Light has always played a central role in healthcare, enabling a wide range of tools and techniques for diagnosing and treating disease. Nick Stone from the University of Exeter is a pioneer in this field, working with technologies ranging from laser-based cancer therapies to innovative spectroscopy-based diagnostics. Stone was recently awarded the Institute of Physics’ Rosalind Franklin Medal and Prize for developing novel Raman spectroscopic tools for rapid in vivo cancer diagnosis and monitoring. Physics World’s Tami Freeman spoke with Stone about his latest research.

What is Raman spectroscopy and how does it work?

Think about how we see the sky. It is blue due to elastic (specifically Rayleigh) scattering – when an incident photon scatters off a particle without losing any energy. But in about one in a million events, photons interacting with molecules in the atmosphere will be inelastically scattered. This changes the energy of the photon as some of it is taken by the molecule to make it vibrate.

If you shine laser light on a molecule and cause it to vibrate, the photon that is scattered from that molecule will be shifted in energy by a specific amount relating to the molecule’s vibrational mode. Measuring the wavelength of this inelastically scattered light reveals which molecule it was scattered from. This is Raman spectroscopy.

Because most of the time we’re working at room or body temperatures, most of what we observe is Stokes Raman scattering, in which the laser photons lose energy to the molecules. But if a molecule is already vibrating in an excited state (at higher temperature), it can give up energy and shift the laser photon to a higher energy. This anti-Stokes spectrum is much weaker, but can be very useful – as I’ll come back to later.

How are you using Raman spectroscopy for cancer diagnosis?

A cell in the body is basically a nucleus: one set of molecules, surrounded by the cytoplasm: another set of molecules. These molecules change subtlety depending on the phenotype [set of observable characteristics] of the particular cell. If you have a genetic mutation, which is what drives cancer, the cell tends to change its relative expression of proteins, nucleic acids, glycogen and so on.

We can probe these molecules with light, and therefore determine their molecular composition. Cancer diagnostics involves identifying minute changes between the different compositions. Most of our work has been in tissues, but it can also be done in biofluids such as tears, blood plasma or sweat. You build up a molecular fingerprint of the tissue or cell of interest, and then you can compare those fingerprints to identify the disease.

We tend to perform measurements under a microscope and, because Raman scattering is a relatively weak effect, this requires good optical systems. We’re trying to use a single wavelength of light to probe molecules of interest and look for wavelengths that are shifted from that of the laser illumination. Technology improvements have provided holographic filters that remove the incident laser wavelength readily, and less complex systems that enable rapid measurements.

Raman spectroscopy can classify tissue samples removed in cancer surgery, for example. But can you use it to detect cancer without having to remove tissue from the patient?

Absolutely, we’ve developed probes that fit inside an endoscope for diagnosing oesophageal cancer.

Earlier in my career I worked on photodynamic therapy. We would look inside the oesophagus with an endoscope to find disease, then give the patient a phototoxic drug that would target the diseased cells. Shining light on the drug causes it to generate singlet oxygen that kills the cancer cells. But I realized that the light we were using could also be used for diagnosis.

Currently, to find this invisible disease, you have to take many, many biopsies. But our in vivo probes allow us to measure the molecular composition of the oesophageal lining using Raman spectroscopy, to be and determine where to take biopsies from. Oesophageal cancer has a really bad outcome once it’s diagnosed symptomatically, but if you can find the disease early you can deliver effective treatments. That’s what we’re trying to do.

The very weak Raman signal, however, causes problems. With a microscope, we can use advanced filters to remove the incident laser wavelength. But sending light down an optical fibre generates unwanted signal, and we also need to remove elastically scattered light from the oesophagus. So we had to put a filter on the end of this tiny 2 mm fibre probe. In addition, we don’t want to collect photons that have travelled a long way through the body, so we needed a confocal system. We built a really complex probe, working in collaboration with John Day at the University of Bristol – it took a long time to optimize the optics and the engineering.

Are there options for diagnosing cancer in places that can’t be accessed via an endoscope?

Yes, we have also developed a smart needle probe that’s currently in trials. We are using this to detect lymphomas – the primary cancer in lymph nodes – in the head and neck, under the armpit and in the groin.

If somebody comes forward with lumps in these areas, they usually have a swollen lymph node, which shows that something is wrong. Most often it’s following an infection and the node hasn’t gone back down in size.

This situation usually requires surgical removal of the node to decide whether cancer is present or not. Instead, we can just insert our needle probe and send light in. By examining the scattered light and measuring its fingerprint we can identify if it’s lymphoma. Indeed, we can actually see what type of cancer it is and where it has come from. 

