⚛️ quantum physics

A Pulsed Live-Cell Quantum Microscope for Entangled Solid State and Biological Qubits

This paper presents a pulsed live-cell quantum microscope capable of simultaneously manipulating and sensing both genetically encoded biological qubits and entangled solid-state spin qubits within the same cell, thereby enabling multiplexed quantum sensing and paving the way for exploring entanglement between these distinct quantum systems.

Original authors: Javier Noé Ramos-Silva, Sangjun Noh, Minghao Jiang, Parisa Aghaei, Ayla Hazrathosseini, Jocelyn Leon, Philip Hemmer, Peter J. Burke

Published 2026-07-07

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CC BY 4.0

Original authors: Javier Noé Ramos-Silva, Sangjun Noh, Minghao Jiang, Parisa Aghaei, Ayla Hazrathosseini, Jocelyn Leon, Philip Hemmer, Peter J. Burke

Original paper licensed under CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine a high-tech microscope that doesn't just take pictures of cells, but actually "talks" to the tiny quantum particles inside them. This paper describes the creation of a new kind of microscope designed to do two very different jobs at the same time, like a conductor leading two different orchestras simultaneously.

Here is the breakdown of what they built and what they achieved, using simple analogies:

The Two "Musicians" (The Qubits)

The microscope is designed to control two types of tiny quantum "switches" (called qubits) that act like sensors:

The Solid-State Qubit (The Diamond Rock): These are tiny defects inside diamonds (specifically Nitrogen-Vacancy centers). Think of them as tiny, super-stable compass needles made of rock. They are great at sensing magnetic fields but are usually stuck outside the cell.
The Biological Qubit (The Living Protein): These are special proteins inside living cells (like MagLOV) that have been genetically engineered to act like quantum sensors. Think of them as tiny, living flashlights that change their brightness based on magnetic fields.

The Problem: Two Different Languages

Until now, scientists had microscopes that could talk to the "Diamond Rocks" or the "Living Proteins," but not both at the same time.

The Diamond Rocks need green light and high-frequency radio waves (microwaves) to be controlled.
The Living Proteins need blue light and lower-frequency radio waves to be controlled.

Trying to use one microscope for both was like trying to play a piano and a drum set at the exact same time with the same pair of hands—it was too complicated to manage.

The Solution: The "Pulsed Quantum Microscope"

The team built a new microscope that acts like a master conductor. It can switch between these two "languages" incredibly fast, allowing it to control both types of sensors inside the same living cell at the same time.

How it works (The Analogy):
Imagine a camera that can take a photo in split-second bursts (pulsing) rather than a steady stream of light.

The Light: It uses lasers that flash on and off in nanoseconds (billionths of a second). It can flash green (for the diamond) and blue (for the protein) with perfect timing.
The Radio: It has a special antenna (a loop under the petri dish) that can blast different radio frequencies. It can send high-pitched radio waves (2.8 GHz) to the diamond and lower-pitched waves (500–800 MHz) to the protein.
The Movement: Instead of moving the heavy microscope stage back and forth (which would shake the delicate cells), the microscope keeps the sample perfectly still. It uses fast-moving mirrors (galvo mirrors) to steer the laser beam around the cell, like a laser pointer dancing across a wall.

What They Actually Did (The Results)

The paper reports on building this machine and proving it works. They didn't just build it; they tested it with four specific achievements:

Finding the Diamond: They used the microscope to find a single "diamond rock" sensor embedded in a piece of diamond. They proved they could read its magnetic "compass" using green light and radio waves.
Measuring the Protein: They switched the settings to look at living human cells (HeLa cells) containing the special "living protein" sensors. They proved the microscope could see these proteins clearly.
The "Live" Test: They took living cells, stained them with a dye to see their structure, and proved the microscope could image them without killing them.
The Big Win (Simultaneous Imaging): This is the main claim. They put the "diamond rocks" (nanodiamonds) and the "living proteins" (MagLOV) into the same living cell. They turned on the microscope and successfully imaged both types of sensors at the exact same time.

Why This Matters (According to the Paper)

The authors say this is the first time a single machine has been able to handle both of these very different quantum systems in a live cell.

They describe this as a "holy grail" step toward a future experiment where they might try to "entangle" (link) a diamond sensor with a protein sensor. Imagine linking a rock from the outside world with a living part of a cell so they share a single quantum state. The paper says this specific microscope is the first tool built that is capable of attempting that experiment.

In short: They built a versatile, high-speed microscope that can juggle two different types of quantum sensors inside a living cell, proving that we can now study both "rock" and "protein" quantum physics in the same biological environment.

Technical Summary: A Pulsed Live-Cell Quantum Microscope for Entangled Solid State and Biological Qubits

Problem Statement
The field of quantum sensing is currently defined by two parallel advancements: the maturation of solid-state spin qubits (specifically Nitrogen-Vacancy (NV) centers in diamond) and the emergence of genetically encoded biological qubits (such as spin-correlated radical pairs in proteins like MagLOV). While solid-state qubits have recently demonstrated the ability to utilize entanglement for enhanced sensitivity and spatial resolution, these experiments have been confined to engineered diamond substrates. Conversely, biological qubit research has largely relied on continuous-wave (CW) detection, which suffers from steady-state limitations and lacks the time resolution necessary to probe fast radical-pair dynamics. A critical gap exists in the literature: there is no existing platform capable of simultaneously manipulating and reading out both solid-state and biological qubits within the same live-cell environment using pulsed protocols. This limitation hinders the potential for hybrid quantum sensing and the exploration of entanglement across the solid-state–biological boundary.

