The favorable downscaling behavior of photoacoustic spectroscopy has provoked in recent years a growing interest in the miniaturization of photoacoustic sensors. The individual components of the sensor, namely widely tunable quantum cascade lasers, low loss mid infrared (mid-IR) waveguides, and efficient microelectromechanical systems (MEMS) microphones are becoming available in complementary metal–oxide–semiconductor (CMOS) compatible technologies. This paves the way for the joint processes of miniaturization and full integration. Recently, a prototype microsensor has been designed by the means of a specifically designed coupled optical-acoustic model. This paper discusses the new, or more intense, challenges faced if downscaling is continued. The first limitation in miniaturization is physical: the light source modulation, which matches the increasing cell acoustic resonance frequency, must be kept much slower than the collisional relaxation process. Secondly, from the acoustic modeling point of view, one faces the limit of validity of the continuum hypothesis. Namely, at some point, velocity slip and temperature jump boundary conditions must be used, instead of the continuous boundary conditions, which are valid at the macro-scale. Finally, on the technological side, solutions exist to realize a complete lab-on-a-chip, even if it remains a demanding integration problem.

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