Currently, the prototype probe is quite bulky because we are trying to make it low in cost. It has to have a disposable tip, so we can use a new needle each time, and the filters and optics are all in the handpiece.

Are you working on any other projects at the moment?

As people don’t particularly want a needle stuck in them, we are now trying to understand where the photons travel if you just illuminate the body. Red and near-infrared light travel a long way through the body, so we can use near-infrared light to probe photons that have travelled many, many centimetres.

We are doing a study looking at calcifications in a very early breast cancer called ductal carcinoma in situ (DCIS) – it’s a Cancer Research UK Grand Challenge called DCIS PRECISION, and we are just moving on to the in vivo phase.

Calcifications aren’t necessarily a sign of breast cancer – they are mostly benign; but in patients with DCIS, the composition of the calcifications can show how their condition will progress. Mammographic screening is incredibly good at picking up breast cancer, but it’s also incredibly good at detecting calcifications that are not necessarily breast cancer yet. The problem is how to treat these patients, so our aim is to determine whether the calcifications are completely fine or if they require biopsy.

We are using Raman spectroscopy to understand the composition of these calcifications, which are different in patients who are likely to progress onto invasive disease. We can do this in biopsies under a microscope and are now trying to see whether it works using transillumination, where we send near-infrared light through the breast. We could use this to significantly reduce the number of biopsies, or monitor individuals with DCIS over many years.

Light can also be harnessed to treat disease, for example using photodynamic therapy as you mentioned earlier. Another approach is nanoparticle-based photothermal therapy, how does this work?

This is an area I’m really excited about. Nanoscale gold can enhance Raman signals by many orders of magnitude – it’s called surface-enhanced Raman spectroscopy. We can also “label” these nanoparticles by adding functional molecules to their surfaces. We’ve used unlabelled gold nanoparticles to enhance signals from the body and labelled gold to find things.

During that process, we also realized that we can use gold to provide heat. If you shine light on gold at its resonant frequency, it will heat the gold up and can cause cell death. You could easily blow holes in people with a big enough laser and lots of nanoparticles – but we want to do is more subtle. We’re decorating the tiny gold nanoparticles with a label that will tell us their temperature.

By measuring the ratio between Stokes and anti-Stokes scattering signals (which are enhanced by the gold nanoparticles), we can measure the temperature of the gold when it is in the tumour. Then, using light, we can keep the temperature at a suitable level for treatment to optimize the outcome for the patient.

Ideally, we want to use 100 nm gold particles, but that is not something you can simply excrete through the kidneys. So we’ve spent the last five years trying to create nanoconstructs made from 5 nm gold particles that replicate the properties of 100 nm gold, but can be excreted. We haven’t demonstrated this excretion yet, but that’s the process we’re looking at.

This research is part of a project to combine diagnosis and heat treatment into one nanoparticle system – if the Raman spectra indicate cancer, you could then apply light to the nanoparticle to heat and destroy the tumour cells. Can you tell us more about this?

We’ve just completed a five-year programme called Raman Nanotheranostics. The aim is to label our nanoparticles with appropriate antibodies that will help the nanoparticles target different cancer types. This could provide signals that tell us what is or is not present and help decide how to treat the patient.

We have demonstrated the ability to perform treatments in preclinical models, control the temperature and direct the nanoparticles. We haven’t yet achieved a multiplexed approach with all the labels and antibodies that we want. But this is a key step forward and something we’re going to pursue further.

We are also trying to put labels on the gold that will enable us to measure and monitor treatment outcomes. We can use molecules that change in response to pH, or the reactive oxygen species that are present, or other factors. If you want personalized medicine, you need ways to see how the patient reacts to the treatment, how their immune system responds. There’s a whole range of things that will enable us to go beyond just diagnosis and therapy, to actually monitor the treatment and potentially apply a boost if the gold is still there.

Looking to the future, what do you see as the most promising applications of light within healthcare?

Light has always been used for diagnosis: “you look yellow, you’ve got something wrong with your liver”; “you’ve got blue-tinged lips, you must have oxygen depletion”. But it’s getting more and more advanced. I think what’s most encouraging is our ability to measure molecular changes that potentially reveal future outcomes of patients, and individualization of the patient pathway.

But the real breakthrough is what’s on our wrists. We are all walking around with devices that shine light in us – to measure heartbeat, blood oxygenation and so on. There are already Raman spectrometers that sort of size. They’re not good enough for biological measurements yet, but it doesn’t take much of a technology step forward.

