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].
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].
This thesis reports the development of a quantum enhanced microparticle tracking technique, which applied to measurements within living cells, allowed the first demonstrations of both biological measurements beyond the quantum noise limit and quantum enhanced spatial resolution within biology. The sensitivity of any optical measurement is limited by noise which follows from quantization of the electromagnetic field. This thesis theoretically characterizes the resulting quantum limit on particle tracking precision; both in the limit of perfect measurements and for the measurements used in real experiments, and theoretically establishes an experimental strategy which could allow the quantum limit to be surpassed via the application of non-classical light. Further, a computational tool is developed which allows rapid characterization of particle tracking experiments, thus providing researchers the benefit of rigorous theoretical predictions without requiring detailed calculations. Following this, classical technologies are developed which can improve microparticle tracking sensitivity and which are enabling steps toward integration of non-classical light. An interferometric strategy is described whereby signal-to-noise is improved by removing unwanted light from the detector. An optical lock-in technique is developed which eliminates low-frequency noise, thus allowing quantum noise limited performance at low frequencies. This is a crucial requirement for quantum enhanced measurements, and can also improve precision in classical experiments. Dark-field illumination is also explored as a method to remove unwanted background light, and the optimal illumination angle is calculated for our intended experiments. These advances are then applied in the development of the first quantum enhanced particle tracking apparatus. Squeezed states of light are used to improve particle tracking precision by 2.7 dB, demonstrating quantum enhanced microscopy for the first time. This was applied to perform the first measurements of living systems with quantum enhanced precision. Naturally occurring lipid particles were tracked within the cytoplasm of Saccharomyces cerevisiae yeast cells, with squeezed light enhancing precision by 2.4 dB. The thermal motion of these particles could then be analyzed to infer the viscosity and elasticity of the local environment, with squeezed light allowing 64% faster observations, thus improving the sensitivity to dynamic biological changes. This experiment was then extended to spatially resolved quantum imaging, with lipid particles used as scanning probes in a technique called photonic force microscopy. The particles sample variations in the local environment with resolution limited by measurement precision rather than the diffraction limit. The use of squeezed light was found to enhance spatial resolution by 14% at an absolute resolution level of 10 nm, comparable to leading classical experiments. This was the first demonstration of both sub-diffraction limited resolution and quantum enhanced resolution in biology, and places practical applications of quantum imaging within reach. Finally, the future challenges and prospects of quantum enhanced particle tracking are outlined.n
Quantum-enhanced metrology techniques offer ultra-precise timekeeping, allowing for breakthroughs in navigation systems, global positioning, medical and Biological imaging. Quantum metrology, a core application of quantum technologies, leverages non-classical states of light (such as entanglement and squeezing) to enhance measurement precision, sensitivity, and resolution beyond the classical limits, particularly the shot-noise limit. Its application to bio imaging and microscopy offers significant advantages for studying delicate biological specimens, which are often susceptible to damage from the intense light typically required by conventional high-resolution methods. The abstract highlights the potential of quantum properties of light to revolutionize bio imaging by providing a non-invasive, highly sensitive, and high-resolution platform for observing biological processes at fundamental scales.
State-of-the-art microscopes use intense lasers that can severely disturb biological processes, function and viability. This introduces hard limits on performance that only quantum photon correlations can overcome. In this talk I will report recent work from my laboratory which demonstrates this absolute quantum advantage [1]. We show, specifically, that quantum correlations enable signal-to-noise beyond the photodamage-free capacity of conventional microscopy. Broadly, this represents the first demonstration that quantum correlations can allow sensing beyond the limits introduced by optical intrusion upon the measurement process. We achieve this in a coherent Raman microscope, which we use to image molecular bonds within a cell with both quantum-enhanced contrast and sub-wavelength resolution. This allows the observation of nanoscale biological structures that would otherwise not be resolved. Coherent Raman microscopes allow highly selective biomolecular finger-printing in unlabelled specimens, but photodamage is a major roadblock for many applications. By showing that this roadblock can be overcome, our work provides a path towards order-of-magnitude improvements in both sensitivity and imaging speed.
