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Abstract The COVID-19 pandemic has profoundly impacted global economies and healthcare systems, revealing critical vulnerabilities in both. In response, our study introduces a sensitive and highly specific detection method for cDNA, leveraging Luminescence Resonance Energy Transfer (LRET) between upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs), and achieves a detection limit of 242 fM for SARS-CoV-2 cDNA. This innovative sensing platform utilizes UCNPs conjugated with one primer and AuNPs with another, targeting the 5′ and 3′ ends of the SARS-CoV-2 cDNA, respectively, enabling precise differentiation of mismatched cDNA sequences and significantly improving detection specificity. Through rigorous experimental analysis, we established a quenching efficiency range from 10.4 % to 73.6 %, with an optimal midpoint of 42 %, thereby demonstrating the superior sensitivity of our method. Our work uses SARS-CoV-2 cDNA as a model system to demonstrate the potential of our LRET-based detection method. This proof-of-concept study highlights the adaptability of our platform for future diagnostic applications. Instrumental validation confirms the synthesis and formation of AuNPs, addressing the need for experimental verification of the preparation of nanomaterial. Our comparative analysis with existing SARS-CoV-2 detection methods revealed that our approach provides a low detection limit and high specificity for target cDNA sequences, underscoring its potential for targeted COVID-19 diagnostics. This study demonstrates the superior sensitivity and adaptability of using UCNPs and AuNPs for cDNA detection, offering significant advances in rapid, accessible diagnostic technologies. Our method, characterized by its low detection limit and high precision, represents a critical step forward in developing next-generation biosensors for managing current and future viral outbreaks. By adjusting primer sequences, this platform can be tailored to detect other pathogens, contributing to the enhancement of global healthcare responsiveness and infectious disease control. 

There is an increasing interest in the sensing of magnetic, electric, and temperature effects in biological systems on the nanoscale. While there are existing classical sensors, the possibility of using quantum systems promises improved sensitivity and faster acquisition time. So far, much progress has been made in diamond color centers like the nitrogen-vacancy (NV) which not only satisfy key requirements for biosensing, like extraordinary photostability and non-toxicity, but they also show promise as room-temperature quantum computers/sensors. Unfortunately, the most-impressive demonstrations have been done in bulk diamond, since NVs in fluorescent nanodiamonds (FNDs) tend to have inferior properties. Yet FNDs are required for widespread nanoscale biosensing. In order for FND-based quantum sensors to approach the performance of bulk diamond, novel approaches are needed for their fabrication. To address this need we discuss opportunities for engineering the growth of FNDs.