Methods and devices for treatment of biomass comprised of crystalline structures are described that provide a combined mechanical, chemical and thermal effect (i.e., nano-hybrid pretreatment) to synergistically break down the crystalline structures. Such nano-hybrid mixing provides efficient, and cost-effective breakdown which enhances enzymatic accessibility to lignocellulosic materials. Methods and devices shown can be used to produce products such as pulp, chemicals, or biofuels.