A study published in the international journal Biomedical Optics Express comprehensively demonstrates the potential of quantum imaging techniques using entangled photons to simultaneously achieve minimal invasiveness (non-destructiveness) and extreme precision when observing biological specimens. It argues that illuminating biological specimens with non-classical states of light, such as entangled photon pairs, can physically block uncorrelated classical background noise and exponentially improve the signal-to-noise ratio (SNR). By utilizing quantum correlations and squeezed light states, it transcends the diffraction limit of conventional optical systems, offering unprecedented resolution to visualize delicate biological structures in their natural state. [Quantum Biology Society] Achieving a perfect balance between minimal invasiveness and extreme precision in biological measurements has long been a challenge in the scientific community. Conventional classical optical imaging techniques required intense illumination to obtain high resolution, which inevitably led to cellular damage and ran into the barrier of physical diffraction limits. A recent study published in the international journal Biomedical Optics Express, titled "Application of quantum imaging in biology," comprehensively highlights how quantum imaging technology based on non-classical light breaks through these classical limitations. A joint research team consisting of Hoda Lotfipour, Hassan Sobhani, Mohamad Taghi Dejpasand, and Morteza Sasani Ghamsari from the Photonics and Quantum Technologies Research School at the Nuclear Science and Technology Research Institute (NSTRI) in Tehran, Iran, published this disruptive review study. ■ Quantum Entanglement Perfectly Blocking Noise The researchers focused on the potential of quantum metrology, which introduces non-classical states of light—particularly methods utilizing entangled photon pairs—into biological imaging. When extremely delicate and fragile biological specimens are illuminated with light in entangled quantum states, significant signals can be precisely sorted out through the strong quantum correlations between photons. Through this process, classical background noise that occurs randomly and independently of the entanglement state is physically blocked, ultimately leading to a remarkable, exponential improvement in the system's signal-to-noise ratio (SNR). ■ Extreme Resolution Without Destructive Sampling This innovative, non-invasive quantum microscopy technique opens the path to visualizing living organisms in their natural state without burning or damaging specimens with intense light energy. Furthermore, by actively exploiting quantum correlations and squeezed light states, it easily surpasses the diffraction limits and shot-noise limits of conventional microscopes, making it possible to observe the minute dynamics of intermolecular interactions. This study eloquently demonstrates that quantum imaging technology, which provides unprecedented ultra-high resolution without the risk of destructive sampling, is the core key that will fundamentally shift the paradigm of next-generation biology and precision medicine research. #QuantumImaging #BiologicalImaging #QuantumEntanglement #NonInvasiveImaging #QuantumMicroscopy #PhotonEntanglement #OvercomingNoiseLimits #QuantumBiology #Biophysics #KoreanQuantumBiologySociety https://pmc.ncbi.nlm.nih.gov/articles/PMC12339294/
Application of quantum imaging in biology In biology, one of the main challenges is achieving a balance between high precision and minimal invasiveness in measurements. With cutting-edge techniques, the primary limitations to experimental accuracy often stem not from device-related noise but from fundamental physical constraints. Since nature is the underlying source of these constraints, it makes sense to go to quantum mechanics, the most basic theory of matter, for a solution. Improved measurement performance may be possible through the application of quantum effects, particularly those pertaining to coherence. It offers useful tools that, at the very least, offer interesting technical solutions even when they don't fully display cohesive behaviors. One of the primary applications of quantum technologies is quantum metrology, which uses the non-classical state of light to measure physical properties with great resolution and sensitivity. For biological applications, the quantum state of light may be utilized for precision enhancement and quantum noise reduction. This explains how quantum metrology, and particularly quantum imaging, can be used to enhance picture quality, measure shifts in quantum scales in biological systems, and boost imaging precision and resolution using quantum light sources, devices, and protocols. In this study, we give a summary of the possible uses of quantum technology in biology and medicine. This review presents a comprehensive overview of how quantum technologies can be applied in biology and medicine. It also explores the latest developments in quantum biological imaging, quantum microscopy, and quantum materials, while discussing the challenges and opportunities these emerging technologies bring.
In optical microscopy, as in any biological measurement performed with light, there is a compromise between increasing power to improve resolution and decreasing power to prevent photodamage to the biological structure. Quantum optics allows this compromise to be overcome, enabling improved precision without increased illumination intensity. This thesis demonstrates, for the first time, absolute quantum advantage in microscopy, with a specific focus on Stimulated Raman Scattering (SRS) microscopy.SRS microscopy is a powerful tool widely used in many fields, especially in biomedical sciences. It uses a two-photon process where the light is downshifted in frequency by being absorbed and subsequently inelastically scattered by the intrinsic molecular vibrations in the sample. Each element or molecule has a different response, allowing selective imaging of biological systems. SRS microscopy is particularly useful because it is label-free (no addition of dyes, beads or any implanted tracer), meaning that imaging contrast is achieved without modification of, or interference with, the specimen. Here I present our newly built state-of-the-art shot-noise limited SRS microscope. I also characterize the Raman microscope, describe the developped imaging system and show SRS spectroscopy and imaging of both polystyrene beads and living yeast cells.The quantisation of light introduces a fundamental uncertainty, or quantum noise, in both the amplitude and phase quadratures of an optical field. A squeezed state of light is a state of the optical field where the uncertainty of one of these quadratures is reduced below the quantum noise. Therefore, it provides an approach to reduce the noise level below this quantum noise limit and consequently increases measured signal-to-noise ratio. Here I describe the concepts involved in this technique and present our newly built light squeezer. I characterize the squeezing and show up to -1.3 dB of noise floor reduction for a 6 picosecond pulsed laser, which is the pulse duration that maximises the Raman interaction.In this thesis we apply squeezed states of light in SRS, developping a quantum-enhanced micro- scope. Our SRS Raman intensity noise is ∆I/I ≈ 10^(−7) and the measured quantum efficiency of the built photodiode is η = 72%. In this proof of principle we show a reduction of the noise floor of at least 13% below the quantum noise limit for Raman imaging of polystyrene beads and living yeast cells. This enhancement allowed us to resolve the cell membrane where with conventional microscope would be unresolvable. It also allowed sub-micron spatial resolution. The improved image contrast and reduced imaging time, while avoiding photodamage in the sample, surpasses the current state-of-the-art Raman microscopes and opens opportunities for new discoveries in biophysics.