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arXiv:2107.06737 · Journal of Applied Physics

Experimental measurement of kinetic parameters using quantum plasmonic sensing

Kelvin Tafadzwa Mpofu, Changhyoup Lee, Glenn E. M. Maguire, Hendrik Gerhardus Kruger, Mark Tame

Published Feb 28, 2022• 22 citations
arXivHTMLPDF

Abstract

Kinetic models are essential for describing how molecules interact in a variety of biochemical processes. The estimation of a model’s kinetic parameters by experiment enables researchers to understand how pathogens, such as viruses, interact with other entities like antibodies and trial drugs. In this work, we report a simple proof-of-principle experiment that uses quantum sensing techniques to give a more precise estimation of kinetic parameters than is possible with a classical approach. The interaction we study is that of bovine serum albumin (BSA) binding to gold via an electrostatic mechanism. BSA is an important protein in biochemical research as it can be conjugated with other proteins and peptides to create sensors with a wide range of specificity. We use single photons generated via parametric down-conversion to probe the BSA–gold interaction in a plasmonic resonance sensor. We find that sub-shot-noise-level fluctuations in the sensor signal allow us to achieve an improvement in the precision of up to 31.8% for the values of the kinetic parameters. This enhancement can, in principle, be further increased in the setup. Our work highlights the potential use of quantum states of light for sensing in biochemical research.

