Fiber medicine

Fiber-printed sensor for label-free detection of bacteria

Innovation

Fiber-printed sensor for label-free detection of bacteria

Research, fiber optics and 3D printing in new techniques to fight old enemies

Posted: Wednesday, March 23, 2022 – 12:01 PM

AAccording to the World Health Organization (WHO), antibiotic resistance is one of the biggest threats to health, food security and development in the world today. This bacterial immunity is a natural evolutionary process, which is further accelerated by the misuse of antibiotic treatments. For more precise treatment of infections, in situ characterization of the infected region would be ideal as it would allow specific treatment against pathogens.

With this in mind, researchers from imperial college london has developed a new fiber-optic Raman spectroscopy sensor for label-free identification of bacteria using Nanoscribe’s microfabrication technology.

Gold coated fiber optic SERS probe: The green color of the probe is a diffraction phenomenon from the microstructured surface. Image: JA Kim, Imperial College London

The invention of antibiotics is certainly one of the great milestones of modern medicine and has allayed many people’s fears of infectious diseases such as tuberculosis or pneumonia. However, medical and biological experts are again focusing on fighting bacterial infections. Due to the high use or even misuse of antibiotics, bacteria are becoming increasingly resistant to their treatment, and even minor infections can once again become deadly. To counteract this, antibiotics should only be administered when necessary and in accordance with the respective disease pattern.


Schematic illustration of the fiber-based SERS probe. Laser light is coupled into the optical fiber and excites signal hotspots on the nanostructured surface of the fiber probe. In interaction with the analyte, the enhanced Raman signal (SERS signal) is generated and collected by the optical fiber. Image: JA Kim, Imperial College London

In situ characterization of bacteria by fiber optic SERS probe

Imperial College London scientists are addressing this global challenge by developing a fiber optic sensor for label-free detection and characterization of bacteria. This miniaturized sensor, based on surface-enhanced Raman spectroscopy (SERS), is the first of its kind and can potentially be integrated into medical endoscopes for in situ analysis of inflamed tissue.


Study to optimize the design of a single voxel array. The voxel spacing is changed and the effect on the SERS signal is analyzed. Incredibly small spacing distances of 400 nm could be resolved in this study. However, the maximum SERS signal was found at 700 nm spacing. Image: JA Kim, Imperial College London

Raman spectroscopy is a powerful analytical technique for organic and biological samples, allowing the characterization of samples such as bacteria based on their individual spectral fingerprint. The inherently weak nature of Raman scattering can be enhanced by metallized micro- and nanostructured surfaces, creating signal hotspots that interact with the sample.

In their study, the scientists 3D printed these micro and nanostructures on facets of the optical fibers using two-photon polymerization (2PP), then coated them with a thin layer of gold. For SERS measurements, laser light is coupled into the optical fiber and excites signal hotspots on the nanostructured surface of the fiber probe. In interaction with the analyte, the SERS signal is generated and collected by the optical fiber.


Microstructures printed directly on an optical fiber for an optical sensor that uses the principle of surface-enhanced Raman spectroscopy to detect bacteria. Image: JA Kim, Imperial College London

Rapid prototyping with short design iteration cycles

In a first design study, scientists analyzed the SERS effect of various micro- and nano-patterns printed on a plane glass substrate using Nanoscribe’s 2PP technology. A hexagonally arranged single-voxel array was found to be the most efficient sample. With rapid design iterations, researchers further optimized the spacing between individual array voxels and fabricated samples with incredibly small spacing distances of just 400 nanometers, which is challenging but actually still feasible with microfabrication. based on 2PP.

A second design that proved effective for SERS measurements was a microspike array that guides and focuses signal hotspots at the peaks. Specifically printed on fibers, this design showed increased mechanical stability compared to the single-voxel array and was further investigated for the detection of E. coli bacteria.

For the final fiber optic SERS probe, the researchers printed the optimized microstructures directly onto the facets of the fiber and demonstrated its analytical capabilities by detecting unlabeled E. coli bacteria.

Nanoscribe’s solution for inclined, compensated and aligned fiber printing

For the fiber-printed SERS probe, the researchers had to overcome several manufacturing challenges. First, they designed a custom fiber holder that allows printing on the facet of a fiber. Next, the printed object must be perfectly aligned with the fiber optic core to excite the microfabricated Raman hotspots. A remaining challenge, especially for watermark structures such as the single-voxel array, is compensating for a potentially tilted substrate surface. The inclined surface of the optical fiber substrate resulted in low yield of SERS active microstructures.

To drive innovations in photonics and applications in medical instrumentation and optical sensing, such as the intriguing fiber optic SERS probe, Nanoscribe recently introduced its latest 3D printer, Quantum Alignment X. With its exclusive fiber-printing assembly and tilt correction in all spatial directions, the new 3D printer can already provide the answer to the challenges of fiber-printed SERS probes and pave the way for further improvements and new innovations.

Read the scientific publication here: “Fiber-optic SERS probes fabricated using two-photon polymerization for rapid detection of bacteria.”

First published on February 24, 2022 on Nanoscribe News.