A method for the selective elevation and separation of tissues comprised of multiple layers and a surgical instrument for performing the method. The method may be performed without the requirement of a solid mechanical device insertion or transection through the mucosal layer. In particular, the method and surgical instrument may be used for the selected separation and/or resection of selected portions of benign or malignant tissues (e.g. defining tissue planes, polyp elevation and removal, submucosal tissue tunneling, endoscopic mucosa resection, etc).