Quantum entanglement has been shown to imply correlations stronger than those allowed by classical models. The possibility of performing tasks that are classically impossible has made quantum entanglement a powerful resource for the development of novel methods and applications in various fields of research such as quantum computing, quantum cryptography, and quantum metrology. There is a great need for the development of next generation instrumentation and technologies utilizing entangled quantum light. Among the many applications of nonclassical states of light, nonlinear microscopy has the potential to make an impact in broad areas of science from physics to biology. Here, the microscopic image created by the fluorescence selectively excited by the process of the entangled two-photon absorption is reported. Entangled two-photon microscopy offers nonlinear imaging capabilities at an unprecedented low excitation intensity 10 7, which is 6 orders of magnitude lower than the excitation level for the classical two-photon image. The nonmonotonic dependence of the image on the femtosecond delay between the components of the entangled photon pair is demonstrated. This delay dependence is a result of specific quantum interference effects associated with the entanglement and this is not observable with classical excitation light. In combination with novel spectroscopic capabilities provided by a nonclassical light excitation, this is of critical importance for sensing and biological applications.
Quantum entanglement has been shown to imply correlations stronger than those allowed by classical models. The possibility of performing tasks that are classically impossible has made quantum entanglement a powerful resource for the development of novel methods and applications in various fields of research such as quantum computing, quantum cryptography, and quantum metrology. There is a great need for the development of next generation instrumentation and technologies utilizing entangled quantum light. Among the many applications of nonclassical states of light, nonlinear microscopy has the potential to make an impact in broad areas of science from physics to biology. Here, the microscopic image created by the fluorescence selectively excited by the process of the entangled two-photon absorption is reported. Entangled two-photon microscopy offers nonlinear imaging capabilities at an unprecedented low excitation intensity 10 7, which is 6 orders of magnitude lower than the excitation level for the classical two-photon image. The nonmonotonic dependence of the image on the femtosecond delay between the components of the entangled photon pair is demonstrated. This delay dependence is a result of specific quantum interference effects associated with the entanglement and this is not observable with classical excitation light. In combination with novel spectroscopic capabilities provided by a nonclassical light excitation, this is of critical importance for sensing and biological applications.
Correct biological interpretation from cell imaging can be achieved only if the observed phenomena proceed with negligible perturbation from the imaging system. Herein, we demonstrate microscopic images of breast cancer cells created by the fluorescence selectively excited in the process of entangled two-photon absorption in a scanning microscope at an excitation intensity orders of magnitude lower than that used for classical two-photon microscopy. Quantum enhanced entangled two-photon microscopy has shown cell imaging capabilities at an unprecedented low excitation intensity of ∼3.6 × 10 7 photons/s, which is a million times lower than the excitation level for the classical two-photon fluorescence image obtained in the same microscope. The extremely low light probe intensity demonstrated in entangled two-photon microscopy is of critical importance to minimize photobleaching during repetitive imaging and damage to cells in live-cell applications. This technology opens new avenues in cell investigations with light microscopy, such as enhanced selectivity and time–frequency resolution.
The application of quantum states of light such as entangled photons, for example, created by parametric down conversion, has experienced tremendous progress in the almost 40 years since their first experimental realization. Initially, they were employed in the investigation of the foundations of quantum physics, such as the violation of Bell's inequalities and studies of quantum entanglement. They later emerged as basic platforms for quantum communication protocols and, in the recent experiments on single-photon interactions, in photonic quantum computation. These applications aim at the controlled manipulation of the photonic degrees of freedom, and therefore rely on simple models of matter, where the analysis is simpler. Furthermore, quantum imaging with entangled light can achieve enhanced resolution, and quantum metrology can overcome the shot noise limit for classical light. This Account focuses on an entirely different emerging class of applications using quantum light as a powerful spectroscopic tool to reveal novel information about complex molecules. These applications utilize two appealing properties of quantum light: its distinct intensity fluctuations and its nonclassical bandwidth properties. These give rise to new and surprising behavior of nonlinear optical signals. Nonclassical intensity fluctuations can enhance nonlinear optical signals relative to linear absorption. For instance, the two-photon absorption of entangled photon pairs scales linearly (rather than quadratically) in the photon flux, just like a single photon absorption. This enables nonlinear quantum spectroscopy of photosensitive, for example, biological, samples at low light intensities. We will discuss how the two-photon absorption cross section becomes a function of the photonic quantum state, which can be manipulated by properties of the entangled photon pairs. In addition, the quantum correlations in entangled photon states further influence the nonlinear signals in a variety of ways. Apart from affecting the signal's scaling with intensity, they also constitute an entirely new approach to shaping and controlling excitation pathways in molecular aggregates in a way that cannot be achieved with shaped classical pulses. This is because between the two absorption events in entangled two-photon absorption, the light and material system are entangled. Classical constraints for the simultaneous time and frequency resolution can thus be circumvented, since the two are not Fourier conjugates. Here we review the simplest manifestation of quantum light spectroscopy, two-photon absorption spectroscopy with entangled photons. This will allow us to discuss exemplarily the impact of quantum properties of light on a nonlinear optical signal and explore the opportunities for future applications.
