High-throughput chip-calorimeter using a Bi₂Te₃ thermopile heat flux sensor array

Modern thermoelectric modules have emerged as promising platforms for precision thermal analysis in biological and chemical applications. This study presents a high-throughput microcalorimeter employing a patterned bismuth telluride (Bi₂Te₃) thermopile array as integrated heat flux sensors, overcoming the throughput limitations of conventional calorimetric systems. Through finite element analysis-guided device optimization, we established that increasing thermocouple height from 0.4 mm to 0.8 mm reduces thermal conductance, achieving around 1 $V·W^{-1}$ power sensitivity. The system demonstrated dual-mode calibration methods using both the electrical (Joule heating) and the chemical (water-ethanol mixing enthalpy) references. Device functionality was validated through real-time monitoring of Escherichia coli metabolism, revealing distinct thermal signatures upon antibiotic challenge. The antimicrobial susceptibility testing (AST) is performed with 4 commonly used antibiotics. The platform achieved 4 h AST with coherent values to Clinical and Laboratory Standards Institute (CLSI) guidelines for minimum inhibitory concentration (MIC) determination. Notably, the modular chip architecture integrates 8 sensing units as a proof-of-concept, coupled with disposable microfluidic chambers that eliminate cross-contamination risks. This chip-calorimeter implementation establishes a new paradigm for chemical reaction heat measurement and rapid clinical diagnostics of infectious diseases.