What is Quantum Optical Microscopy?

By Samudrapom DamReviewed by Susha Cheriyedath, M.Sc.Updated on Nov 12 2024

Quantum optical microscopy techniques exploit the quantum properties of light, like entanglement, to improve the contrast, sensitivity, or resolution of imaging. Quantum effects improve the microscope performance by providing new methods to image at difficult-to-reach wavelengths in conventional microscopy and new super-resolution techniques. Quantum optical microscopy could transform the understanding of sub-cellular life and play a crucial role in materials science.^1-3

Image Credit: Konstantin Kolosov/Shutterstock.com

Importance of Quantum Optical Microscopy

Quantum optical microscopy offers a quantum leap in imaging capabilities. By harnessing the power of quantum mechanics, it exceeds the limitations of traditional optical microscopy.^2,3

Despite the significant advances in optical microscopy, biological structures and dynamics remain beyond the reach of current microscopy techniques. Further advances in speed, resolution, and signal-to-noise are essential to observe them.³

In several cases, the microscope performance is limited by quantum effects, such as noise due to light quantization into photons/shot noise or low cross-section of multi-photon scattering in multi-photon microscopes.³

Although the optical microscopy performance improves with rising light intensities due to lower noise and stronger interactions with the specimen, biological samples are sensitive to light-introduced damages, including physical damage, local heating, and photochemical effects, which affect the specimen's function, viability, and growth.⁴

These limitations could be addressed by exploiting the features of quantum mechanics, such as entanglement and quantum correlations between photons.³ Quantum optical microscopy exploits specially engineered light sources like entangled photons containing quantum correlations between photons.^2,3

These correlations could increase the interaction cross-section and reduce the measurement noise, thus improving the signal strength. Quantum correlations allow photons to arrive more regularly at the detector used in a microscope instead of random arrival, which improves the detection sensitivity and measurement accuracy and suppresses the measurement noise.^1-3

Several microscopic imaging techniques use a multi-photon interaction-generated signal and depend on the statistical chance that the necessary photons exist in the sample simultaneously. Quantum correlations can eliminate this statistical uncertainty, significantly enhancing the signal strength.^1,5

Quantum Optical Microscopy Techniques

Entangled two-photon microscopy, quantum Brillouin microscopy, and quantum Raman microscopy are major quantum optical microscopy techniques.^5-7

Entangled Two-photon Microscopy: Entangled two-photon microscopy can be used for enhanced microscopic structure recognition and obtain unique information regarding biological samples.

This technique provides a breakthrough over the classical two-photon microscopy by providing high molecular selectivity and enabling the use of orders of magnitude lower excitation intensity, which makes detection much safer for biological samples.⁵

Additionally, a non-classical time–bandwidth property is another crucial advantage of broadband entangled photons over their classical counterparts. This property could spectrally resolve extremely complex spectra and maintain ultrafast time resolution simultaneously.⁵

Thus, entangled two-photon microscopy could resolve biologically relevant features of non-human and human live cells while limiting photodamage compared to conventional microscopy techniques.⁵

Quantum Raman Microscopy: Raman microscopy investigates the vibration of molecules in a sample to identify their chemical composition. This technique is an effective tool for understanding the biological specimens’ nature and characterizing materials.⁶

Quantum-enhanced Raman microscopes have been developed using gravitational wave detection to suppress the microscope noise floor of live-cell imaging. These microscopes enable quantum imaging that allows biological structure detection that photodamage makes inaccessible to existing microscopes.⁶

Quantum Brillouin Microscopy: The uniqueness of Brillouin microscopy is its ability to assess local viscoelastic properties of tissues and cells, which are crucial for understanding microscopic-level mechanical forces and interactions. For instance, the variations in brain tissues’ local mechanical properties are a good indicator of developing health complications like Alzheimer’s disease or traumatic brain injury.⁷

The shot-noise limit is a key challenge in conventional Brillouin spectroscopy, as this limit diminishes the contrast and decreases the accuracy of defining local viscosity and stiffness. Quantum-enhanced Brillouin microscopy using squeezed states of light improves the Brillouin hyperspectral images’ signal-to-noise ratio. Thus, this technique could obtain imaging with significantly higher imaging contrast.⁷

Recent Advances

Quantum-optical coherence tomography (QOCT) is an optical sectioning technique that leverages the quantum interference of entangled photon pairs in a Hong-Ou-Mandel interferometer. Yet, the technique's long required acquisition times, stemming from low photon-pair emission rates, limit its practical application.⁸

A paper recently published in Physical Review Applied proposed a full-field QOCT-based quantum optical coherence microscopy technique, which utilizes entangled collinear photon pairs in a Linnik interferometer designed to address the previous QOCT implementation’s limitations.⁸

