Label-free optical sensor systems have emerged that exhibit extraordinary sensitivity for detecting physical, chemical, and biological entities at the micro/nanoscale. Particularly exciting is the detection and analysis of molecules, on miniature optical devices that have many possible applications in health, environment, and security. These micro- and nanosensors have now reached a sensitivity level that allows for the detection and analysis of even single molecules. Their small size enables an exceedingly high sensitivity, and the application of quantum optical measurement techniques can allow the classical limits of detection to be approached or surpassed. The new class of label-free micro- and nanosensors allows dynamic processes at the single-molecule level to be observed directly with light. By virtue of their small interaction length, these micro- and nanosensors probe light-matter interactions over a dynamic range often inaccessible by other optical techniques. For researchers entering this rapidly advancing field of single-molecule micro- and nanosensors, there is an urgent need for a timely review that covers the most recent developments and that identifies the most exciting opportunities. The focus here is to provide a summary of the recent techniques that have either demonstrated label-free single-molecule detection or claim single-molecule sensitivity.
Label-free optical sensor systems have emerged that exhibit extraordinary sensitivity for detecting physical, chemical, and biological entities at the micro/nanoscale. Particularly exciting is the detection and analysis of molecules, on miniature optical devices that have many possible applications in health, environment, and security. These micro- and nanosensors have now reached a sensitivity level that allows for the detection and analysis of even single molecules. Their small size enables an exceedingly high sensitivity, and the application of quantum optical measurement techniques can allow the classical limits of detection to be approached or surpassed. The new class of label-free micro- and nanosensors allows dynamic processes at the single-molecule level to be observed directly with light. By virtue of their small interaction length, these micro- and nanosensors probe light-matter interactions over a dynamic range often inaccessible by other optical techniques. For researchers entering this rapidly advancing field of single-molecule micro- and nanosensors, there is an urgent need for a timely review that covers the most recent developments and that identifies the most exciting opportunities. The focus here is to provide a summary of the recent techniques that have either demonstrated label-free single-molecule detection or claim single-molecule sensitivity.
The ability to detect and characterize single molecules in their native environments is paramount for advancing fields ranging from fundamental biology to advanced materials science. Traditional single-molecule detection methods often face limitations in terms of sensitivity, spatial resolution, and the ability to perform measurements in situ, especially in complex biological matrices. This paper explores the transformative potential of quantum-enhanced nanosensors to overcome these limitations, enabling ultrasensitive single-molecule detection directly within living systems or operational devices. We review the fundamental principles of quantum phenomena, such as entanglement, squeezing, and quantum coherence, and discuss how they can be harnessed to push sensing capabilities beyond classical limits. Various architectures of quantum-enhanced nanosensors, including those based on nitrogen-vacancy (NV) centers in diamond, quantum dots, and optomechanical systems, are examined for their unique advantages in detecting minute perturbations caused by single molecules. The paper delves into methodologies for designing, fabricating, and functionalizing these nanosensors for specific targets, emphasizing strategies for achieving high spatial resolution and robust in situ operation. We present a theoretical framework for assessing the enhanced signal-to-noise ratio and reduced detection limits offered by quantum metrology. Potential applications span real-time monitoring of biochemical reactions, early disease diagnosis, and the development of next-generation analytical tools. Finally, the challenges and future directions for realizing widespread practical implementation of quantum-enhanced nanosensors for in situ single-molecule detection are critically discussed, highlighting the interdisciplinary efforts required at the intersection of quantum physics, nanotechnology, and life sciences.
Optical spectroscopy of single impurity molecules in low-temperature solids provides an exquisitely sensitive probe of the structure and dynamics of the specific local environment around the single molecule, unobscured by ensemble averaging. Effects such as spectral diffusion, perturbations by external fields, changes in molecular photophysics, optical switching, dynamics due to amorphous system physics, magnetic resonance of a single molecular spin, and perturbations due to nearby charge transport have all been observed. Because properly chosen single molecules act as two- and three-level quantum systems, a variety of quantum optical effects may be observed, such as photon antibunching, optical Stark effect, and single-photon emission on command. When they carry spin in their ground and excited states, single molecules and other nano-objects open many more experiments in quantum optics and nanophysics, because they are sensitive to magnetic interactions and can serve as readouts for spin systems with long coherence times. As a new class of nanoscale experiments, the ability to optically pump and probe single 2–3-nm-sized molecules in complex systems provides a new window into the local dynamics and heterogeneity of solids.
