This paper presents the development of an extremely sensitive and selective acetone sensor prototype which can be used as a platform for non-invasive diabetes detection through exhaled human breath. The miniaturized sensors were produced in high yield with the use of standard microfabrication processes. The sensors were based on a heterostructure composed of MoO3 and nano-porous silicon (NPS). Features like acetone selective, enhanced sensor response and 0.5 ppm detection limit were observed upon introduction of MoO3 on the NPS. The sensors were found to be repeatable and stable for almost 1 year, as tested under humid conditions at room temperature. It was inferred that the interface resistance of MoO3 and NPS played a key role in the sensing mechanism. With the use of breath analysis and lab-on-chip, medical diagnosis procedures can be simplified and provide solutions for point-of-care testing. © 2018 IOP Publishing Ltd.