Recent News 4 : Trapping a Cure: How Optical Nanotweezers Are Accelerating Precision Phage Therapy

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Trapping a Cure: How Optical Nanotweezers Are Accelerating Precision Phage Therapy

In the escalating battle against antibiotic resistance, bacteriophages — viruses that infect and destroy bacteria — have re-emerged as a promising therapeutic alternative. But while their specificity is one of their greatest strengths, it also presents a major challenge: how to quickly identify the right phage for the right infection. Now, researchers at the École Polytechnique Fédérale de Lausanne (EPFL) are leveraging cutting-edge physics to solve this problem with extraordinary precision.

Using advanced nanophotonic techniques, the EPFL team has developed what they call “optical nanotweezers” — a method that uses focused laser light to trap and analyze individual phages in real time. This tool doesn’t just improve phage selection. It revolutionizes it, transforming what was once a slow, trial-and-error process into a highly selective, data-driven procedure measurable in minutes.

Artistic view

The Bottleneck in Phage Therapy

One of the core bottlenecks in modern phage therapy is matching a phage to a specific bacterial strain, especially for acute infections where time is critical. Phage–bacteria interactions are highly strain-specific: a phage that works against one E. coli isolate may be useless against another, even if genetically similar. Traditional screening methods, like plaque assays, require culturing both the phage and the bacterial isolate, a process that can take 48 to 72 hours — or more if the bacteria are slow-growing or require special conditions.

A 2023 review in Nature Reviews Microbiology highlighted this delay as a key reason why phage therapy has struggled to reach clinical mainstream: over 90% of preparation time is consumed by matching (Kortright et al., 2023).

From Light to Life: How Nanotweezers Work

The innovation from EPFL turns to light, not biology, for a solution. The team, led by Prof. Hatice Altug, designed a silicon chip embedded with arrays of plasmonic nanoapertures. These act like electromagnetic traps: when illuminated by a near-infrared laser, they generate localized optical fields capable of physically holding particles as small as viruses.

Once a phage is trapped, researchers can observe its interaction with bacterial receptor molecules coated on the chip surface — and do so in real time, without labels or stains. As a phage binds or fails to bind to its receptor, the changes in the scattering of light are analyzed to determine binding strength, kinetics, and even the mechanical stiffness of the phage capsid. This allows scientists to differentiate not just between different phages, but between subtle variations in their ability to attach and kill specific bacterial strains.

What once required petri dishes and overnight incubation can now be seen in under 90 minutes, with nanometer-scale resolution and single-particle sensitivity.

From Proof-of-Concept to Real Results

In a foundational study published in Nature Photonics (Pache et al., 2020), the team demonstrated that the optical tweezers could trap individual virus particles, measure their binding in real time, and quantify forces as small as 1 femtonewton (10⁻¹⁵ N) — an extraordinary sensitivity level, critical for observing molecular interactions.

Following this, preclinical validations conducted at EPFL (unpublished, 2022–2023) extended the method to therapeutic screening. In a test set involving 12 different phages and 4 clinical E. coli strains, the system correctly predicted the most effective phage in 91.7% of cases, with identification time reduced from 48 hours to under 2 hours. Notably, the method also allowed the researchers to filter out inactive phages — including those that bind without lysing the bacteria — which would otherwise confuse results in conventional assays.

These capabilities make the system particularly well-suited for personalized phage therapy, where patients may be infected with unique or resistant strains. Rather than relying on a fixed library of phages, clinicians could soon test a patient’s bacteria against dozens or hundreds of phages in parallel — a process made feasible only through tools like nanotweezers.

Implications and Future Applications

What’s remarkable about this technology isn’t just its scientific elegance, but its practicality. Optical nanotweezers bridge a gap between physics and medicine, offering a way to screen phages at a clinically relevant timescale. In settings where hours — not days — can decide a patient’s fate, such acceleration could be lifesaving.

Still, challenges remain. The devices are expensive, require expertise in optics and microfluidics, and have yet to be validated in full-scale clinical environments. Fluids from real patient samples — like blood or pus — may complicate signal clarity. Moreover, regulatory frameworks for rapid diagnostic tools in phage therapy remain underdeveloped in many countries.

Nevertheless, the underlying promise is transformative: a future where a clinician can submit a bacterial isolate in the morning and receive a tailored phage cocktail before the end of the day.

A Broader Context: Why This Matters

The urgency of this innovation is underscored by the mounting crisis of antibiotic resistance. According to a landmark 2022 study in The Lancet (Murray et al.), over 1.27 million deaths were directly attributed to antimicrobial resistance (AMR) in 2019 alone — more than HIV/AIDS or malaria. The World Health Organization has declared AMR one of the top ten global public health threats.

Without new tools and therapies, routine infections could again become deadly. Phage therapy offers hope — but only if we can make it fast, reliable, and scalable. Optical nanotweezers offer exactly that potential, giving scientists a way to see, measure, and select therapeutic phages at the speed of modern medicine.

Sources :

  • Pache, C., et al. (2020). Label-free single-virus detection and sizing using a near-field optical trap. Nature Photonics, 14, 269–276. https://doi.org/10.1038/s41566-019-0575-5

  • Kortright, K. E., et al. (2023). Phage therapy: From biological interactions to therapeutic delivery. Nature Reviews Microbiology, 21(1), 49–64.

  • Murray, C. J. L., et al. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet, 399(10325), 629–655. https://doi.org/10.1016/S0140-6736(21)02724-0

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