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arXiv:2410.22694 · PRX Life

Quantum Enhanced Real-Time Sensing of Protein-Gold Adsorption Kinetics

Mrunal Kamble, Evan Humberd, Tian Li, G. S. Agarwal

Published May 29, 2025• 3 citations
arXivHTMLPDF

Abstract

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.

DOI
10.1103/prxlife.3.023010

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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.
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 use of optical sensing for in vivo applications is compelling, since it offers the advantages of non-invasiveness, non-ionizing radiation, and real-time monitoring. However, the signal-to-noise ratio (SNR) of the optical signal deteriorates dramatically as the biological tissue increases. Although increasing laser power can improve the SNR, intense lasers can severely disturb biological processes and viability. Quantum sensing with bright squeezed light can make the measurement sensitivity break through the quantum noise limit under weak laser conditions. A bright squeezed light source is demonstrated to avoid the deterioration of SNR and biological damage, which integrates an external cavity frequency-doubled laser, a semi-monolithic standing cavity with periodically poled titanyl phosphate (PPKTP), and a balanced homodyne detector (BHD) assembled on a dedicated breadboard. With the rational design of the mechanical elements, the optical layout, and the feedback control equipment, a maximum non-classical noise reduction of −10.7 ± 0.2 dB is observed. The average squeeze of −10 ± 0.2 dB in continuous operation for 60 min is demonstrated. Finally, the intracavity loss of degenerate optical parametric amplifier (DOPA) and the initial bright squeezed light can be calculated to be 0.0021 and −15.5 ± 0.2 dB, respectively. Through the above experimental and theoretical analysis, the direction of improving bright squeeze level is pointed out.
Quantum states of light allow for highly sensitive biosensing configurations, surpassing the limitations imposed by shot-noise. In this theoretical study, we focus on optical plasmonic sensors, which have extensive applications in disease diagnostics, including detection of diseases like HIV. Our investigation involves simulating the impact of quantum states of light, such as the NOON state and squeezed states, on enhancing the limit of detection in a plasmonic phase-sensing biosensor, surpassing coherent light states’ shot-noise limit. Specifically, we explore the use of quantum states to improve the limit of detection in phase-based biosensors for HIV detection, operating below the shot-noise limit. Through our analysis, we demonstrate that incorporating quantum states of light in surface plasmon resonance (SPR) biosensing leads to enhanced performance compared to classical states. Moreover, we take into account the impact of environmental losses in the biosensing setup, considering the real-world challenges in practical implementation. Our findings emphasize the potential of quantum SPR biosensors in the development of novel disease diagnostics devices.
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.