I could one day have a chip implanted in my wrist that could do all the things the gold nanoconstructs might do, and my watch could read it out. And this is just Raman – there are a whole host of approaches, such as photoacoustic imaging or optical coherence tomography. Combining different techniques together could provide greater understanding in a much less invasive way than many traditional medical methods. Light will always play a really important role in healthcare.

• This article is based on a session at the Institute of Physics’ Celebration of Physics in April 2025.

The post Harnessing the power of light for healthcare appeared first on Physics World.

As the world celebrates the 2025 International Year of Quantum Science and Technology, it’s natural that we should focus on the exciting applications of quantum physics in computing, communication and cryptography. But quantum physics is also set to have a huge impact on medicine and healthcare. Quantum sensors, in particular, can help us to study the human body and improve medical diagnosis – in fact, several systems are close to being commercialized.

Quantum computers, meanwhile, could one day help us to discover new drugs by providing representations of atomic structures with greater accuracy and by speeding up calculations to identify potential drug reactions. But what other technologies and projects are out there? How can we forge new applications of quantum physics in healthcare and how can we help discover new potential use cases for the technology?

Those are the some of the questions tackled in a recent report, on which this Physics World article is based, published by Innovate UK in October 2024. Entitled Quantum for Life, the report aims to kickstart new collaborations by raising awareness of what quantum physics can do for the healthcare sector. While the report says quite a bit about quantum computing and quantum networking, this article will focus on quantum sensors, which are closer to being deployed.

Sense about sensors

The importance of quantum science to healthcare isn’t new. In fact, when a group of academics and government representatives gathered at Chicheley Hall back in 2013 to hatch plans for the UK’s National Quantum Technologies Programme, healthcare was one of the main applications they identified. The resulting £1bn programme, which co-ordinated the UK’s quantum-research efforts, was recently renewed for another decade and – once again – healthcare is a key part of the remit.

As it happens, most major hospitals already use quantum sensors in the form of magnetic resonance imaging (MRI) machines. Pioneered in the 1970s, these devices manipulate the quantum spin states of hydrogen atoms using magnetic fields and radio waves. By measuring how long those states take to relax, MRI can image soft tissues, such as the brain, and is now a vital part of the modern medicine toolkit.

While an MRI machine measures the quantum properties of atoms, the sensor itself is classical, essentially consisting of electromagnetic coils that detect the magnetic flux produced when atomic spins change direction. More recently, though, we’ve seen a new generation of nanoscale quantum sensors that are sensitive enough to detect magnetic fields emitted by a target biological system. Others, meanwhile, consist of just a single atom and can monitor small changes in the environment.

There are lots of different quantum-based companies and institutions working in the healthcare sector

As the Quantum for Life report shows, there are lots of different quantum-based companies and institutions working in the healthcare sector. There are also many promising types of quantum sensors, which use photons, electrons or spin defects within a material, typically diamond. But ultimately what matters is what quantum sensors can achieve in a medical environment.

Quantum diagnosis

While compiling the report, it became clear that quantum-sensor technologies for healthcare come in five broad categories. The first is what the report labels “lab diagnostics”, in which trained staff use quantum sensors to observe what is going on inside the human body. By monitoring everything from our internal temperature to the composition of cells, the sensors can help to identify diseases such as cancer.

Currently, the only way to definitively diagnose cancer is to take a sample of cells – a biopsy – and examine them under a microscope in a laboratory. Biopsies are often done with visual light but that can damage a sample, making diagnosis tricky. Another option is to use infrared radiation. By monitoring the specific wavelengths the cells absorb, the compounds in a sample can be identified, allowing molecular changes linked with cancer to be tracked.

Unfortunately, it can be hard to differentiate these signals from background noise. What’s more, infrared cameras are much more expensive than those operating in the visible region. One possible solution is being explored by Digistain, a company that was spun out of Imperial College, London, in 2019. It is developing a product called EntangleCam that uses two entangled photons – one infrared and one visible (figure 1).

If the infrared photon is absorbed by, say, a breast cancer cell, that immediately affects the visible photon with which it is entangled. So by measuring the visible light, which can be done with a cheap, efficient detector, you can get information about the infrared photon – and hence the presence of a potential cancer cell (Phys. Rev. 108 032613). The technique could therefore allow cancer to be quickly diagnosed before a tumour has built up, although an oncologist would still be needed to identify the area for the technique to be applied.

Point of care

The second promising application of quantum sensors lies in “point-of-care” diagnostics. We all became familiar with the concept during the COVID-19 pandemic when lateral-flow tests proved to be a vital part of the worldwide response to the virus. The tests could be taken anywhere and were quick, simple, reliable and relatively cheap. Something that had originally been designed to be used in a lab was now available to most people at home.

