# A Brief Review on Challenges in Design and Development of Nanorobots for Medical Applications
## 2 Challenges in the Design and Development of Nanorobots
### Powering and Navigation
#### 2.3.4 Bio-Inspired Nanorobots  
As explained in previous sections, nanorobots, in general, comprise a frame, and driving, sensing, and control components. These components can either be linked by self-assembly or use external means to validate the connection [22]. Presently, research has shifted towards developing bioinspired nanorobots. Bio nanorobots are composed of various biological components and can perform preprogrammed biological tasks at the cellular level. The nanorobotic system contains structural connections, power sources, or biosensors, and the required elements are DNA, carbon nanotubes, and proteins. At the molecular level, the bio nanorobot moves by transforming chemical energy into kinetic energy. Biomolecular motors are rapid, versatile, and have become popular due to their high molecular recognition and ability to self-replicate [85]. The biggest challenge in developing these miniature machines is establishing a valid connection between organic and inorganic components. The sulfuric and amiC DNA strand can be connected to a VPL engine, and a carbon nanotube with unique hydroxy terminals can also be connected to DNA strands [96]. By clustering a PNA compound with a Single-Wall NanoTube (SWNT), Delft University's [PERSON] group linked hydrophilic DNA strands with SWNT antiwater [97]. It is evident that problems in the fabrication of components lie in the connection of the components, as well as determining the robustness of the system. Aside from these challenges, the pivotal reason for using organic nanorobots is the enormous advantage over their inorganic counterparts; advantages include biocompatibility, self-reproductivity, low maintenance, and reliability [96]. Because of these, nanorobots have been realized through organic methods by using gene strands with nanoparticles and modifying the surface of the machines to the biological environment [98]. An interesting approach was proposed that involved combining natural species, such as microorganisms, with synthetic components to create biohybrid or organism-based motors. By achieving this integration, the required propulsion and responsiveness to external stimuli are fulfilled [60]. Using the propulsion properties of microorganisms, nanorobotic systems were developed. The living bacteria propel the system while the external source of the field drives the system to the targeted areas [85]. The most effective propulsion can be attained by using rotating flagella, which aids in locomotion and also in sensing the changes in temperature and concentration [99]. These flagella are distinguished by their structure, protein composition, and propulsion mechanism. Based on this, there are two types: eukaryotic cells and prokaryotic cells [99]. The latter is made from proteins consisting of thin filaments, and the driving mechanism is carried out by each of these filaments; the former involves cells that bend themselves into microtubules, and they instill back and forth movement to the cells by rotating in a clockwise (CW) or counter-clockwise (CCW) direction. This results in a separation of bundles that swim together before moving on to the next cycle in a process called tumbling [85]. The emergence of these systems prompted many researchers to expand their scope, and the delivery of therapeutics has become efficient with good control and navigation [99]. [PERSON] et al. demonstrated that synthetic components can be used to trap the required bacteria and that these biohybrid micromotors are rapid and tunable [100]. [PERSON] et al. revealed a system comprised of a sperm cell in a magnetic microtube, whereby the system is guided using a magnetic field and propelled forward using the motile cells of the force [101]. [PERSON] et al. developed a biohybrid nanorobot using magnetotactic bacterium and flagellum nanomotors; this robot used human capillaries to target certain locations [102]. The challenge with biohybrid machines is to keep the viable component while also maintaining stable physiological parameters.