Quantum Biology Breakthrough: Fluorescent Proteins as Quantum Sensors!

Quantum technologies are the hottest thing out there (okay, after AI).

It feels like there is a breakthrough every day, a broken record here, a speed-up there, and more stable qubits. But if you’re like me, you barely know what a qubit is.

So, what better way to learn than to see it applied to fluorescent proteins and biology? That’s where we go today!

This is a long one, I warn you.

Proteins Go Quantum

Quantum Tech: Applied (Quantum) Mechanics

Quantum tech is promising to revolutionize everything.

Quantum technologies use quantum mechanics for practical purposes. Now, big disclaimer here: I’m no quantum physicist. So, I did my best to learn, and everything that follows is my understanding. Don’t take it as gospel, and if you’re an expert, please correct me!

With that out of the way, let’s jump into quantum technologies (for biologists)!

The Quantum Revolution: Computing and Sensing

So, you might have heard of quantum computing, and today we’re talking about its cousin, quantum sensing.

Quantum computing and quantum sensing share the same foundation: quantum mechanics. They both use “quantum systems” (spins, atoms, ions, or photons) that can exist in multiple states at once (superpositions) and that can be correlated in ways that classical physics can’t explain (entangled).

I know, it’s hard to wrap your head around. But stick with me, it’s worth it!

Quantum Computing: Quantum States to Process Information

Quantum computing is a completely new way to process information.

Quantum computers use qubits (quantum bits) that can be both 0 and 1 simultaneously. By manipulating qubits, quantum computers can perform massively parallel computations. They could, in principle, solve problems that would take classical computers millions of years, like:

• Drug discovery

• Protein folding simulations

• Quantum chemistry

• Cryptography

And more! Hence the hype.

But quantum computing is still in its infancy, and researchers are working hard to solve the challenges. Quantum states are fragile, and noise or thermal fluctuations easily destroy them. Quantum computers typically work near absolute zero!

In short, quantum computing uses quantum mechanics to calculate.

Quantum Sensing: Quantum States to Measure

Instead of using qubits to calculate, quantum sensing uses them to measure.

Quantum sensors use qubits as nanoscale probes. A qubit’s state changes in response to its surroundings (magnetic or electric fields, temperature, pH), and by reading out those changes, we can measure the environment with crazy precision.

This could mean:

• Mapping magnetic fields in neurons

• Tracking chemical reactions in enzymes

• Measuring nanoscale changes inside cells

Quantum sensors could even detect changes in single molecules or electrons inside cells! But we are not there yet.

In short, quantum sensing uses quantum mechanics to measure.

Qubits and Spins

So, qubits sit in the center of quantum sensing and computing. But what are they?

A qubit is not one specific physical thing. It’s a state. And it can be realized in different systems, if they obey quantum mechanics!

One common example is the spin state of an electron or a nucleus. Now, this is not an actual spin, like a ball. I know, confusing. It’s an intrinsic property of a particle, like charge or mass.

You can compare it to a sort of quantum “compass needle” that particles have.

This spin can “point” up or down, but also point up and down, thanks to superposition. That’s why it can be used as a qubit!

Just like real-life compasses, spin interacts with magnetic fields (still just an analogy! Spin is not a compass). A magnetic field can “tilt” or “flip” the spin, and the spin can generate a magnetic field of its own. And it can be used to measure magnetic fields!

By detecting how the spin state shifts, we can sense changes in the environment, at the level of single molecules or ions. This is how spin is used in quantum sensing and computing!

Connecting Quantum and Bio via Fluorescence

Okay, we’re finally ready to jump into today’s paper!

The team showed that EYFP (enhanced yellow fluorescent protein) can act as a spin qubit.

And it can be manipulated, read with light, and used as a nanoscale sensor!

But why fluorescent proteins?

Well, quantum sensing is not a thing in biology, because current approaches are not great. Nitrogen-vacancy centers in diamond or quantum dots have been used to map nanoscale magnetic events in cells, but efficient delivery and targeting are challenging! Plus, some of them are toxic to cells.

What if instead we could use biomolecules? Scientists have a bag full of small, fluorescent proteins, which can be genetically encoded to co-express with a protein of interest, fixing the delivery and targeting issue.

Fluorescent proteins could be molecular-scale quantum sensors, produced by the cell itself!

Inside a Fluorescent Qubit

EYFP’s fluorophore sits inside a β-barrel and absorbs light at 488 nm. When light hits the protein, the fluorophore goes from the ground state (S0) to an excited singlet state (S1). Normally, the fluorophore relaxes and goes from S1 to S0, releasing energy as photons (the fluorescence!).

But sometimes the fluorophore gets “stuck” in a different configuration, a somewhat stable triplet state.

And this triplet state (T1) is the qubit!

Its spin sublevels respond to microwave and weak magnetic fields. They are slightly different in energy, and the team developed an optical way to read these differences using delayed fluorescence. Basically, the protein emits light after a delay, which depends on the spin state!

