Nanotweezers Use Light to Manipulate and Identify Bacteriophages Without Using Bioreceptors, Revolutionizing Phage-Based Therapies

Antibiotic misuse and the lack of drugs that act through novel mechanisms negatively affect the management of difficult-to-treat infections. This challenge poses a major threat to human health.

Because of this, scientists are on a constant quest for alternative ways to treat bacterial infections. A promising potential intervention to address this concern is the therapeutic use of bacteriophages or phages.

Potential of Phage Therapy

Bacteriophages refer to viruses that solely and selectively target and kill bacteria. They can infect specific species of bacteria without negatively affecting human or animal cells. Phages exist in thousands of different types. They can also be found anywhere, from the soil to the human guts.

The ability of phages to kill bacteria is harnessed to create a potential treatment known as phage therapy. It was developed as a treatment for bacterial infections a decade before the discovery of penicillin.

Antibiotics obliterate harmful bacteria while damaging the microbiota at the same time. In contrast, each phage has evolved to target specific bacterial strains narrowly. While phage therapy gains attraction as a viable alternative to traditional antibiotics, finding the right bacteriophage for a given infection remains challenging. Conventional methods involve inconvenient culture and time-consuming assays.

Manipulating Bacteriophages With Nanotweezers

At Ecole Polytechnique Federale de Lausanne, experts have developed an on-chip nanotweezers that can trap and manipulate bacteria and virions using only minimal light energy. They collaborated with the CEA Grenoble and the Lausanne University Hospital (CHUV) to conduct the study entitled "Optical Trapping and Fast Discrimination of Label-Free Bacteriophages at the Single Virion Level."

Nanotweezers are optical tweezers, scientific instruments that use a highly focused laser beam to hold and manipulate microscopic and sub-microscopic objects such as atoms in three dimensions. Light creates a gradient force that attracts particles towards a high-intensity focal point, keeping them in place without physical contact.

Optical tweezers were first invented by physicist Arthur Ashkin in 1986 while working out the principles behind them in the late 1960s. This innovation won Ashkin the 2018 Nobel Prize in Physics, and since then, optical tweezers have remained an intense field of research.

Optical tweezers come in various types. For instance, free-space optical tweezers can manipulate an object in an open environment like air or liquid without physical barriers or structures guiding the light. But in this study, Nicolas Villa and Enrico Tartari led a team of researchers in creating nanotweezers embedded in an optofluidic device. This device integrates optical and fluidic technologies on a single chip.

The chip contains nanotweezers, the silicon-based photonic crystal cavities, which are small traps that gently nudge the phages into position using a light-generated force field. This enables scientists to control individual bacteria and virions precisely and obtain real-time information about the trapped microorganisms.

This technology is unique because it can distinguish between various types of phages without surface receptors, which are time-consuming and sometimes ineffective. Instead, the novel nanotweezers distinguish between phages by reading the unique changes each particle brings to the properties of light. The label-free approach can potentially accelerate the selection of therapeutic phages, providing a faster turnaround for phage-based treatments.

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