Quantum microscopy of cells at the Heisenberg limit

Abstract

Entangled biphoton sources exhibit nonclassical characteristics and have been applied to imaging techniques such as ghost imaging, quantum holography, and quantum optical coherence tomography. The development of wide-field quantum imaging to date has been hindered by low spatial resolutions, speeds, and contrast-to-noise ratios (CNRs). Here, we present quantum microscopy by coincidence (QMC) with balanced pathlengths, which enables super-resolution imaging at the Heisenberg limit with substantially higher speeds and CNRs than existing wide-field quantum imaging methods. QMC benefits from a configuration with balanced pathlengths, where a pair of entangled photons traversing symmetric paths with balanced optical pathlengths in two arms behave like a single photon with half the wavelength, leading to a two-fold resolution improvement. Concurrently, QMC resists stray light up to 155 times stronger than classical signals. The low intensity and entanglement features of biphotons in QMC promise nondestructive bioimaging. QMC advances quantum imaging to the microscopic level with significant improvements in speed and CNR toward the bioimaging of cancer cells. We experimentally and theoretically prove that the configuration with balanced pathlengths illuminates an avenue for quantum-enhanced coincidence imaging at the Heisenberg limit.

Publication
Nature Communications, vol. 14, no. 2441, pp. 1-8
Yide Zhang
Yide Zhang
Incoming Assistant Professor of ECEE and BME

My long-term research goal is to pioneer optical imaging technologies that surpass current limits in speed, accuracy, and accessibility, advancing translational research. With a foundation in electrical engineering, particularly in biomedical imaging and optics, my PhD work at the University of Notre Dame focused on advancing multiphoton fluorescence lifetime imaging microscopy and super-resolution microscopy, significantly reducing image generation time and cost. I developed an analog signal processing method that enables real-time streaming of fluorescence intensity and lifetime data, and created the first Poisson-Gaussian denoising dataset to benchmark image denoising algorithms for high-quality, real-time applications in biomedical research. As a postdoc at the California Institute of Technology (Caltech), my research expanded to include pioneering photoacoustic imaging techniques, enabling noninvasive and rapid imaging of hemodynamics in humans. In the realm of quantum imaging, I developed innovative techniques utilizing spatial and polarization entangled photon pairs, overcoming challenges such as poor signal-to-noise ratios and low resolvable pixel counts. Additionally, I advanced ultrafast imaging methods for visualizing passive current flows in myelinated axons and electromagnetic pulses in dielectrics. My research is currently funded by the National Institutes of Health (NIH) K99/R00 Pathway to Independence Award. I will join the University of Colorado Boulder (CU Boulder) as an Assistant Professor of Electrical, Computer & Energy Engineering (ECEE) and Biomedical Engineering (BME) in May 2025.

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