Methodology
The authors designed and implemented a pulsed quantum microscope based on a stationary-sample, inverted confocal architecture (Olympus IX71). The system integrates three core subsystems:

Optical Setup: The microscope utilizes a dual-excitation path combining a 520 nm laser (for NV centers) and a 450 nm laser (for biological qubits). These beams are combined via a dichroic mirror and routed through a galvo-galvo scanner. The optical path employs four nested $4f$ imaging systems to ensure that beam scanning does not alter the beam size or position on the objective's back aperture, maintaining diffraction-limited performance.
- Pulsing: To achieve nanosecond-gated excitation, the authors compared Acousto-Optic Modulators (AOMs) against electronic modulation of the laser diode current. They implemented a custom, open-source electronic driver for the fiber-coupled lasers, which offers high extinction ratios and cost-effectiveness compared to commercial AOMs.
- Detection: Fluorescence is descanned, spatially filtered by a confocal pinhole, and detected by a single-photon avalanche diode (SPD) with picosecond timing resolution using a Swabian Time Tagger 20.
Microwave and RF Control: The system delivers magnetic fields via a modular antenna setup.
- Solid-State Control: A broadband PCB loop antenna (compatible with petri dishes) delivers microwave pulses from DC to 5 GHz, covering the 2.87 GHz resonance of NV centers.
- Biological Control: The same antenna supports lower frequencies (500–800 MHz) required for the radio-frequency driven magnetic resonance (RYDMR) of biological qubits like MagLOV.
- Control Electronics: Microwave pulsing is synchronized with optical excitation and photon detection using a Swabian Pulse Streamer 8/2. The authors also demonstrate an alternative FPGA-based solution (RFSoC) for arbitrary waveform generation.
Software: A custom Python-based GUI (built on Napari) controls the galvo scanners, DAQ, and timing hardware, enabling real-time imaging, photon counting, and automated $z$ -stack optimization.

Key Contributions
The paper reports four specific technical contributions:

Architectural Integration: The demonstration of a stationary-sample, galvo-galvo inverted microscope that supports both green-excitation/red-collection protocols for NV centers and blue-excitation/RF-driven protocols for biological qubits on a single optical bench.
Solid-State Benchmarking: Validation of the platform using an implanted diamond plate, achieving single-NV optically detected magnetic resonance (ODMR) near 2.87 GHz and measuring a spin relaxation time ( $T_1$ ) of approximately 1.3 ms under ambient conditions.
Biological Compatibility: Successful confocal imaging of live HeLa cells stained with TMRE and cells expressing the genetically encoded MagLOV protein, demonstrating that the optical path can be reconfigured for biological fluorescence with minimal changes.
Simultaneous Live-Cell Imaging: The first demonstration of simultaneous imaging of biological qubits (MagLOV-expressing HeLa cells) and solid-state qubits (nanodiamonds internalized via endocytosis) within the same cell.

Results

NV Characterization: The system achieved a lateral resolution of ~300 nm (FWHM), consistent with the diffraction limit for 520 nm excitation. CW ODMR spectra showed a clear resonance dip at 2.87 GHz with ~1% contrast. Pulsed $T_1$ measurements yielded a relaxation time of $1.29 \pm 0.3$ ms.
Biological Imaging: The platform successfully resolved cellular morphology and mitochondrial fluorescence in TMRE-stained cells and MagLOV-expressing cells.
Hybrid Imaging: Confocal images confirmed the co-localization of nanodiamonds and MagLOV-expressing HeLa cells, proving the system's ability to address both qubit types simultaneously in a live-cell environment.

Significance and Claims
The authors claim that this work establishes the necessary microscope-level infrastructure to pursue three converging research trajectories:

Advanced Solid-State Sensing: The platform is architecturally positioned to support entangled NV-pair sensing protocols (e.g., Bell states and decoherence-free subspaces) previously demonstrated only on static substrates, now potentially applicable to biological environments.
Pulsed Biological Sensing: The transition from CW to pulsed operation enables time-resolved RYDMR and pump–field–probe spectroscopy for biological qubits, overcoming the steady-state limitations of current methods.
Hybrid Quantum Interfaces: Most significantly, the authors posit that this instrument provides the first credible experimental path to creating and measuring entanglement between a solid-state NV qubit and a biological spin qubit. They describe this hybrid entanglement as the "true holy grail of the quantum interface with biology," merging the long coherence of NV centers with the genetic targetability of protein-hosted qubits.

The paper concludes modestly, noting that while the current results validate the hardware and optical compatibility, the ultimate goal of demonstrating hybrid entanglement remains a future objective enabled by this new platform.