Abstract Quantum sensing (QS) is a rapidly developing field at the intersection of physics, biology, and nanotechnology. It holds great promise for improving how we detect biomolecules in health, diagnostics, and environmental monitoring, and this potential is reflected in the rapid development and growing interest in advanced biosensing technologies. Traditional sensing methods, while useful, often face limits in sensitivity, speed, and the ability to analyze tiny amounts or subtle changes in biomolecules. QS uses coherence, entanglement, and superposition to achieve much higher sensitivity and precision than classical techniques. These technologies rely on advanced platforms like nitrogen-vacancy centers in diamonds, quantum dots. They can measure tiny changes in magnetic fields, electric charges, or fluorescence signals caused by biomolecules like proteins, DNA, lipids, carbohydrates and metabolites. This review explains the fundamental principles behind QS and explores how various physical platforms are used to detect and study biomolecules. It highlights recent breakthroughs in detecting single molecules, monitoring enzymatic reactions in real time, and imaging biological structures with quantum-level detail. We also discuss how nanotechnology is powering the field, improving integration through nanoparticle coupling, microfluidics, and specialized bio interfaces to target and amplify signals in practical settings. This review discusses current efforts to overcome existing challenges and highlights future directions, including the development of quantum-enhanced clinical sensors, integration with artificial intelligence for data analysis, and hybrid quantum–classical sensing strategies. These advances are expected to accelerate the translation of quantum biosensing technologies from laboratory demonstrations to practical clinical and environmental applications in the coming decade.
In the field of optics and photonics, plasmonic sensors have garnered considerable interest due to their outstanding sensitivity and impressive capacity to control light at the nanoscale. These sensors enable the integration of biochemical sensing platforms by exploiting the combination of enhanced and localized electromagnetic fields at the metal–dielectric interface, and they operate effectively below the diffraction limit. The performance of conventional plasmonic sensors, despite their practical development and commercial success, remains inherently constrained by classical noise constraints, owing to the quantum fluctuations of light, known as the shot-noise limit. Recent advances have introduced quantum optical resources such as entangled and squeezed light states to overcome inherent classical restrictions, thus giving rise to the quantum plasmonic sensing field. This interdisciplinary field combines the ability to enhance electric field capabilities with the precision of quantum metrology, enabling ultrasensitive chemical and biological detection that surpasses classical precision thresholds. In the last decades, theoretical models and experimental demonstrations have greatly advanced the development of quantum plasmonic sensors, improving our comprehension of quantum light–matter interactions and facilitating novel nanoscale sensing designs. This chapter provides a comprehensive overview of the fundamental principles, latest developments, and major concepts that have driven progress in quantum plasmonic sensing and shows that quantum components are being integrated into plasmonic systems, thereby transforming optical sensing to the quantum level.
The extraordinary sensitivity of plasmonic sensors is well-known in the optics and photonics community. These sensors exploit simultaneously the enhancement and the localization of electromagnetic fields close to the interface between a metal and a dielectric. This enables, for example, the design of integrated biochemical sensors at scales far below the diffraction limit. Despite their practical realization and successful commercialization, the sensitivity and associated precision of plasmonic sensors are starting to reach their fundamental classical limit given by quantum fluctuations of light-known as the shot-noise limit. To improve the sensing performance of these sensors beyond the classical limit, quantum resources are increasingly being employed. This area of research has become known as "quantum plasmonic sensing", and it has experienced substantial activity in recent years for applications in chemical and biological sensing. This review aims to cover both plasmonic and quantum techniques for sensing, and it shows how they have been merged to enhance the performance of plasmonic sensors beyond traditional methods. We discuss the general framework developed for quantum plasmonic sensing in recent years, covering the basic theory behind the advancements made, and describe the important works that made these advancements. We also describe several key works in detail, highlighting their motivation, the working principles behind them, and their future impact. The intention of the review is to set a foundation for a burgeoning field of research that is currently being explored out of intellectual curiosity and for a wide range of practical applications in biochemistry, medicine, and pharmaceutical research.
While the fundamental principles of light-matter interaction are well-understood and drive countless technologies, the world of multiphoton processes remains a fascinating puzzle, holding the potential to drastically alter our understanding of how light interacts with matter at its most basic level [1–4]. This rich interplay of light and matter unveils novel phenomena that can be harnessed for sensing with exceptional precision, as exemplified by multiphoton quantum sensing. This thesis delves into the applications of multiphoton quantum protocols, particularly in imaging, communication, and plasmonic sensing, to surpass classical limitations and achieve enhanced sensitivity. We explore the potential of multiphoton quantum processes, particularly in the nanoscale regime and within subsystems of macroscopic systems, where novel and ultra-sensitive sensing methodologies emerge. Subsequent chapters of this thesis demonstrate the transformative potential of multiphoton quantum sensing, elucidating the design, implementation, and experimental results of specific sensing protocols tailored to diverse applications. Our analysis combines experimental observations and theoretical predictions to assess the sensitivity and performance of these protocols. Additionally, the thesis discusses potential future directions and advancements in the field, envisioning applications in biomolecule detection, environmental monitoring, and fundamental studies of light-matter interactions at the nanoscale. Concluding reflections highlight the implications of multiphoton quantum sensing across scientific disciplines and lay the groundwork for future research endeavors.