Quartz Crystal Microbalance - micropillar (QCM-P) devices rely on system resonance between the QCM crystal and micropillars directly fabricated on its surface to obtain ultrahigh sensitivity. A numerical model was developed to study the effect of hydrodynamic loadings on a QCM-P device. The effect of substrates with inherent resonant frequencies of 5 and 10 MHz on device performance was also studied numerically. The QCM-P device showed different resonant frequency and amplitude while operated in air or water. As a demonstration of applications of QCM-P in biological detection, a 5 MHz QCM-P device was used to measure acrylic acid grafted on oxygen plasma treated poly(methyl methacrylate) (PMMA) micropillar surfaces. The QCM-P device produced a much higher frequency response than a conventional QCM sensor.