Symptomatology is a powerful approach to diseases diagnosis, however, often the disease is far advanced when symptoms manifest or become evident. At this point, valuable time has been lost, making it more difficult to overcome the disease for the patient. For that reason, the development of novel tools capable of early screening for diseases is becoming the new paradigm in clinical testing and diagnostics. In the previous section, we addressed the analytical capabilities of MOFbased SERS substrates for VOCs from both gas-and liquid-phase. Interestingly, many of these analytes are not exclusively of interest in the context of environmental and industrial monitoring, but are relevant also to other application fields. For example, aldehydes and ketones are produced by our bodies through metabolic processes and serve as indicators of our health status. In fact, there are several VOCs with proved correlations to medical conditions, some of which are presented in Figure . This is particularly true for cancer diagnosis, especially for lung cancer (LC), which has one of the larger incidence and mortality worldwide. There are different LC diagnostic biomarkers and tools, ranging from imaging analysis to the liquid biopsy based on the analysis of autoantibodies and microRNA, 124 as summarized in Figure . Besides these, detection pf VOCs in exhaled breath represents an important method suitable for noninvasive diagnostics of LC and other diseases and it has been subject of intensive research activity over the last few years. Even though biomarkers associated with LC can be found in bodily fluids including blood, VOCs are generated either by or in the microenvironment surrounding the cancerous cells and therefore are in part excreted by the lungs via the exhaled breath. 128 Different bioanalytical tools have been proposed for the detection of VOCs for diagnostic purposes 129 and among them SERS is in the spotlight due to its fingerprinting capabilities. It is expected then that the combination of SERS with MOFs for capturing and concentrating the VOCs exhaled in breath can push forward the field. and coated them with ZIF-8 in order to yield the composite GSPs@ZIF-8. In this core-shell structure, GSPs generate plasmonic hotspots and the MOF contributes to their further spatial confinement as well as to slowing the gas flow on the GSP surface. When employed as SERS substrate, the detection of aldehydes, one of the most well-established biomarkers for LC, was carried out. As schematized in Figure , MOF-based SERS substrate was then employed for the detection of several aldehydes including 4-ethylbenzaldehyde, which is a classic LC biomarker. GSP were modified in this experiment by 4-aminothiophenol, providing them with amino groups suitable for reaction with aldehydes through the so-called Schiff reaction. The signal from the generated C=N bond upon Schiff reaction was normalized against the intensity of the Raman peak at 1078 cm -1 associated with C-S from the anchored thiol, serving then as internal standard (see Figure ).