Alternative fuel sources, such as hydrogen-enriched natural gas (HENG), are highly sought after by governments globally for lowering carbon emissions. Consequently, the recognition of hydrogen as a valuable zero-emission energy carrier has increased, resulting in many countries attempting to enrich natural gas with hydrogen; however, there are rising concerns over the safe use, storage, and transport of H2 due to its characteristics such as flammability, combustion, and explosivity at low concentrations (4 vol%), requiring highly sensitive and selective sensors for safety monitoring. Microfluidic-based metal–oxide–semiconducting (MOS) gas sensors are strong tools for detecting lower levels of natural gas elements; however, their working mechanism results in a lack of real-time analysis techniques to identify the exact concentration of the present gases. Current advanced machine learning models, such as deep learning, require large datasets for training. Moreover, such models perform poorly in data distribution shifts such as instrumental variation. To address this problem, we proposed a Sparse Autoencoder-based Transfer Learning (SAE-TL) framework for estimating the hydrogen gas concentration in HENG mixtures using limited datasets from a 3D printed microfluidic detector coupled with two commercial MOS sensors. Our framework detects concentrations of simulated HENG based on time-series data collected from a cost-effective microfluidic-based detector. This modular gas detector houses metal–oxide–semiconducting (MOS) gas sensors in a microchannel with coated walls, which provides selectivity based on the diffusion pace of different gases. We achieve a dominant performance with the SAE-TL framework compared to typical ML models (94% R-squared). The framework is implementable in real-world applications for fast adaptation of the predictive models to new types of MOS sensor responses.