Integration of plasmonic nanostructures with fiber‐optics‐based neural probes enables label‐free detection of molecular fingerprints via surface‐enhanced Raman spectroscopy (SERS), and it represents a fascinating technological horizon to investigate brain function. However, developing neuroplasmonic probes that can interface with deep brain regions with minimal invasiveness while providing the sensitivity to detect biomolecular signatures in a physiological environment is challenging, in particular because the same waveguide must be employed for both delivering excitation light and collecting the resulting scattered photons. Here, a SERS‐active neural probe based on a tapered optical fiber (TF) decorated with gold nanoislands (NIs) that can detect neurotransmitters down to the micromolar range is presented. To do this, a novel, nonplanar repeated dewetting technique to fabricate gold NIs with sub‐10 nm gaps, uniformly distributed on the wide (square millimeter scale in surface area), highly curved surface of TF is developed. It is experimentally and numerically shown that the amplified broadband near‐field enhancement of the high‐density NIs layer allows for achieving a limit of detection in aqueous solution of 10⁻⁷ m for rhodamine 6G and 10⁻⁵ m for serotonin and dopamine through SERS at near‐infrared wavelengths. The NIs‐TF technology is envisioned as a first step toward the unexplored frontier of in vivo label‐free plasmonic neural interfaces.

Integration of plasmonic structures on step‐index optical fibers is attracting interest for both applications and fundamental studies. However, the possibility to dynamically control the coupling between the guided light fields and the plasmonic resonances is hindered by the turbidity of light propagation in multimode fibers (MMFs). This pivotal point strongly limits the range of studies that can benefit from nanostructured fiber optics. Fortunately, harnessing the interaction between plasmonic modes on the fiber tip and the full set of guided modes can bring this technology to a next generation progress. Here, the intrinsic wealth of information of guided modes is exploited to spatiotemporally control the plasmonic resonances of the coupled system. This concept is shown by employing dynamic phase modulation to structure both the response of plasmonic MMFs on the plasmonic facet and their response in the corresponding Fourier plane, achieving spatial selective field enhancement and direct control of the probe's work point in the dispersion diagram. Such a conceptual leap would transform the biomedical applications of holographic endoscopic imaging by integrating new sensing and manipulation capabilities.

Adaptive optics methods have long been used to perform complex light shaping at the output of a multimode fiber (MMF), with the specific aim of controlling the emitted beam in the near field and enabling the realization of a new generation of endoscopes based on a wide variety of spectroscopic techniques. Gaining control of other emission properties, including the far-field pattern and the phase of the generated beam, would open up the possibility for multimode fibers to act as miniaturized multi-beam steering components and to implement phase-encoded imaging and sensing. In this study, we employ phase modulation using a spatial light modulator at the input of a multimode fiber to generate multiple, low divergence rays with controlled angles and phase at the fiber output. Direct measurement of the output angle and the divergence and phase of the generated beams show how wavefront engineering can be employed to perform complex far-field structuring of the emission of a MMF.

Pre-shaping light to achieve desired amplitude distributions at the tip of a multimode fiber (MMF) has emerged as a powerful method allowing a wide range of imaging techniques to be implemented at the distal facet. Such techniques rely on measuring the transmission matrix of the optically turbid waveguide which scrambles the coherent input light into an effectively random speckle pattern. Typically, this is done by measuring the interferogram between the output speckle and a reference beam. In recent years, an optical setup where the reference beam passes through the MMF has become an attractive configuration because of the high interferometric stability of the common optical path. However, the merits and drawbacks of an internal reference beam remain controversial. The measurement of the transmission matrix is known to depend on the choice of internal reference and has been reported to result in “blind spots” due to phase singularities of the reference beam. Here, we describe how the focussing efficiency of the calibration can be increased by several percent by optimising the choice of internal reference beam.

Within the realm of optical neural interfaces, the exploration of plasmonic resonances to interact with neural cells has captured increasing attention among the neuroscience community. The interplay of light with conduction electrons in nanometer-sized metallic nanostructures can induce plasmonic resonances, showcasing a versatile capability to both sense and trigger cellular events. We describe the perspective of generating propagating or localized surface plasmon polaritons on the tip of an optical neural implant, widening the possibility for neuroscience labs to explore the potential of plasmonic neural interfaces.

We propose a low-invasive method to enable implantable, large volume Raman spectroscopy in arbitrarily deep brain regions of the mouse brain. Using a single tapered fiber as thin as 1 μm at the tip, we identified diagnostic markers of brain metastasis - the most frequent brain tumor in human adults - with overall accuracy ≥ 90%. We view our approach as a promising complement to the existing palette of tools for optical interrogation of the brain.