A new optically addressable quantum bit (qubit) encoded in a fluorescent protein could be used as a sensor that can be directly produced inside living cells. The device opens up a new era for fluorescence microscopy to monitor biological processes, say the researchers at the University of Chicago Pritzker School of Molecular Engineering who designed the novel qubit.

Quantum technologies use qubits to store and process information. Unlike classical bits, which can exist in only two states, qubits can exist in a superposition of both these states. This means that computers employing these qubits can simultaneously process multiple streams of information, allowing them to solve problems that would take classical computers years to process.

Qubits can be manipulated and measured with high precision, and in quantum sensing applications they act as nanoscale probes whose quantum state can be initialized, coherently controlled and read out. This allows them to detect minute changes in their environment with exquisite sensitivity.

Optically addressable qubit sensors – that is, those that are read out using light pulses from a laser or other light source – are able to measure nanoscale magnetic fields, electric fields and temperature. Such devices are now routinely employed by researchers working in the physical sciences. However, their use in the life sciences is lagging behind, with most applications still at the proof-of-concept stage.

Difficult to position inside living cells

Many of today’s quantum sensors are based on nitrogen-vacancy (NV) centres, which are crystallographic defects in diamond. These centres occur when two neighbouring carbon atoms in diamond are replaced by a nitrogen atom and an empty lattice site and they act like tiny quantum magnets with different spins. When excited with laser pulses, the fluorescent signal that they emit can be used to monitor slight changes in the magnetic properties of a nearby sample of material. This is because the intensity of the emitted NV centre signal changes with the local magnetic field.

“The problem is that such sensors are difficult to position at well-defined sites inside living cells,” explains Peter Maurer, who co-led this new study together with David Awschalom. “And the fact that they are typically ten times larger than most proteins further restricts their applicability,” he adds.

“So, rather than taking a conventional quantum sensor and trying to camouflage it to enter a biological system, we therefore wanted to explore the idea of using a biological system itself and developing it into a qubit,” says Awschalom.

Fluorescent proteins, which are just 3 nm in diameter, could come into their own here as they can be genetically encoded, allowing cells to produce these sensors directly at the desired location with atomic precision. Indeed, fluorescent proteins have become the “gold standard” in cell biology thanks to this unique ability, says Maurer. And decades of biochemistry research has allowed researchers to generate a vast library of such fluorescent proteins that can be tagged to thousands of different types of biological targets.

“We recognized that these proteins possess optical and spin properties that are strikingly similar to those of qubits formed by crystallographic defects in diamond – namely that they have a metastable triplet state,” explain Awschalom and Maurer. “Building on this insight, we combined techniques from fluorescence microscopy with methods of quantum control to encode and manipulate protein-based qubits.”

In their work, which is detailed in Nature, the researchers used a near-infrared laser pulse to optically address a yellow fluorescent protein known as EYFP and read out its triplet spin state with up to 20% “spin contrast” – measured using optically detected magnetic resonance (ODMR) spectroscopy.

To test the technique, the team genetically modified the protein so that it was expressed in human embryonic kidney cells and Escherichia coli (E. coli) cells. The measured OMDR signals exhibited a contrast of up to 8%. While this performance is not as good as that of NV quantum sensors, the fluorescent proteins open the door to magnetic resonance measurements directly inside living cells – something that NV centres cannot do, says Maurer. “They could thus transform medical and biochemical studies by probing protein folding, monitoring redox states or detecting drug binding at the molecular scale,” he tells Physics World.

“A new dimension for fluorescence microscopy”

Beyond sensing, the unique quantum resonance “signatures” offer a new dimension for fluorescence microscopy, paving the way for highly multiplexed imaging far beyond today’s colour palette, Awschalom adds. Looking further ahead, using arrays of such protein qubits could even allow researchers to explore many-body quantum effects within biologically assembled structures.

Maurer, Awschalom and colleagues say they are now busy trying to improve the stability and sensitivity of their protein-based qubits through protein engineering via “directed evolution” – similar to the way that fluorescent proteins were optimized for microscopy.

