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Frontiers in Optics

Towards Quantum Enhanced Real-Time Sensing of Protein Binding Kinetics

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

Published Jan 1, 2025• 0 citations
Publisher

Abstract

We demonstrate that the two-mode bright squeezed light in combination with surface plasmon resonance technique leads to a 60% improvement in the sensitivity of measuring kinetic parameters of the time-dependent protein-binding process.
DOI
10.1364/fio.2025.jw5a.20

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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.
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.
Surface plasmon resonance (SPR) sensors can reach the quantum noise limit of the optical readout field in various configurations. We demonstrate that two-mode intensity squeezed states produce a further enhancement in sensitivity compared with a classical optical readout when the quantum noise is used to transduce an SPR sensor signal in the Kretschmann configuration. The quantum noise reduction between the twin beams when incident at an angle away from the plasmonic resonance, combined with quantum noise resulting from quantum anticorrelations when on resonance, results in an effective SPR-mediated modulation that yields a measured sensitivity 5 dB better than that with a classical optical readout in this configuration. The theoretical potential of this technique points to resolving particle concentrations with more accuracy than is possible via classical approaches to optical transduction.