**6. Conclusions**

Some research groups focusing on microtechnologies have been working toward a high efficiency in vitro fertilization (IVF) process [49] (**Figure 5A**). The IVF goal is to fertilize oocytes, and it consists of several manually or teleoperated manipulation steps that require important practical skills. Sakar et al. [50] developed microtransporters using a simple, single-step microfabrication technique allowing parallel fabrication. They demonstrated that the micro‐ transporters can be navigated to separate individual targeted cells with micron-scale precision and deliver microgels without disturbing the cells in the neighborhood and the local micro‐ environment. Yamanishi et al. [51] presented an innovative driving method, devised for cell sorting, for an on-chip robot actuated by permanent magnets in a chip, where a piezoelectric ceramic is applied to induce ultrasonic vibration to the microfluidic chip and the highfrequency vibration reduces significantly the effective friction on a magnetically driven

Other interesting magnetic microstructures, devised for cell manipulation in in vitro environ‐ ments for LOC applications, but finally eligible in the future for in vivo applications, have been recently proposed. Examples are novel microgrippers, in which both the navigation and the gripper actuation rely on magnetic fields [52] (**Figure 5B**), 3D laser lithography microcages devised to act as cell carriers (**Figure 5D**) [53] or thin magnetic films working at the air fluid

**Figure 5.** Overview of non-conventional manipulation systems for microrobotics and LOC applications. (A) Conceptu‐ al overview of a microfluidic cell manipulation system based on magnetically driven microtools and exploited for oo‐ cytes handling [49] (reproduced with permission from Royal Society of Chemistry); (B) Schematic representation of a remotely controlled microgripper exploiting magnetic fields both for navigation and for gripper actuation (adapted from [52] and reproduced with permission from Royal Society of Chemistry); (C) SEM image of a magnetic thin film devised for cell manipulation (left) and schematic representation of the film structure with microscope images showing T24 cell compatibility with the magnetic structure (right) [13] (reproduced with permission from Springer); (D) SEM image (above) and confocal microscope image of a magnetic microcage after cell culture [53]; (E) Experimental setup for magnetic micromanipulation (left) and microscope images of the magnetic microrobot during christal manipula‐ tion tasks (adapted from [55] and reproduced with permission of the International Union of Crystallography).

microtool.

50 Lab-on-a-Chip Fabrication and Application

LOC technologies represented a real breakthrough in the last decades for in vitro laboratory analyses. However, the integration of really complex functions in a limited space results extremely challenging and further efforts are required to make LOC systems accurate and operating in an automated fashion. Magnetic fields exploitation revealed to be extremely promising and effective in the execution of certain tasks, with the aim of overcoming some of the limitations connected to human operators and enabling procedures impossible with traditional laboratory techniques.

In this sense, the role played by magnetic nanoparticles is extremely important, but alternative techniques providing the samples to be manipulated with magnetic properties have been investigated and show great potentialities.

In some cases, magnetic field-based technologies appear more advantageous compared with other LOC actuation strategies, first of all the fluidic one. However, in view of more reliable systems, a possible future trend, already investigated in many applications focuses on combining several effects, including chemical binding, microfluidic actuation, magnetic and electric fields, to obtain more efficient analytical and biological testing platforms. A further enhancement of LOC devices, and especially of those exploiting magnetic fields, may derive from the integration of technologies that are typical of the microrobotics world. Some examples have been reported in the Section 5.3 and an interesting contribution could derive from microrobotics, both in terms of cell carriers and manipulation systems fabrication, and in terms of control strategies.

The development of cheaper and more reliable LOCs could enable many steps forward in really important fields, such as nanomedicine, personalized medicine, and cellular studies. The advantages and technological progresses offered by magnetic technologies at all the scales and in different fields could surely help to reach this goal.