Conspectus The enhanced interest in quantum-related phenomena has provided new opportunities for chemists to push the limits of detection and analysis of chemical processes. As some have called this the second quantum revolution, a time has come to apply the rules learned from previous research in quantum phenomena toward new methods and technologies important to chemists. While there has been great interest recently in quantum information science (QIS), the quest to understand how nonclassical states of light interact with matter has been ongoing for more than two decades. Our entry into this field started around this time with the use of materials to produce nonclassical states of light. Here, the process of multiphoton absorption led to photon-number squeezed states of light, where the photon statistics are sub-Poissonian. In addition to the great interest in generating squeezed states of light, there was also interest in the formation of entangled states of light. While much of the effort is still in foundational physics, there are numerous new avenues as to how quantum entanglement can be applied to spectroscopy, imaging, and sensing. These opportunities could have a large impact on the chemical community for a broad spectrum of applications. In this Account, we discuss the use of entangled (or quantum) light for spectroscopy as well as applications in microscopy and interferometry. The potential benefits of the use of quantum light are discussed in detail. From the first experiments in porphyrin dendrimer systems by Dr. Dong-Ik Lee in our group to the measurements of the entangled two photon absorption cross sections of biological systems such as flavoproteins, the usefulness of entangled light for spectroscopy has been illustrated. These early measurements led the way to more advanced measurements of the unique characteristics of both entangled light and the entangled photon absorption cross-section, which provides new control knobs for manipulating excited states in molecules. The first reports of fluorescence-induced entangled processes were in organic chromophores where the entangled photon cross-section was measured. These results would later have widespread impact in applications such as entangled two-photon microscopy. From our design, construction and implementation of a quantum entangled photon excited microscope, important imaging capabilities were achieved at an unprecedented low excitation intensity of 10 7 photons/s, which is 6 orders of magnitude lower than the excitation level for the classical two-photon image. New reports have also illustrated an advantage of nonclassical light in Raman imaging as well. From a standpoint of more precise measurements, the use of entangled photons in quantum interferometry may offer new opportunities for chemistry research. Experiments that combine molecular spectroscopy and quantum interferometry, by utilizing the correlations of entangled photons in a Hong–Ou–Mandel (HOM) interferometer, have been carried out. The initial experiment showed that the HOM signal is sensitive to the presence of a resonant organic sample placed in one arm of the interferometer. In addition, parameters such as the dephasing time have been obtained with the opportunity for even more advanced phenomenology in the future.
Fluorescence microscopy has become integral to biological studies for the technique’s ability to elucidate structures of biomolecules for in-situ studies with high selectivity and specificity. Imaging of intrinsic indicators, such as fluorescent amino acids in proteins, provides important information, but can be challenging to accomplish. Current microscopy techniques that measure native fluorescence without the use of exogenous labels involve either direct UV excitation which is commonly non-localized and can be detrimental to the system, or multiphoton absorption which must be conducted at high intensities, therefore posing high risks of photodamage. As such, we seek to investigate an efficient way to gently excite native fluorescence in biological systems in a way that overcomes these limitations. Quantum entangled photon pairs generated via spontaneous parametric downconversion (SPDC), may be an alternative to conducting two-photon absorption (TPA) to excite fluorescence in amino acids without the high fluences currently used. These photon pairs are highly correlated in time. Thus, the arrival of one photon is simultaneously followed by the arrival of its sister photon. As a result, a molecule interacting with the photon pair should simultaneously absorb both photons, leading to a linear two-photon absorption rate, and the linearity of the two-photon process should dramatically reduce the light intensity necessary for TPA. Therefore, quantum entangled photon pairs offer the possibility of performing low intensity UV excitation using photons in the visible wavelength range. With this work, we generated and characterized entangled photons generated via SPDC, and investigated whether fluorescent amino acids can be excited, and the subsequent fluorescence induced with entangled two-photon absorption. Results show that much higher entangled two-photon rates than what are currently available are needed to measure significant signals with entangled two-photon excitation.
The harnessing of the nonclassical properties in photon pairs generated by the process of Spontaneous Parametric Down Conversion (SPDC) to enhance two-photon interactions has long intrigued researchers. Their use in light-matter interactions has been proven to improve efficiency either by increasing the rate of generation or by suppressing noise. Namely, the processes of Entangled Sum Frequency Generation (eSFG) and Entangled Two Photon Absorption (eTPA) have been shown to produce more photons when stimulated with entangled photons than the classical versions of the effects. This has only been effective so far at very low intensities, which, alongside the inability to reproduce previous experimental results, has caused debates about the usefulness of the effect. In the presented work, I aim to shed light on the topic by employing a carefully crafted source of entangled photon pairs to improve two-photon effects. I attempt to demonstrate, through a series of experiments, that the quantum enhancement can be observed at an order of magnitude higher than previously thought possible. To solidify the results, a direct comparison of the quantum effect was conducted by investigating the performance of the phenomenon when it is stimulated by classical radiation from a laser. Our results confirm a quantum improvement in a regime previously considered impossible, and they enabled us to examine the ramifications of the effect on imaging. By doing so, we consider real-life microscopy applications, and therefore, we can set limits to the effect.
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.