The search for extraterrestrial extant or extinct life in our Solar System will require highly capable instrumentation and methods for detecting low concentrations of biosignatures. This paper introduces the Supercritical CO 2 and Subcritical H 2 O Analysis (SCHAN) instrument, a portable and automated system that integrates supercritical fluid extraction (SFE), supercritical fluid chromatography (SFC), and subcritical water extraction coupled with liquid chromatography. The instrument is compact and weighs 6.3 kg, making it suitable for spaceflight missions to planetary bodies. Traditional techniques, such as gas chromatography−mass spectrometry (MS), face challenges with involatile and thermally labile analytes, necessitating derivatization. The SCHAN instrument, however, eliminates the need for derivatization and cosolvents by utilizing neat supercritical CO 2 with water as an additive. This SFE-SFC-MS method gives efficient lipid biosignature separations with median detection limits of 10 pg/g (ppt) for fatty acids and 50 pg/g (ppt) for sterols. Several free fatty acids and cholesterol were among the detected peaks in biologically lean samples from the Atacama Desert, demonstrating the instrument's potential for in situ life detection missions. The SCHAN instrument addresses the challenges of conventional systems, offering a compact, portable, and spaceflight-compatible tool for the analysis of organics for future astrobiology-focused missions.