The objective of this article is to report the modeling and optimization of a new MEMS-based phosphonate sensor that utilizes a porous membrane between a gas and a liquid stream to allow operation at low-liquid and high-gas flow rates. Previous work from our laboratory demonstrated that phosphonate molecules can be detected with such a device, but the sensitivity was insufficient for certain applications (e.g., detection of pesticides in foodstuffs). In this article, COMSOL simulations and design of experiments were used to optimize the device. We find that both the simulation and the experiment show that (i) the size of the pores in the membranes and (ii) the liquid channel height make the most difference to the sensor response. Also, by optimizing the geometry, the sensitivity of the device could be enhanced. The optimized device can detect 10(9) molecules with good signal to noise. (C) 2009 American Institute of Chemical Engineers AIChE J, 56: 241-247, 2010