Micro-cantilevers are very effective and reliable devices for bio-sensing applications. In this work, a novel biosensor based on micro-cantilever array was designed, simulated and optimized for different bio-sensing applications with high sensitivity, high accuracy, high throughput, and high Q factor. A truss structure designed in the anchored end of the micro-cantilever which was effective in improving the sensitivity to increase detection accuracy. Also, the effects of the surrounding medium are minimized by this structure to achieve high Q factor and longer vibration for bio-sensor. All the results are compared by the conventional micro-cantilever. As a result, the Q factor is increased from 52.1 to 126.1 within water medium and from 51.8 to 120 within ethanol medium. The actuation of novel MCL is simulated by different piezoelectric materials, the results proof that the amplitude of displacement for the PZT-5H is more efficient than AlN.