Techniques to observe and track single unlabelled biomolecules are crucial for many areas of nanobiotechnology; offering the possibility for lab-on-a-chip medical diagnostics operating at their ultimate detection limits, and to shed light on important nanoscale biological processes such as binding reactions, conformational changes, and motor molecule dynamics. Impressive progress has been made over the past few years to extend the sensitivity of such techniques, primarily via the evanescent field enhancement provided by optical microcavities [1, 2] or plasmonic resonators [3]. However, such approaches expose the biological system to greatly increased optical intensity levels, which can severely impact biological function, growth, structure and viability [4]. Here, we introduce an evanescent biosensing platform that operates at the fundamental precision limit introduced by quantisation of light. This allows a five order-of magnitude reduction in optical intensity whilst maintaining state-of-the-art sensitivity and enabling quantum noise limited tracking of single biomolecules as small as 3.5 nm.
Techniques to observe and track single unlabelled biomolecules are crucial for many areas of nanobiotechnology; offering the possibility for lab-on-a-chip medical diagnostics operating at their ultimate detection limits, and to shed light on important nanoscale biological processes such as binding reactions, conformational changes, and motor molecule dynamics. Impressive progress has been made over the past few years to extend the sensitivity of such techniques, primarily via the evanescent field enhancement provided by optical microcavities [1, 2] or plasmonic resonators [3]. However, such approaches expose the biological system to greatly increased optical intensity levels, which can severely impact biological function, growth, structure and viability [4]. Here, we introduce an evanescent biosensing platform that operates at the fundamental precision limit introduced by quantisation of light. This allows a five order-of magnitude reduction in optical intensity whilst maintaining state-of-the-art sensitivity and enabling quantum noise limited tracking of single biomolecules as small as 3.5 nm.
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.
Quantum metrology allows high sensitivity measurements to proceed with a lower light intensity than classically possible [1]. An important frontier for this technology is in biological measurements, where photochemical interactions often disturb biological processes and can damage the specimen [2]. Here we report the first demonstration of biological measurement with precision surpassing the quantum noise limit [3]. This was enabled through the development of a new microscopy system which extended previous methods used to track the motion of highly reflective mirrors with non-classical light to measurements of microscopic particles with non-paraxial fields (see Fig. 1). Biological dynamics in the critical Hz-kHz frequency range were made accessible by applying a quantum optical lock-in technique for the first time. This straightforward technique allowed quantum enhancement over a frequency range which reached as low as the range reported for squeezed light sources developed for gravity wave interferometers [4].
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.
Abstract Quantum‐enhanced sensing and metrology pave the way for promising routes to fulfil the present day fundamental and technological demands for integrated chips which surpass the classical functional and measurement limits. The most precise measurements of optical properties such as phase or intensity require quantum optical measurement schemes. These non‐classical measurements exploit phenomena such as entanglement and squeezing of optical probe states. They are also subject to lower detection limits as compared to classical photodetection schemes. Biosensing with non‐classical light sources of entangled photons or squeezed light holds the key for realizing quantum optical bioscience laboratories which could be integrated on chip. Single‐molecule sensing with such non‐classical sources of light would be a forerunner to attaining the smallest uncertainty and the highest information per photon number. This demands an integrated non‐classical sensing approach which would combine the subtle non‐deterministic measurement techniques of quantum optics with the device‐level integration capabilities attained through nanophotonics as well as nanoplasmonics. In this back drop, we review the underlining principles in quantum sensing, the quantum optical probes and protocols as well as state‐of‐the‐art building blocks in quantum optical sensing. We further explore the recent developments in quantum photonic/plasmonic sensing and imaging together with the potential of combining them with burgeoning field of coupled cavity integrated optoplasmonic biosensing platforms.
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.