Quantum technology could let us miniaturize such tests further and make them more accurate, such that they could be used at hospitals, doctor’s surgeries or even at home. At the moment, biological indicators of disease tend to be measured by tagging molecules with fluorescent markers and measuring where, when and how much light they emit. But because some molecules are naturally fluorescent, those measurements have to be processed to eliminate the background noise.

One emerging quantum-based alternative is to characterize biological samples by measuring their tiny magnetic fields. This can be done, for example, using diamond specially engineered with nitrogen-vacancy (NV) defects. Each is made by removing two carbon atoms from the lattice and implanting a nitrogen atom in one of the gaps, leaving a vacancy in the other. Behaving like an atom with discrete energy levels, each defect’s spin state is influenced by the local magnetic field and can be “read out” from the way it fluoresces.

One UK company working in this area is Element Six. It has joined forces with the US-based firm QDTI to make a single-crystal diamond-based device that can quickly identify biomarkers in blood plasma, cerebrospinal fluid and other samples extracted from the body. The device detects magnetic fields produced by specific proteins, which can help identify diseases in their early stages, including various cancers and neurodegenerative conditions like Alzheimer’s. Another firm using single-crystal diamond to detect cancer cells is Germany-based Quantum Total Analysis Systems (QTAS).

Matthew Markham, a physicist who is head of quantum technologies at Element Six, thinks that healthcare has been “a real turning point” for the company. “A few years ago, this work was mostly focused on academic problems,” he says. “But now we are seeing this technology being applied to real-world use cases and that it is transitioning into industry with devices being tested in the field.”

An alternative approach involves using tiny nanometre-sized diamond particles with NV centres, which have the advantage of being highly biocompatible. QT Sense of the Netherlands, for example, is using these nanodiamonds to build nano-MRI scanners that can measure the concentration of molecules that have an intrinsic magnetic field. This equipment has already been used by biomedical researchers to investigate single cells (figure 2).

Australian firm FeBI Technologies, meanwhile, is developing a device that uses nanodiamonds to measure the magnetic properties of ferritin – a protein that stores iron in the body. The company claims its technology is nine orders of magnitude more sensitive than traditional MRI and will allow patients to monitor the amount of iron in their blood using a device that is accurate and cheap.

Wearable healthcare

The third area in which quantum technologies are benefiting healthcare is what’s billed in the Quantum for Life report as “consumer medical monitoring and wearable healthcare”. In other words, we’re talking about devices that allow people to monitor their health in daily life on an ongoing basis. Such technologies are particularly useful for people who have a diagnosed medical condition, such as diabetes or high blood pressure.

NIQS Tech, for example, was spun off from the University of Leeds in 2022 and is developing a highly accurate, non-invasive sensor for measuring glucose levels. Traditional glucose-monitoring devices are painful and invasive because they basically involve sticking a needle in the body. While newer devices use light-based spectroscopic measurements, they tend to be less effective for patients with darker skin tones.

The sensor from NIQS Tech instead uses a doped silica platform, which enables quantum interference effects. When placed in contact with the skin and illuminated with laser light, the device fluoresces, with the lifetime of the fluorescence depending on the amount of glucose in the user’s blood, regardless of skin tone. NIQS has already demonstrated proof of concept with lab-based testing and now wants to shrink the technology to create a wearable device that monitors glucose levels continuously.

Body imaging

The fourth application of quantum tech lies in body scanning, which allows patients to be diagnosed without needing a biopsy. One company leading in this area is Cerca Magnetics, which was spun off from the University of Nottingham. In 2023 it won the inaugural qBIG prize for quantum innovation from the Institute of Physics, which publishes Physics World, for developing wearable optically pumped magnetometers for magnetoencephalography (MEG), which measure magnetic fields generated by neuronal firings in the brain. Its devices can be used to scan patients’ brains in a comfortable seated position and even while they are moving.

Quantum-based scanning techniques could also help diagnose breast cancer, which is usually done by exposing a patient’s breast tissue to low doses of X-rays. The trouble with such mammograms is that all breasts contain a mix of low-density fatty and other, higher-density tissue. The latter creates a “white blizzard” effect against the dark background, making it challenging to differentiate between healthy tissue and potential malignancies.

That’s a particular problem for the roughly 40% of women who have a higher concentration of higher-density tissue. One alternative is to use molecular breast imaging (MBI), which involves imaging the distribution of a radioactive tracer that has been intravenously injected into a patient. This tracer, however, exposes patients to a higher (albeit still safe) dose of radiation than with a mammogram, which means that patients have to be imaged for a long time to get enough signal.

