# 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  
In order to fulfill movement and operation of a nanorobot, it depends on the driving components, and there are two driving modes for nanorobots: passive drive and active drive [22]. The former is used at body entry and in nanorobot control, while active drive uses an onboard molecular motor, electric nanomotor, pumps, or a membrane to power the nanorobot [58]. Energy dissipates in the process of moving, running, and transmitting information; therefore, the guarantee for the task is adequate energy supply, and this conflicts with the nanorobot size limit. Internal sources of energy include microchemical cells and converted forms such as fuel cells, ATP motors, etc. External sources are further of two types wherein one dissipates energy in the form of current or light through contact, and the other involves the conversion of external energy through a converter onboard [22]. There have been many attempts to build autonomously propelling robotic machines using motor proteins. Still, their implementation has been limited due to the characteristic unstable nature of protein in the diverse environment [59]. Self-propelled micro/nanomachines available in different types, such as motors, engines, robots, and swimmers, ensure a broad scope in various medical fields. However, sensing, controlled delivery and release, biocompatibility, and propulsion are considered significant challenges in biological applications [60]. Factors that are determined by surface area, such as rate of energy dissipation, become significantly important and limiting when considering its capacity to store fuel. Therefore, nanorobots must be able to harness energy from the external environment for their movement; for this reason, they have been developed in a variety of shapes (with spherical, helical, or asymmetric geometries). Depending on the force required for driving, the propulsion mechanism can be divided into two groups: fuel-based propulsion and fuel-free propulsion. Factors such as fabrication, scale-up, and cost would be pivotal in making these nanorobots commercially available [60]. [PERSON] et al. demonstrated a nanoscale train using motor protein, which was inspired by the movement of the motor protein by the skeleton of the cell [61]. The opening and closing of an actuator were achieved by using DNA components and fuels; this was demonstrated by [PERSON] et al. [62]. The NC Seeman group built a spinning motor and the first biped nanorobot using DNA strands [63]. The University of Cornell's [PERSON] group utilized special material to bind nickel nod to the ATP molecule, whereby the rotor rotates eight circles per second as the ATP hydrolyzes and the driving force and motion are achieved [38]. Cilia and flagellum were natural engines for the [PERSON] nanobot group, which built the smallest synthesis engine in 2003 with a diameter of 500 nm [64]. Microrobots were proposed for use in biomedical applications such as minimally invasive procedures, targeted delivery of drugs, or in vitro cell manipulation and character ization [24]. Many of these applications place micro-devices in a fluidic or soft environment; therefore, it is appropriate to examine the methods of locomotion found in nature at the microscale for inspiration while constructing these microrobots [61; 62; 65]. Four different concepts for propulsion are shown in Figure 2. Comparison between different propulsion techniques with respect to speed is provided in Table 2.  
The Technical University of Munich (TUM) has developed a new electric propulsion system for nanorobots. The propulsion method is based on the fact that DNA molecules carry negative charges. Electric fields can thus be used to move proteins that theoretically allow DNA nanobots to be guided by electrical fields [66]. The tiny robots are fixed with glowing molecules to their small arms. The alternate movement of light points back and forth was observed by Prof. [PERSON] using a fluorescence microscope. The direction of light points was controlled by a simple mouse click [66].