“Another goal is to achieve single-molecule detection, enabling readout of the quantum state of individual protein qubits inside cells,” they reveal. “We also aim to expand the palette of available qubits by exploring new fluorescent proteins with improved spin properties and to develop sensing protocols capable of detecting nuclear magnetic resonance signals from nearby biomolecules, potentially revealing structural changes and biochemical modifications at the nanoscale.”

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Quantum computers open the door to profound increases in computational power, but the quantum states they rely on are fragile. Topologically protected quantum states are more robust, but the most experimentally promising route to topological quantum computing limits the calculations these states can perform. Now, however, a team of mathematicians and physicists in the US has found a way around this barrier. By exploiting a previously neglected aspect of topological quantum field theory, the team showed that these states can be much more broadly useful for quantum computation than was previously believed.

The quantum bits (qubits) in topological quantum computers are based on particle-like knots, or vortices, in the sea of electrons washing through a material. In two-dimensional materials, the behaviour of these quasiparticles diverges from that of everyday bosons and fermions, earning them the name of anyons (from “any”). The advantage of anyon-based quantum computing is that the only thing that can change the state of anyons is moving them around in relation to each other – a process called “braiding” that alters their relative topology.

However, as team leader Aaron Lauda of the University of Southern California explains, not all anyons are up to the task. Certain anyons derived from mathematical symmetries appear to have a quantum dimension of zero, meaning that they cannot be manipulated in quantum computations. Traditionally, he says, “you just throw those things away”.

The problem is that in this so-called “semisimple” model, braiding the remaining anyons, which are known as Ising anyons, only lends itself to a limited range of computational logic gates. These gates are called Clifford gates, and they can be efficiently simulated by classical computers, which reduces their usefulness for truly ground-breaking quantum machines.

New mathematical tools for anyons

Lauda’s interest in this problem was piqued when he realized that there had been some progress in the mathematical tools that apply to anyons. Notably, in 2011, Nathan Geer at Utah State University and Jonathan Kujawa at Oklahoma University in the US, together with Bertrand Patureau-Mirand at Université de Bretagne-Sud in France showed that what appear to be zero-dimensional objects in topological quantum field theory (TQFT) can actually be manipulated in ways that were not previously thought possible.

“What excites us is that these new TQFTs can be more powerful and possess properties not present in the traditional setting,” says Geer, who was not involved in the latest work.

As Lauda explains it, this new approach to TQFT led to “a different way to measure the contribution” of the anyons that the semisimple model leaves out – and surprisingly, the result wasn’t zero. Better still, he and his colleagues found that when certain types of discarded anyons – which they call “neglectons” because they were neglected in previous approaches – are added back into the model, Ising anyons can be braided around them in such a way as to allow any quantum computation.

The role of unitarity

Here, the catch was that including neglectons meant that the new model lacked a property known as unitarity. This is essential in the widely held probabilistic interpretation of quantum mechanics. “Most physicists start to get squeamish when you have, like, ‘non-unitarity’ or what we say, non positive definite [objects],” Lauda explains.

The team solved this problem with some ingenious workarounds created by Lauda’s PhD student, Filippo Iulianelli. Thanks to these workarounds, the team was able to confine the computational space to only those regions where anyon transformations work out as unitary.

Shawn Cui, who was not involved in this work, but whose research at Purdue University, US, centres around topological quantum field theory and quantum computation, describes the research by Lauda and colleagues as “a substantial theoretical advance with important implications for overcoming limitations of semisimple models”. However, he adds that realizing this progress in experimental terms “remains a long-term goal”.

For his part, Lauda points out that there are good precedents for particles being discovered after mathematical principles of symmetry were used to predict their existence. Murray Gell-Man’s prediction of the omega minus baryon in 1962 is, he says, a case in point. “One of the things I would say now is we already have systems where we’re seeing Ising anyons,” Lauda says. “We should be looking also for these neglectons in those settings.”

The research is published in Nature Communications.

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