Two revolutions in quantum sensing are converging on the same microscope stage. Biological qubits have emerged as genetically encoded, optically addressable quantum systems inside live cells. Solid state spin based qubits have been entangled and used as nanoscale correlator magnetometers, delivering sensitivity and spatial-resolution gains that single-spin probes cannot reach. Here we report a pulsed quantum microscope that enables simultaneous quantum state manipulation of both qubit technologies in live cells. The platform combines nanosecond-gated optical excitation at 450 nm and 520 nm, three-dimensional diffraction-limited addressing by galvo beam scanning and piezo objective focus, rapidly switched static and radio-frequency magnetic fields, single-photon timing with picosecond resolution, and microwave control for frequencies from DC to 5 GHz, including the 2.87 GHz resonance of solid state spins, the 500 MHz to 800 MHz resonance of radical pairs in biological qubits, and any future qubit resonance in the GHz range. Live cell imaging with simultaneous biological and solid state nanoparticle qubits in the same cell demonstrates the power of this technique for multiplexed quantum sensing. We anticipate this approach will open new opportunities for researchers to explore quantum sensing in live cells, and, ultimately, entanglement between a solid-state qubit and a protein-hosted spin qubit.
Two revolutions in quantum sensing are converging on the same microscope stage. Biological qubits have emerged as genetically encoded, optically addressable quantum systems inside live cells. Solid state spin based qubits have been entangled and used as nanoscale correlator magnetometers, delivering sensitivity and spatial-resolution gains that single-spin probes cannot reach. Here we report a pulsed quantum microscope that enables simultaneous quantum state manipulation of both qubit technologies in live cells. The platform combines nanosecond-gated optical excitation at 450 nm and 520 nm, three-dimensional diffraction-limited addressing by galvo beam scanning and piezo objective focus, rapidly switched static and radio-frequency magnetic fields, single-photon timing with picosecond resolution, and microwave control for frequencies from DC to 5 GHz, including the 2.87 GHz resonance of solid state spins, the 500 MHz to 800 MHz resonance of radical pairs in biological qubits, and any future qubit resonance in the GHz range. Live cell imaging with simultaneous biological and solid state nanoparticle qubits in the same cell demonstrates the power of this technique for multiplexed quantum sensing. We anticipate this approach will open new opportunities for researchers to explore quantum sensing in live cells, and, ultimately, entanglement between a solid-state qubit and a protein-hosted spin qubit.
• Overcoming existing limitations of ultra-low temperatures and silicon bases by utilizing 3-nanometer (nm) fluorescent proteins as qubits. • Successful control of quantum states (Rabi oscillations) within E. coli at room temperature and human cells. • Enabling ultra-precise measurement of magnetic fields and temperatures inside cells... Heralding a paradigm shift in new drug development and cell imaging technologies. [Quantum Biology Society] The long-standing conventional wisdom that quantum technology can only be realized at cryogenic temperatures based on hard, highly ordered materials like diamonds or silicon has been broken. Biological quantum bits (qubits) that operate directly inside the watery and complex biological environment—that is, inside 'living cells'—have been developed for the first time in the world. Citing a study recently published in the international academic journal Nature, the US-based Science News reported that scientists have created biological qubits merely 3 nanometers (nm) in diameter using fluorescent proteins. ■ Controlling Quantum Mechanics with Biotechnology Tools Existing quantum technologies require extremely cold temperatures and strictly controlled environments, making them difficult to apply to unstable settings like the inside of living organisms. However, the research team chose to manipulate the spin of the 'fluorophore,' a specific part of a protein that emits light when exposed to it. Using genetic engineering, the research team directly produced this protein inside laboratory cells. They then succeeded in awakening the quantum properties of the protein by shooting laser light at it, fine-tuning it with microwaves, and observing the luminescence phenomenon. ■ Qubits Operating at 'Room Temperature'... Reading the Microenvironment of Diseases The most surprising achievement is the temperature of the experimental environment. Unlike the majority of qubits that lose their function at high temperatures, this biological qubit successfully demonstrated quantum state changes called 'Rabi oscillations' inside human cells at 175 Kelvin (-98.15°C), as well as inside E. coli at room temperature. This technological leap signifies the birth of 'biological quantum sensors' that can measure microscopic conditions such as magnetic fields and temperatures inside cells with unprecedented precision. It is expected to enable a new dimension of medical imaging technology and targeting by allowing the root causes of diseases to be identified at the intracellular molecular level. Amidst recent active academic movements in South Korea to integrate quantum mechanics into life phenomena, centered around the Quantum Biology Society, this study is also providing great inspiration for R&D strategies in the pharmaceutical and biotech industries. In particular, such quantum sensing technology, which can precisely target and measure the microenvironment inside cells, could become a powerful key to maximizing the value of innovative pipelines in the future. Fluorescent proteins, which have been used for decades in biology labs to track proteins and cancer cells, are now wearing the clothes of quantum mechanics and opening a new era of quantum biology.
