This paper presents an active mechanical perforation method developed for embryo biopsy in the preimplantation genetic diagnosis (PGD) procedure. This mechanical approach utilizes a tungsten micro-needle with a sub-micrometer tip to perform embryo perforation. The micro-needle is driven longitudinally with sinusoidal or square wave signals at frequencies close to the micro-needle bending resonances in order to excite its lateral vibration modes due to nonlinear modal coupling. It has been demonstrated that, in particular, the lateral cutting method, is effective and suitable for embryo perforation as well as microinjection and micro-dissection. A micro-needle driven with a square wave signal at frequency (∼850Hz) close to the micro-needle first bending resonance frequency has been shown to generate an accurate cutting dimensions with minimum damage to the mouse embryo zona pellucida. A success rate of 88 % was achieved based on eight perforation tasks.