In this setup, the signal photon was detected using an intensified charge-coupled device camera. In contrast, the idler photon was collected using a multimode fiber, resulting in full-field transverse reconstruction through a single axial acquisition sequence. Additionally, this setup allowed concurrent QOCT and OCT trace acquisition, the former with the benefit of quantum-conferred advantages and the latter with greater counts.⁸

In another recent study published in Optics Express, a quantum-enhanced Raman microscope using a bright squeezed single-beam was proposed to enable operation at the optimal efficiency of the stimulated Raman scattering (SRS) process. The increase in brightness led to multimode effects that degraded the squeezing level, which was partially addressed using spatial filtering.⁶

This quantum-enhanced SRS microscope was applied to biological samples, and quantum-enhanced multispectral imaging of living cells was demonstrated. The imaging speed of 100 × 100 pixels in 18 s allowed the resolution of cell organelles’ dynamics. Additionally, the signal-to-noise ratio realized was compatible with video-rate imaging, with the quantum correlations resulting in a 20 % improvement in imaging speed compared to shot noise-limited operation.⁶

In a work published in Nature Communications, quantum microscopy by coincidence (QMC) with balanced pathlengths was proposed, which allows super-resolution imaging at the Heisenberg limit with significantly higher contrast-to-noise ratios (CNRs) and speeds compared to existing wide-field quantum imaging methods.²

QMC leverages a configuration with balanced optical pathlengths, where an entangled photon pair traversing symmetric paths in two arms behaves like a single photon with half the wavelength, resulting in a two-fold improvement in resolution. Simultaneously, QMC resists stray light up to 155 times stronger than classical signals.²

In QMCs, the biphotons’ low intensity and entanglement features ensure non-destructive bioimaging. Thus, QMC could advance quantum imaging to the microscopic level with substantial CNR and speed improvements toward cancer cell bioimaging.²

Conclusion

In conclusion, quantum optical microscopy represents a significant advancement in imaging techniques by utilizing quantum properties of light, such as entanglement and quantum correlations. Key methods like entangled two-photon and quantum Raman microscopy transform biological and material science imaging by reducing photodamage, improving signal strength, and enabling imaging at previously inaccessible wavelengths.

Recent developments, such as QOCT and QMC, further push the boundaries of super-resolution and live-cell imaging. These advances offer promising applications in cancer research and materials science by providing higher resolution, faster speeds, and enhanced accuracy in the future.

References and Further Reading

1. Quantum Optical Microscope [Online] Available at https://afresearchlab.com/technology/quantum-optical-microscope/ (Accessed on 11 November 2024)
2. He, Z., Zhang, Y., Tong, X., Li, L., & Wang, L. V. (2023). Quantum microscopy of cells at the Heisenberg limit. Nature Communications, 14(1), 1-8. DOI: 10.1038/s41467-023-38191-4, https://www.nature.com/articles/s41467-023-38191-4
3. Bowen, W. P. et al. (2023). Quantum light microscopy. Contemporary Physics, 1-25. DOI:10.1080/00107514.2023.2292380, https://www.tandfonline.com/doi/abs/10.1080/00107514.2023.2292380
4. Mauranyapin, N. P., Terrasson, A., Bowen, W. P. (2022). Quantum biotechnology. Advanced Quantum Technologies, 5(9), 2100139.  DOI:10.1002/qute.202100139, https://onlinelibrary.wiley.com/doi/full/10.1002/qute.202100139
5. Varnavski, O., Goodson III, T. (2020). Two-photon fluorescence microscopy at extremely low excitation intensity: The power of quantum correlations. Journal of the American Chemical Society, 142(30), 12966-12975. DOI: 10.1021/jacs.0c01153, https://pubs.acs.org/doi/abs/10.1021/jacs.0c01153
6. Terrasson, A. et al. (2024). Fast biological imaging with quantum-enhanced Raman microscopy. Optics Express, 32(21), 36193-36206. DOI: 10.1364/OE.523956, https://opg.optica.org/oe/fulltext.cfm?uri=oe-32-21-36193&id=560056
7. Yakovlev, V. V. (2023). Quantum-enhanced Brillouin microscopy. Optical Elastography and Tissue Biomechanics X. DOI: 10.1117/12.2659492, https://www.spiedigitallibrary.org/conference-proceedings-of-spie/PC12381/PC1238106/Quantum-enhanced-Brillouin-microscopy/10.1117/12.2659492.short
8. Yepiz-Graciano, P. et al. (2022). Quantum optical coherence microscopy for bioimaging applications. Physical Review Applied, 18(3), 034060. DOI: 10.1103/PhysRevApplied.18.034060, https://journals.aps.org/prapplied/abstract/10.1103/PhysRevApplied.18.034060

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