Detection of Anti-Mycobacterium leprae Antibodies in Leprosy Contacts Using a Label-Free Approach with the Heat-Transfer Method.

Early detection of Mycobacterium leprae infection is essential to interrupt leprosy transmission and guide prophylactic interventions. Current diagnostic strategies rely largely on clinical signs, and laboratory tools lack sensitivity to detect asymptomatic individuals, who can play a critical role in disease transmission and evolve to disease as well. In this study, we report the development of a heat-transfer method (HTM)-based biosensor employing a newly designed multiepitope protein receptor, capable of detecting anti-M. leprae antibodies in human serum, with sensitivity for leprosy contacts. The protein, initially tested in ELISA assays, was then immobilized on aluminum chips, and its successful attachment and functionality were confirmed using FTIR, EDX, ELISA-like, and confocal fluorescence assays. Evaluation of the sensor was performed using an HTM transducing platform, where thermal measurements revealed a clear response to antibody binding that is serum dilution-dependent as it is in established methods such as ELISA. The biosensor distinguished serum from M. leprae-exposed individuals from that of non-exposed controls and a tuberculosis sample, with effect sizes up to four times higher. Notably, responses were comparable to the ones obtained using ELISA at similar serum dilution. These findings demonstrate, for the first time, the feasibility of using a thermal biosensing platform to detect specific antibodies in a clinically relevant scenario, paving the way for a sensitive, low-cost, and point-of-care tool for early leprosy detection and contact surveillance. This strategy addresses the critical challenge of identifying M. leprae exposure and holds potential for broader application in infectious disease diagnostics.