The present proposal deals with the development of a novel optical platform for biosensing, which makes use of the random laser as optically active sensing tool combined with a highly sensitive avalanche photodetector based receiver. In a random laser the optical feedback is assured by diffusion rather than by the coupling with an optical cavity as in a conventional laser. For this reason its emission properties are extremely sensitive to small scale alterations in dimension, distribution and optical response of scatterers, providing a great opportunity to create a new kind of active optical sensors. As for the random laser, two different configurations will be considered, characterized by two different active elements. In one case the active element is constituted by a fluorophore solution properly excited and contained in a small hollow core glass bulge located at the end of an optical fiber. In the second case, the active element is represented by a rare-earth-doped optical fiber with a distal end dipped in the liquid sample. In both cases the photoreceiver continuously tracks both intensity and wavelength variations of the random laser. These two different configurations will be coupled to two different assay formats. Homogeneous bioassay with the interaction of the analyte with the biologic recognition element (BRE) in solution and heterogeneous bioassay with the analyte interacting with the BRE within a sensing layer will be the two different "bioconfiguration" coupled with two different random laser configurations and capable to tune the random laser emission. In this way changes in the lasing properties of random laser can be associated to the concentration of the analyte, which will be detected reaching very low limit of detection. In particular the new optical platform will be applied to the detection of Tau protein, the detection of which is becoming strategic in pathologies and dementias of the nervous system such as Alzheimer's and Parkinson's disease.
The objective of this proposal is extremely ambitious with the purpose of developing a novel optical platform for biosensing based on the use of random laser. It's noteworthy to observe that there is no example described in the literature concerning the use of random laser for biosensing purposes. This platform should be characterized by a better sensitivity with respect to the optofluidic biolasers where the active medium contains the analyte and this should consent to achieve ultralow limit of detection.
This should be true for both the optical configurations, whose important and common aspect is represented by the fact that in both cases the sample is analysed at the distal end of an optical fiber with all the typical advantages associated to the use of optical fibers: easy handling, miniaturization of the sensing probe, the possibility of reaching locations difficult to be accessed. In biomedical field, which is the area of application of the present proposal, this can pave the way to the in-vivo use on patients with also the possibility of invasive applications and this can really constitute a noticeable step-forward in the development of biomedical devices.
The development of a novel platform for biosensing based on random laser will have a deep impact, leading to the detection of biochemical with an ultra-low limit of detection. The present proposal deals with the use of the platform to perform high sensitive bioassays. In this operational framework, the present platform, considering the potential integration in a compact device, can have a strong impact in the biomedical field in the area of point of care testing (POCT) devices, devices able to carry out rapid and reliable measurements of chemical and biochemical parameters near the patient's bed. They should allow the rapid formulation of a reliable diagnosis and / or the quick choice of the most appropriate therapy, avoiding the use of centralized laboratory analyses which implies to wait for the results a period ranging from a few hours up to, sometimes, a whole day. They are becoming essential to the analysis of all those pathologies, where a rapid medical intervention is crucial to patient life [19].
Besides the application to bioassay, this novel platform can find applications whenever a portable system is required to make analysis on field and this extends its impact also to other areas of applications, such as in industrial process for the on-line product control of biochemicals or whenever an in-situ analysis of biochemical is required.
As far as the two different configurations is concerned, even if only one of them will be pushed up to the integration in a final device, they both can provide a high degree of novelty; the different configurations of the sensing probe, in one case the container containing the fluorophore at the end of the optical fiber (Figure 1) and in the second case just the optical fiber dipped in the sample volume provide a degree freedom to the optical platform with the possibility of applying it to a large variety of samples, either in gaseous or liquid or solid state.
The fact that the measuring area/volume is interrogated with an optical fiber constitutes an important added value since this feature leads to the possibility of taking the advantages typical of the use of the optical fibers: immunity from electromagnetic interference, easy handling, safe access in explosive areas, etc.
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