DOI
10.1063/5.0079896

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Kinetic models are essential for describing how molecules interact in a variety of biochemical processes. The estimation of a model’s kinetic parameters by experiment enables researchers to understand how pathogens, such as viruses, interact with other entities like antibodies and trial drugs. In this work, we report a simple proof-of-principle experiment that uses quantum sensing techniques to give a more precise estimation of kinetic parameters than is possible with a classical approach. The interaction we study is that of bovine serum albumin (BSA) binding to gold via an electrostatic mechanism. BSA is an important protein in biochemical research as it can be conjugated with other proteins and peptides to create sensors with a wide range of specificity. We use single photons generated via parametric down-conversion to probe the BSA–gold interaction in a plasmonic resonance sensor. We find that sub-shot-noise-level fluctuations in the sensor signal allow us to achieve an improvement in the precision of up to 31.8% for the values of the kinetic parameters. This enhancement can, in principle, be further increased in the setup. Our work highlights the potential use of quantum states of light for sensing in biochemical research.
The measurement of parameters that describe kinetic processes is important in the study of molecular interactions. It enables a deeper understanding of the physical mechanisms underlying how different biological entities interact with each other, such as viruses with cells, vaccines with antibodies, or new drugs with specific diseases. In this work, we study theoretically the use of quantum sensing techniques for measuring the kinetic parameters of molecular interactions. The sensor we consider is a plasmonic resonance sensor---a label-free photonic sensor that is one of the most widely used in research and industry. The first type of interaction we study is the antigen BSA interacting with antibody IgG1, which provides a large sensor response. The second type is the enzyme carbonic anhydrase interacting with the tumor growth inhibitor benzenesulfonamide, which produces a small sensor response. For both types of interaction we consider the use of two-mode Fock states, squeezed vacuum states, and squeezed displaced states. We find that these quantum states offer an enhancement in the measurement precision of kinetic parameters when compared to that obtained with classical light. The results may help in the design of more precise quantum-based sensors for studying kinetics in the life sciences.
The work done in this paper is an extension of the work done by Mpofu et al in [1]. The motivation for this paper is to show the potential of quantum bio-sensing techniques in applications to complex viruses like the human immunodeficiency virus (HIV) and to show it's potential in binding reactions where the signal is small and can potentially be buried in noise. In this paper we show theoretically that using quantum states of light such as the Fock state improves the precision in the estimation of kinetic parameters measured from the sensorgrams produced by the Kretschmann conguration. Though the Fock state is not the only quantum state in this study we look only at the Fock state because it has been shown to be the state which offers the best enhancement [1]. We show here that the Fock state allows us to measure the parameters more accurately in comparison to the classical (Coherent) state of light. We consider in this paper a binding reaction involving HIV type 1 (HIV-1). Specifically we look at the binding reaction between a variant of HIV-1 protease and nelnavir which is an inhibitor. Such a study is also offers value for drug discovery research as it points to the development of new technologies which can be applied to testing the efficacy of new drugs. Quantum technologies can prove to be useful in the fight against the HIV pandemic and assist in the continual research towards the development of treatments and a cure.
Analyzing the kinetics of biological processes plays a significant role in understanding fundamental cellular functions. Many physics-based technologies used to study such processes are limited by the shot noise inherent to the coherent states of light. These technologies can greatly benefit from leveraging quantum probes to improve the sensitivity of measurements in cellular biology. The surface plasmon resonance technique has been used effectively to achieve label-free, real-time measurements of protein binding kinetics, which constitutes an important biological phenomenon occurring near the cell membrane. Here, we demonstrate the integration of this technique with the two-mode bright squeezed state having fewer fluctuations as compared to the coherent state to improve the sensitivity of measurement in studying a protein-gold adsorption process. We show 4 dB of squeezing as we record the signal-to-noise ratio as the function of time, and it is maintained throughout the kinetic process. The improved signal-to-noise ratio leads to a 60 % improvement in the sensitivity of measuring the observable rate constant k s . The quantum advantage as shown in terms of squeezing is achieved despite the total absorption of 74 % from the source until the final detection after the sensor. Overall, we provide the most practical setup for improving the sensitivity of the time-dependent measurements involved in various biological processes at the molecular level.
Abstract The signal-to-noise ratio is an important quantity in signal and image analysis that gives information about the quality of the signal and/or image of interest. When plasmonic biosensors are used to study how molecules interact in intermolecular binding reactions, the output signal and/or image must be of the highest quality to get the best value from our biosensors. Images of interest in this work are images of the binding region at the metal surface of the plasmonic biosensor. Improving the signal-to-noise ratio of these signals and/or images is a key area of research that can help scientists learn more about how different molecules interact with each other. Because these molecular entities can include a wide range of biomolecules, we can investigate different types of binding interactions. In this paper, we look at a theoretical two-mode image sensing framework that we use to model the signal-to-noise ratio in images generated by a plasmonic image-based biosensor. A Krestchmann configuration-based surface resonance sensor is used as a plasmonic biosensor. In the model, an example of how BSA and an antibody called IgG1 bind to the surface of a plasmonic biosensor are examined. Traditionally, classical states of light are used as probe states in the Krestchman configuration; in this paper, quantum states of light are considered alternative probe states. The effect of using quantum states of light, such as the Fock state, squeezed displaced states, and squeezed vacuum states, on the signal-to-noise ratio of images is investigated. This work also looks at the effect of losses in the sensing environment and changes in photon numbers in the input signal on the average signal-to-noise ratio of the output of the plasmonic biosensor. The novelty in the described work lies in the exploration of using a variety quantum states of light as probe states in a plasmonic image-based biosensor, specifically in the context of improving the signal-to-noise ratio of images captured from the binding region at the metal surface accounting for the impact of losses. It was found that some quantum states improve the signal-to-noise ratio of the plasmonic biosensor output image.
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.
Optical sensors have applications in a range of settings, from measuring mechanical vibrations in manufacturing processes to biometrics in security devices and the detection of proteins and viruses in biomedical research. Many sensing approaches exist and plasmonic systems in particular have been studied extensively due to their ability to confine light below the diffraction limit, which greatly enhances their sensitivity compared to conventional approaches. Recently, various quantum techniques have been discovered that can outperform classical sensing ones and provide sensitivity beyond the shot-noise limit. The use of these quantum techniques in plasmonics for improving sensing performance is currently being explored. We study the performance of a plasmonic sensor that exploits the quantum nature of light and its highly confined field. We consider specialized quantum states and by comparison we show how each can provide improved sensitivity beyond the shot-noise limit.