How to Read a Spin: the OADF Trick

This readout method is called optically activated delayed fluorescence (OADF). In contrast with standard fluorescence, the light emission occurs with a delay, which frees it from the cellular autofluorescence background!

But they had to be smart to use it.

The T1 state is relatively stable, with a lifetime of milliseconds (“relatively” doing some heavy lifting here). This creates problems and limits the sensitivity, but the team found a cool trick to work around it!

They used a two-step setup:

1. Initialize the system with 488 nm, creating the stable triplet T1 state. The fluorophore can go back to S0 from here, but it takes time.

2. Pulse with a 912 nm light. This pushes the fluorophore from T1 to a less stable state T2, which returns to S0 rapidly and produces delayed fluorescence. The timing of the delayed fluorescence depends on the spin at state T1, so by measuring the fluorescence, you know the T1 spin!

And voilà, a working qubit using a fluorescent protein!

The team manipulated the qubit with microwaves and performed lots of experiments to prove it works! But since I don’t completely understand them, I’ll skip them.

But there is another cool part!

Qubits Inside Cells

The cool thing about proteins? Cells produce them.

So, the team made the qubit work inside cells! They tested 2 systems:

• HEK cells: They expressed EYFP and checked the proper cellular localization. Then, they plunged the cells at 175 K (-98°C!) and demonstrated that the qubits sense tiny changes in magnetic fields in situ.

• E. coli: They also expressed EYFP in bacteria, but they didn’t measure at low temperature as usual. They did the experiments at room temperature! And the qubit was acting as a super-sensitive intracellular sensor for magnetic fields.

Quantum Sensing, Coming Soon to a Cell Near You

A crazy work!

This wasn’t an easy paper to read and summarize for me, not gonna lie. But it’s crazy! And it’s so fascinating. I love reading about cutting-edge research like this! Although my brain might need to rest for a few days.

Quantum sensing has incredible potential, and adding protein in the mix makes it better:

• Quantum sensors are ridiculously sensitive. In theory, you can detect changes in the state of single electrons! Imagine following enzyme dynamics in real time!

• Proteins bring genetic tagging to quantum sensing, adding a dimension to it. Imagine sending proteins to the mitochondria to follow cellular respiration!

• The spin could be used as an "additional” color beyond the emission of the fluorescent protein, with potential for huge multiplexing.

Of course, none of this is close. There is a never-ending list of limitations for the current setup, with some being:

• Stability

• Temperature dependence

• Limited sensitivity

And more. But ehi, it’s a first-of-a-kind system! Of course it won’t work great out of the box. And it’s a super exciting direction! I’m pumped.

And if you need more details, go here and read the paper. It’s great!

If you made it this far, thank you! Do you see a future for quantum sensing in biology? Do you think we should stick to classical physics? Or should we make quantum computers with cells? Reply and let me know!

More Room:

• Rolling New Building Blocks: Rolling circle amplification (RCA) is a cool method to produce DNA. This study expands DNA amplification to include unnatural base pairs (UBPs), synthetic nucleotides that extend the natural genetic alphabet and increase DNA’s information capacity. The researchers showed that phi29 DNA polymerase can efficiently and accurately replicate a representative UBP (dNaM–dTPT3) and its analogues. They developed ExRCA (expanded rolling circle amplification), an isothermal method to mass-produce single- and double-stranded DNAs containing UBPs. These UBPs were then used to create site-specifically labeled DNA nanostructures, with additional applications in biomolecule detection, programmable DNA materials, and DNA-based catalysts.

• Securing DNA Nanostructures: Next time you log into your laptop, you could be using DNA origami. Okay, maybe not soon, but this study introduces a DNA-based data management system that enables hierarchical access control to molecularly encoded information. Using reconfigurable DNA nanostructures, the system employs two types of molecular “keys”: a polymerase trigger acting as a universal administrator key and DNA strand sets serving as specific user keys. These triggers induce conformational changes in the DNA carrier, converting hidden binding sites into readable data. Demonstrations showed that the admin key unlocked all stored data, while user keys granted selective access. This work establishes a framework for secure, multi-level data access in DNA information systems, paving the way for advanced molecular encryption and privacy management.

• More Rigid DNA Origami: I studied the rigidity of DNA origami in my PhD! I think it’s cool. Now, this study presents a rigidified double-layer DNA origami platform that improves the accuracy of surface-confined DNA computing. Traditional single-layer DNA origami circuits suffer from signal leakage due to structural fluctuations, causing unwanted molecular crosstalk. By reinforcing the origami into a stiffer, double-layer design, the researchers minimized these fluctuations, resulting in higher-fidelity signal transmission and enhanced on–off ratios. The platform successfully implemented parallel circuits and logic gates with improved performance, offering a general strategy for building reliable, high-precision DNA computing systems.

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