A biohybrid microswimmer also known as biohybrid nanorobot, can be defined as a microswimmer that consist of both biological and artificial constituents, for instance, one or several living microorganisms attached to one or various synthetic parts. In recent years nanoscopic and mesoscopic objects have been designed to collectively move through direct inspiration from nature or by harnessing its existing tools. Small mesoscopic to nanoscopic systems typically operate at low Reynolds numbers (Re ≪ 1), and understanding their motion becomes challenging. For locomotion to occur, the symmetry of the system must be broken. In addition, collective motion requires a coupling mechanism between the entities that make up the collective. To develop mesoscopic to nanoscopic entities capable of swarming behaviour, it has been hypothesised that the entities are characterised by broken symmetry with a well-defined morphology, and are powered with some material capable of harvesting energy. If the harvested energy results in a field surrounding the object, then this field can couple with the field of a neighbouring object and bring some coordination to the collective behaviour. Such robotic swarms have been categorised by an online expert panel as among the 10 great unresolved group challenges in the area of robotics. Although investigation of their underlying mechanism of action is still in its infancy, various systems have been developed that are capable of undergoing controlled and uncontrolled swarming motion by harvesting energy (e.g., light, thermal, etc.). Over the past decade, biohybrid microrobots, in which living mobile microorganisms are physically integrated with untethered artificial structures, have gained growing interest to enable the active locomotion and cargo delivery to a target destination. In addition to the motility, the intrinsic capabilities of sensing and eliciting an appropriate response to artificial and environmental changes make cell-based biohybrid microrobots appealing for transportation of cargo to the inaccessible cavities of the human body for local active delivery of diagnostic and therapeutic agents. == Background == Biohybrid microswimmers can be defined as microswimmers that consist of both biological and artificial constituents, for instance, one or several living microorganisms attached to one or various synthetic parts. The pioneers of this field, ahead of their time, were Montemagno and Bachand with a 1999 work regarding specific attachment strategies of biological molecules to nanofabricated substrates enabling the preparation of hybrid inorganic/organic nanoelectromechanical systems, so called NEMS. They described the production of large amounts of F1-ATPase from the thermophilic bacteria Bacillus PS3 for the preparation of F1-ATPase biomolecular motors immobilized on a nanoarray pattern of gold, copper or nickel produced by electron beam lithography. These proteins were attached to one micron microspheres tagged with a synthetic peptide. Consequently, they accomplished the preparation of a platform with chemically active sites and the development of biohybrid devices capable of converting energy of biomolecular motors into useful work. One of the most fundamental questions in science is what defines life. Collective motion is one of the hallmarks of life. This is commonly observed in nature at various dimensional levels as energized entities gather, in a concerted effort, into motile aggregated patterns. These motile aggregated events can be noticed, among many others, as dynamic swarms; e.g., unicellular organisms such as bacteria, locust swarms, or the flocking behaviour of birds. Ever since Newton established his equations of motion, the mystery of motion on the microscale has emerged frequently in scientific history, as famously demonstrated by a couple of articles that should be discussed briefly. First, an essential concept, popularized by Osborne Reynolds, is that the relative importance of inertia and viscosity for the motion of a fluid depends on certain details of the system under consideration. The Reynolds number Re, named in his honor, quantifies this comparison as a dimensionless ratio of characteristic inertial and viscous forces: R e = ρ u l μ {\displaystyle \mathrm {Re} ={\frac {\rho ul}{\mu }}} Here, ρ represents the density of the fluid; u is a characteristic velocity of the system (for instance, the velocity of a swimming particle); l is a characteristic length scale (e.g., the swimmer size); and μ is the viscosity of the fluid. Taking the suspending fluid to be water, and using experimentally observed values for u, one can determine that inertia is important for macroscopic swimmers like fish (Re = 100), while viscosity dominates the motion of microscale swimmers like bacteria (Re = 10−4). The overwhelming importance of viscosity for swimming at the micrometer scale has profound implications for swimming strategy. This has been discussed memorably by E. M. Purcell, who invited the reader into the world of microorganisms and theoretically studied the conditions of their motion. In the first place, propulsion strategies of large scale swimmers often involve imparting momentum to the surrounding fluid in periodic discrete events, such as vortex shedding, and coasting between these events through inertia. This cannot be effective for microscale swimmers like bacteria: due to the large viscous damping, the inertial coasting time of a micron-sized object is on the order of 1 μs. The coasting distance of a microorganism moving at a typical speed is about 0.1 angstroms (Å). Purcell concluded that only forces that are exerted in the present moment on a microscale body contribute to its propulsion, so a constant energy conversion method is essential. Microorganisms have optimized their metabolism for continuous energy production, while purely artificial microswimmers (microrobots) must obtain energy from the environment, since their on-board-storage-capacity is very limited. As a further consequence of the continuous dissipation of energy, biological and artificial microswimmers do not obey the laws of equilibrium statistical physics, and need to be described by non-equilibrium dynamics. Mathematically, Purcell explored the implications of low Reynolds number by taking the Navier-Stokes equation and eliminating the inertial terms: μ ∇ 2 u − ∇ p = 0 {\displaystyle {\begin{aligned}\mu \nabla ^{2}\mathbf {u} -{\boldsymbol {\nabla }}p&={\boldsymbol {0}}\\\end{aligned}}} where u {\displaystyle \mathbf {u} } is the velocity of the fluid and ∇ p {\displaystyle {\boldsymbol {\nabla }}p} is the gradient of the pressure. As Purcell noted, the resulting equation — the Stokes equation — contains no explicit time dependence. This has some important consequences for how a suspended body (e.g., a bacterium) can swim through periodic mechanical motions or deformations (e.g., of a flagellum). First, the rate of motion is practically irrelevant for the motion of the microswimmer and of the surrounding fluid: changing the rate of motion will change the scale of the velocities of the fluid and of the microswimmer, but it will not change the pattern of fluid flow. Secondly, reversing the direction of mechanical motion will simply reverse all velocities in the system. These properties of the Stokes equation severely restrict the range of feasible swimming strategies. Recent publications of biohybrid microswimmers include the use of sperm cells, contractive muscle cells, and bacteria as biological components, as they can efficiently convert chemical energy into movement, and additionally are capable of performing complicated motion depending on environmental conditions. In this sense, biohybrid microswimmer systems can be described as the combination of different functional components: cargo and carrier. The cargo is an element of interest to be moved (and possibly released) in a customized way. The carrier is the component responsible for the movement of the biohybrid, transporting the desired cargo, which is linked to its surface. The great majority of these systems rely on biological motile propulsion for the transportation of synthetic cargo for targeted drug delivery/ There are also examples of the opposite case: artificial microswimmers with biological cargo systems. Over the past decade, biohybrid microrobots, in which living mobile microorganisms are physically integrated with untethered artificial structures, have gained growing interest to enable the active locomotion and cargo delivery to a target destination. In addition to the motility, the intrinsic capabilities of sensing and eliciting an appropriate response to artificial and environmental changes make cell-based biohybrid microrobots appealing for transportation of cargo to the inaccessible cavities of the human body for local active delivery of diagnostic and therapeutic agents. Active locomotion, targeting and steering of concentrated therape
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