Live-cell imaging of cellular and tissue samples relies predominantly on optical modalities, such as fluorescence, confocal, and multiphoton microscopy, in which cellular information is encoded in emitted photons. Photons scatter and attenuate in biological samples, restricting depth resolution, while the excitation light required to produce them induces photodamage that perturbs the very biology under observation. Magnetic fields, by contrast, traverse biological samples without attenuation at cellular length scales, but the imaging modality that extracts the encoded information, magnetic resonance imaging, cannot resolve individual cells. Here we present Quantum Cell Monitoring (QCM), a widefield nitrogen-vacancy magnetometry platform that encodes single-cell information in stray magnetic fields rather than emitted photons and reads it out at subcellular resolution. Integrated with a specialized live-cell incubator, QCM tracks magnetically labeled living cancer for up to 72 h through their individual magnetic field signatures. It captures single-cell mitosis and morphological remodeling, as well as cell cluster formation, splitting, and migration even within dense regions where brightfield contrast collapses. By shifting the carrier of single-cell information from propagating optical photons to static magnetic stray fields, QCM decouples cell from cellular optical accessibility and auto-fluorescence, enabling sustained live-cell observation in regimes inaccessible to optical microscopy.
InAs quantum dots (QDs) can be used as optically coupled quantum storage devices for quantum information applications. The QD can be charged with a single electron, where the spin state (up or down) provides a long lived quantum bit (qubit). The QD's optically excited states are used to initialize, manipulate, and read out the electron spin state with laser pulses. However, most practical quantum information applications require many interacting qubits, forming a quantum network. Since QDs are based on semiconductor technology, and are compatible with standard nano-fabrication processing, there is promise that they can provide a solid state platform where a scalable quantum information architecture is realizable. We focus on scaling the QD system to multiple qubits using intermediate spin-photon entangled states. In this work, experimental and theoretical techniques are developed to study the QD-light matter interaction at the single photon level. Resonance fluorescence from a single QD is experimentally realized, and the single photon nature of the scattered radiation is verified through intensity correlation experiments. Transient fluorescence measurements on resonantly excited QDs are performed using time correlated single photon counting techniques to measure the excited state lifetime. High speed electro-optic modulators are used to time gate narrow bandwidth lasers, so that a QD can be driven under step-wise excitation, allowing for the direct observation of time-dependent optical Rabi oscillations. From these measurements, we are able to extract a decoherence rate which is consistent with the lifetime limit, indicating that pure dephasing is negligible in this system. These techniques are applied to the QD spin system to demonstrate a spin-photon entangled state, by performing correlation measurements on the spin and photon state in two bases. A lower bound on the entanglement fidelity of 0.59(4) is achieved, which exceeds the classical limit of 0.5 by more than two standard deviations. The entanglement fidelity is limited primarily by the finite timing resolution of available single photon detectors. Taking this into account, we achieve 84% of the apparatus limited fidelity. These spin-entangled photons can be used to mediate entanglement between distant QD spins, providing the basis of an optically coupled QD spin network.
Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artifacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient detail to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science.
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.
Quantum sensing harnesses squeezing, entanglement, and quantum correlations to surpass classical measurement limits. This work highlights our efforts to extend measurement capabilities from microscopic biological systems to metropolitan-scale networks. At the microscopic level, we demonstrate squeezed-light–enhanced Brillouin microscopy for label-free probing of cellular mechanics, achieving higher imaging contrast with reduced photodamage and significantly improved viability in live cancer cells and brain tissue. At the macroscopic level, we report the first distribution of multi-photon entanglement across a deployed commercial fiber network in downtown Chattanooga, establishing heralded Bell and N00N states between distant network nodes. Together, these advances show that quantum optics can unify applications from microscopy to metro-scale networks, signaling a future where quantum optical sensing evolves into a widely deployed and scalable technology.