Nanofluidic sensors have been developed over the past decade and demonstrated the capability of sensing single DNA molecules. One important and promising class of nanofluidic devices detects single molecules by inserting a nanopore or nanochannel between two fluid cells and inducing an ionic current by applying an electric bias across the nanopore or nanochannel. When molecules are translocated through the nanopore/nanochannel, a modulation of the baseline ionic current can be observed. In this scheme, the ionic current modulation is approximately the same as the channel resistance modulation, requiring the channel size to be comparable to the molecules to be detected. Here we report on a new sensing scheme to detect the translocation of particles through a fluidic channel, which amplifies the resistance modulation by up to 75 times. In this scheme, the device connects the gate of a MOSFET with a fluidic circuit and monitors the modulation of MOSFET's drain current to detect particles. We demonstrate that amplification can be achieved from both the fluidic circuit and the MOSFET. For a 9.86 μm diameter polystyrene bead that occupies 0.7% of the total volume of the sensing channel, results show that the drain current of the MOSFET is blocked by 30-46%. We also demonstrate the capability of this device to distinguish particles with similar sizes but different surface charges as they translocate through the sensing channel. More interestingly, the experiments with CD4+ T lymphocyte cells show another modulation pattern: the MOSFET's drain current is first enhanced and then blocked, which is not fully understood and needs further investigation. Although at this moment the device is based on microchannels and the particles detected are micron-size beads and cells, we expect that the same scheme can be applied to nanofluidic circuits for single molecule detection.