A noninvasive strategy for multi-disease diagnosis via multi-sensor platform: integrative analysis of five years of exhaled breath–based diagnostics for seven diseases

Alessandro Zompanti¹Giorgio Pennazza^1*Simone Grasso¹Anna Sabatini¹Maria Vittoria Di Loreto¹Costanza Cenerini¹Ludovica La Monica¹Luca Vollero¹Raffaele Antonelli Incalzi²Claudio Pedone²Panaiotis Finamore²Simone Scarlata²Antonio De Vincentis²Antonio Picardi²Pierfilippo Crucitti²Filippo Longo²Gaetano Rocco³Andrea Segreti²Francesco Grigioni²Marco Santonico¹

• ¹Campus Bio-Medico University, Rome, Italy
• ²Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
• ³Memorial Sloan Kettering Cancer Center, New York, United States

Sensors used for collecting high-value physiological and biochemical data strongly support a precision medicine approach, by enabling the integration of these complex datasets with routine clinical outcomes to provide more accurate diagnostic and prognostic evaluations. Building on extensive experience in this field, the authors have developed multi-sensor technologies designed to analyze multiple biological fluids, with a particular focus on exhaled breath both in as it is and processed in liquid media. These technologies have been implemented in a large-scale clinical study involving 863 patients affected by seven different diseases, allowing for the acquisition of heterogeneous data suitable for computational modeling and the identification of disease-related characteristics. By integrating multiple sensors and analyzing diverse breath samples, this work aims to generate a comprehensive reference library of breathprints and thereby advance the clinical applicability of breath analysis. The study demonstrates the potential of this multi-omic, multisensory approach to differentiate healthy individuals from patients with various respiratory, cardiovascular, and metabolic disorders, while pioneering investigations of exhaled breath in liquid media—although conducted on a smaller patient cohort—highlight promising opportunities for technological innovation in multisensory diagnostics. While the overall results support the feasibility and potential impact of this methodology, further research will be required to refine the technique, enlarge patient cohorts, and improve the accuracy and specificity of disease detection.