A solution could lie with the UK-based firm Kromek, which is using cadmium zinc telluride (CZT) semiconductors that produce a measurable voltage pulse from just a single gamma-ray photon. As well as being very efficient over a broad range of X-ray and gamma-ray photon energies, CZTs can be integrated onto small chips operating at room temperature. Preliminary results with Kromek’s ultralow-dose and ultrafast detectors show they work with barely one-eighth of the amount of tracer as traditional MBI techniques.

“Our prototypes have shown promising results,” says Alexander Cherlin, who is principal physicist at Kromek. The company is now designing and building a full-size prototype of the camera as part of Innovate UK’s £2.5m “ultralow-dose” MBI project, which runs until the end of 2025. It involves Kromek working with hospitals in Newcastle along with researchers at University College London and the University of Newcastle.

Microscopy matters

The final application of quantum sensors to medicine lies in microscopy, which these days no longer just means visible light but everything from Raman and two-photon microscopy to fluorescence lifetime imaging and multiphoton microscopy. These techniques allow samples to be imaged at different scales and speeds, but they are all reaching various technological limits.

Quantum technologies can help us break the technological limits of microscopy

Quantum technologies can help us break those limits. Researchers at the University of Glasgow, for example, are among those to have used pairs of entangled photons to enhance microscopy through “ghost imaging”. One photon in each pair interacts with a sample, with the image built up by detecting the effect on its entangled counterpart. The technique avoids the noise created when imaging with low levels of light (Sci. Adv. 6 eaay2652).

Researchers at the University of Strathclyde, meanwhile, have used nanodiamonds to get around the problem that dyes added to biological samples eventually stop fluorescing. Known as photobleaching, the effect prevents samples from being studied after a certain time (Roy. Soc. Op. Sci. 6 190589). In the work, samples could be continually imaged and viewed using two-photon excitation microscopy with a 10-fold increase in resolution.

Looking to the future

But despite the great potential of quantum sensors in medicine, there are still big challenges before the technology can be deployed in real, clinical settings. Scalability – making devices reliably, cheaply and in sufficient numbers – is a particular problem. Fortunately, things are moving fast. Even since the Quantum for Life report came out late in 2024, we’ve seen new companies being founded to address these problems.

One such firm is Bristol-based RobQuant, which is developing solid-state semiconductor quantum sensors for non-invasive magnetic scanning of the brain. Such sensors, which can be built with the standard processing techniques used in consumer electronics, allow for scans on different parts of the body. RobQuant claims its sensors are robust and operate at ambient temperatures without requiring any heating or cooling.

Agnethe Seim Olsen, the company’s co-founder and chief technologist, believes that making quantum sensors robust and scalable is vital if they are to be widely adopted in healthcare. She thinks the UK is leading the way in the commercialization of such sensors and will benefit from the latest phase of the country’s quantum hubs. Bringing academia and businesses together, they include the £24m Q-BIOMED biomedical-sensing hub led by University College London and the £27.5m QuSIT hub in imaging and timing led by the University of Birmingham.

Q-BIOMED is, for example, planning to use both single-crystal diamond and nanodiamonds to develop and commercialize sensors that can diagnose and treat diseases such as cancer and Alzheimer’s at much earlier stages of their development. “These healthcare ambitions are not restricted to academia, with many startups around the globe developing diamond-based quantum technology,” says Markham at Element Six.

As with the previous phases of the hubs, allowing for further research encourages start-ups – researchers from the forerunner of the QuSIT hub, for example, set up Cerca Magnetics. The growing maturity of some of these quantum sensors will undoubtedly attract existing medical-technology companies. The next five years will be a busy and exciting time for the burgeoning use of quantum sensors in healthcare.

The post How quantum sensors could improve human health and wellbeing appeared first on Physics World.

In this episode of the Physics World Weekly podcast we explore the career opportunities open to physicists and engineers looking to work within healthcare – as medical physicists or clinical engineers.

Physics World’s Tami Freeman is in conversation with two early-career physicists working in the UK’s National Health Service (NHS). They are Rachel Allcock, a trainee clinical scientist at University Hospitals Coventry and Warwickshire NHS Trust, and George Bruce, a clinical scientist at NHS Greater Glasgow and Clyde. We also hear from Chris Watt, head of communications and public affairs at IPEM, about the new IPEM careers guide.

• This episode was created in collaboration with IPEM, the Institute of Physics and Engineering in Medicine. IPEM owns the journal Physics in Medicine & Biology.

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