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Quantum Effects and Measurement Techniques in Biology and Biophotonics

Quantum-enhanced super-resolution bioimaging: breaking the diffraction barrier with entangled photons

Lihong V. Wang

Published Mar 4, 2026• 0 citations
Publisher

Abstract

Entangled photons enable quantum imaging to surpass classical limits in resolution and noise. To address long-standing challenges in quantum imaging (such as low signal-to-noise, limited resolvable pixels, and difficulty imaging biological samples), we present imaging by coincidence from entanglement (ICE). ICE leverages spatial and polarization entanglement to enhance resolution, support biological imaging, and quantify birefringence properties. Polarization entanglement enables remote, quantitative measurement of both phase retardation and principal axis orientation without changing input polarization. ICE achieves up to 25-fold stray light suppression relative to classical imaging. We further introduce wide-field quantum microscopy by coincidence (QMC) using symmetric, balanced paths to achieve Heisenberg-limited super-resolution, with up to 155-fold suppression of stray light and improved speed and contrast-to-noise ratio. Together, QMC and ICE represent significant advances in quantum bioimaging, offering low-light, high-resolution, and noninvasive imaging capabilities with potential impact in life sciences and remote sensing.

DOI
10.1117/12.3076000

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Entangled photons enable quantum imaging to surpass classical limits in resolution and noise. To address long-standing challenges in quantum imaging (such as low signal-to-noise, limited resolvable pixels, and difficulty imaging biological samples), we present imaging by coincidence from entanglement (ICE). ICE leverages spatial and polarization entanglement to enhance resolution, support biological imaging, and quantify birefringence properties. Polarization entanglement enables remote, quantitative measurement of both phase retardation and principal axis orientation without changing input polarization. ICE achieves up to 25-fold stray light suppression relative to classical imaging. We further introduce wide-field quantum microscopy by coincidence (QMC) using symmetric, balanced paths to achieve Heisenberg-limited super-resolution, with up to 155-fold suppression of stray light and improved speed and contrast-to-noise ratio. Together, QMC and ICE represent significant advances in quantum bioimaging, offering low-light, high-resolution, and noninvasive imaging capabilities with potential impact in life sciences and remote sensing.
Quantum imaging holds potential benefits over classical imaging but has faced challenges such as poor signal-to-noise ratios, low resolvable pixel counts, difficulty in imaging biological organisms, and inability to quantify full birefringence properties. Here, we introduce quantum imaging by coincidence from entanglement (ICE), using spatially and polarization-entangled photon pairs to overcome these challenges. With spatial entanglement, ICE offers higher signal-to-noise ratios, greater resolvable pixel counts, and the ability to image biological organisms. With polarization entanglement, ICE provides quantitative quantum birefringence imaging capability, where both the phase retardation and the principal refractive index axis angle of an object can be remotely and instantly quantified without changing the polarization states of the photons incident on the object. Furthermore, ICE enables 25 times greater suppression of stray light than classical imaging. ICE has the potential to pave the way for quantum imaging in diverse fields, such as life sciences and remote sensing.
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We introduce quantum microscopy by coincidence (QMC) featuring balanced pathlengths, which facilitates super-resolution imaging at the Heisenberg limit, drastically boosting speed and contrast-to-noise ratio (CNR) compared to existing wide-field quantum imaging methods. QMC uses correlated photons traversing symmetric paths, behaving like a photon with half the wavelength for twice the resolution. It withstands 155 times stronger stray light than classical signals, promising non-destructive bioimaging. Our approach propels quantum imaging to microscopic scale by imaging cancer cells. Experimental and theoretical results endorse this balanced pathlength configuration as a path to quantum-enhanced coincidence imaging at the Heisenberg limit.
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/
Technological advancements in the creation, manipulation and detection of quantum states of light have motivated the application of such states to overcome classical limits in sensing and imaging. In particular, there has been a surge of recent interest in super-resolution imaging based on principles of quantum optics. However, the application of such schemes for practical imaging of biological samples is demanding in terms of signal-to-noise ratio, speed of acquisition and robustness with respect to sample labeling. Here, we re-introduce the concept of quantum image scanning microscopy (Q-ISM), a super-resolution method that enhances the classical image scanning microscopy (ISM) method by measuring photon correlations. Q-ISM was already utilized to achieve super-resolved images of a biological sample labeled with fluorescent nanoscrystals whose contrast is based entirely on a quantum optical phenomenon, photon antibunching. We present here an experimental demonstration of the method and discuss with further details its prospects for application in life science microscopy.
Abstract Quantum entanglement is a powerful resource that revolutionizes information science, opens new horizons in communication technologies, and pushes the frontiers of sensing and imaging. Whether or not the methods of quantum entanglement can be extended to life-science imaging is far from clear. Live biological systems are eluding quantum-optical probes, proving, time and time again, too lossy, too noisy, too warm, and too wet to be meaningfully studied by quantum states of light. The central difficulty that puts the main roadblock on the path toward entanglement-enhanced nonlinear bioimaging is that the two-photon absorption (TPA) of entangled photons can exceed the TPA of uncorrelated photons only at the level of incident photon flux densities as low as one photon per entanglement area per entanglement time. This fundamental limitation has long been believed to rule out even a thinnest chance for a success of bioimaging with entangled photons. Here, we show that new approaches in nonlinear and quantum optics, combined with the latest achievements in biotechnologies, open the routes toward efficient photon-entanglement-based strategies in TPA microscopy that can help confront long-standing challenges in life-science imaging. Unleashing the full potential of this approach will require, however, high throughputs of virus-construct delivery, high expression efficiencies of genetically encodable fluorescent markers, high-brightness sources of entangled photons, as well as a thoughtful entanglement engineering in time, space, pulse, and polarization modes. We demonstrate that suitably tailored nonlinear optical fibers can deliver entangled photon pairs confined to entanglement volumes many orders of magnitude smaller than the entanglement volumes attainable through spontaneous parametric down-conversion. These ultracompact modes of entangled photons are shown to enable a radical enhancement of the TPA of entangled photons, opening new avenues for quantum entanglement in life-science imaging.