Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.In biochemical sensing field, Lab-on -Fiber (LOF) based devices essentially consist on the combination of optical resonant nanostructures (typically patterned metallic slab supporting surface plasmon resonances (SPR)) and functional coating materials integrated on the optical fiber tip [1][2][3][4][5][6][7] . LOF technology is continuously leading to the development of novel biosensing probes with unique properties in term of size, weight and ease of interrogation 4,5 . In addition to point of care applications, LOF based devices seem to be particularly promising for in-vivo analysis systems, thanks to the intrinsic properties of optical fibers that make them easily integrable inside medical catheters or needles 8 . Typically, the working principle of LOF probes relies on the affinity interaction of a ligand attached to the sensor surface with the target molecule present in a liquid solution at a certain concentration. However, standard label-free approaches fail when target molecules are small, for example about a few hundreds of dalton. In that case, the ligand/analyte binding process produces a biological layer that is not thick enough for providing a local refractive index (RI) change that is optically detectable by the sensor. Analogous issues occur in such applications where the detection of larger analytes with very low limit of detection (LOD) is required. To enhance the sensitivity, gold and magnetic nanoparticles have been proposed as "molecular concentrators" able to localize multiple binding events on a single particle, and successively deliver target analyte from the solution to the sensor surface [9][10][11] . At the same time, approaches exploiting hydrogels (HGs) have been proposed 12,13 . HGs basically allow to: i) increase the analyte loading capacity by translating a conventional 2D interaction surface into a 3D volume inter...