting multiple biomarkers at low concentrations in human serum. The compact, user‐friendly design makes this biosensor an attractive tool for multiplexed detection, underscoring its applicability beyond inflammatory‐related processes, offering a versatile solution for biomarker analysis in human fluids, and contributing to the decentralization of diagnostics for complex diseases.

The coronavirus (CoV) disease 2019 (COVID-19) is expected to become endemic in the coming years, meaning that the worldwide society shall be prepared to routinely manage the highly contagious respiratory SARS-CoV-2. A rapid and early diagnosis of the SARS-CoV-2 infection is crucial for controlling the spread of the disease, interrupting the transmission chain, and providing timely medical attention to patients. We introduce an innovative nanophotonic biosensor for the quantitative detection of viral particles in less than 20 minutes total assay time. The nanosensor, based on the bimodal waveguide (BiMW) interferometric technology, has been functionalized with novel bioengineered nanobodies (Nb) targeting the SARS-CoV-2 receptor-binding domain (RBD). Our approach relies on the direct capture of the viral particles, and the optimized methodology allows the detection of the SARS-CoV-2 virus with outstanding sensitivity, below 200 TCID50 per mL, being able to provide accurate viral load determination within a broad dynamic range (10²–10⁶ TCID50 per mL). Both the nanobodies and the sensor nanotechnology can be produced at a large scale with highly-efficient cost-effective procedures, and they are being integrated into a user-friendly point-of-care device for multiplexed and decentralized operation. The implementation of this unique biosensor in primary care assistance, hospitals, pharmacies, or private laboratories could greatly aid in the relief and descongestion of the sanitary systems and the clinical and social management of COVID-19.

Biosensors employing photonics integrated circuits, and specifically those that rely on interferometric evanescent wave working principles, have outstanding performances due to the extreme sensitivity exhibited in one-step and direct assay, without the need of amplification. Within the interferometric configurations, the Bimodal Waveguide (BiMW) interferometric sensor stands out due to its demonstrated sensitivity for real-life applications and the simplicity of its design. To overcome the ambiguities that arise from the periodic nature of interferometric read-outs, a new all-optical modulation and the subsequent trigonometry-based algorithm have been proposed and applied to the BiMW biosensor. This new algorithm has been successfully employed for the selective identification and quantification of the external Spike (S) protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our biosensing results from this simple, quick, and user-friendly method demonstrate high sensitivity and specificity and pave the way towards a point-of-care device for general use.