In this review, we fundamentally focus on those tools designed for controlled liquid fragmentation.

Among these tools, ow focusing and, in particular, axisymmetric ow focusing with discharge in an open environment (also known as 3D ow focusing and commercially as Flow Focusing ) have provided the most promising combination of mass productivity, control and reproducibility for massive manufacturing of products (mainly, microencapsulated stu) for use in health care and nutrition. A profound revision of the whole uid physics behind that remarkable microuidic tool is also oered, as well as a review of results already obtained in therapeutic applications. 2. Droplet-based microuidics 2.1. Microuidics In a broad sense, microuidics can be regarded as the set of methods, procedures, and techniques designed to precisely manipulate uids which are geometrically constrained to a submillimeter scale. This manipulation includes the production of uid entities such as jets, drops, bubbles, emulsions, and capsules, as well as the motion, arrangement, separation, and mixing of such entities to form more complex uidic structures and induce chemical reactions. The physics of uids on the submillimeter scale is characterized by the importance of viscous forces, diusion, and surface eects. On the contrary, liquid inertia and gravity are generally neglected. Microuidics possesses an enormous relevance in a great variety of elds such as pharmacy, microbiology, chemical engineering, and biotechnology. It may revolutionize in the mid and long-term future several disciplines, including drug discovery and delivery, shifting some of the current paradigms of, for instance, cell biology and tissue engineering. Microuidic technologies fall into two main categories: continuous (often referred to as analogical) and droplet-based (digital) microuidics. The former is based on the manipulation of continuous uid streams across microchannels due to the action of external actuators. These actuators include mechanical pumps, integrated mechanical micropumps, and external pressure sources. One can also resort to combinations of capillary forces and electrokinetic mechanisms such as electroosmosis, electrophoresis, and dielectrophoresis. Continuous-ow microuidics is suitable for simple biochemical applications, including chemical separation. It is less adequate when high degree of exibility or system integrations are required, and lacks high faulttolerance capability. These limitations are partially overcome in droplet10