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Biohybrid robots are next revolution that incorporate living organisms into robots to optimize their performances.

Scientists have created robots of all shapes and sizes with increasing complexity in recent decades. Some robots function well on assembly lines, tightening bolts or welding together sheets of metal. Recent years have also witnessed an increased interest in intelligent micro-robots. Due to their small size, micro-robots can simulate the shape and movements of real organisms, allowing for operations that would be otherwise difficult to complete by traditional robots.


For example, during earthquakes, micro-robots can move among ruins for search and rescue; or in medical treatments, they can enter the human veins for minimally invasive surgery.  Miniaturized robots smaller than a millimeter are being developed to be placed in the body to kill cancer cells or heal wounds.


A robot is mainly composed of drivers, control systems, executing mechanics, and sensors. Among them, the driver as the power conversion component of the robot determines its motion patterns and performance. The key to the design and manufacture of micro-robots is the miniaturization of the drivers. Micro-robot drivers can be divided into three categories: traditional rigid drives , flexible material drives, and biomaterial drives


However currently, most robots are relatively rigid machines that make unnatural movements. Traditional rigid drives include hydraulic, pneumatic, and the most commonly used electromagnetic motor. When the size of the driver needs to be reduced to the millimeter-scale or smaller, the manufacturing difficulty of traditional drivers sharply increases, while their output force and power density decrease exponentially (millimeter scale, maximum output force about 10 μN, output power density < 0.01 kW/kg). For instance, the battery-powered fully charged bee-like micro-robot developed by Harvard University can only fly for a few seconds. The hummingbird robot driven by two motors developed by Purdue University can merely fly for 1.23 min at most


Soft robots have little or no hard internal structures.  Unlike rigid robots, soft robots can replicate natural motion – grasping and manipulation – to provide medical and other types of assistance, perform delicate tasks, or pick up soft objects. These driving methods use flexible stimuli-active materials such as dielectric elastomer actuator (DEA), shape memory alloy (SMA), and liquid crystal elastomer (LCE) are developed. Compared with traditional driving methods, this flexible material drive can be powered by electrical stimulation at the millimeter or even smaller scale, and among other advantages, has better self-repair capability and reliability. However, due to the lack of in-depth research on stress, strain, response speed, efficiency, and lifespan, research on flexible material drivers is still in its infancy.  Certain disadvantages, such as low power density and high driving voltage, are still hindering its practical applications.

This next revolution in soft robotics is called biohybrid robots which could be endowed with muscle cells to help them perform subtle movements. And on a microscopic scale, tiny robots could be merged with bacteria to ferry them through the body for precision medical procedures. Recent advances in biofabrication techniques have achieved integration of engineered muscle tissues with artificial devices, leading to biohybrid robots that allow us to understand the design strategy of living organisms and to engineer their dynamic systems.


Biohybrid robots also known as biobots

Compared with the traditional rigid-driven and flexible material-driven robots, biomaterial-driven biohybrid robots (also known as biobots) can better recapitulate the microstructures and motion patterns of living organisms, with remarkable advantages of high controllability, output force, and power density at the millimeter and smaller scales, accompanied by the potential of self-assembly, self-repair, and self-replication capabilities


What’s lacking among all these fascinating robots is the range of fine movement and the energy efficiency found in living organisms, which evolved toward perfection over the course of millions of years, said lead author Leonardo Ricotti, of the BioRobotics Institute at the Sant’Anna School of Advanced Studies, in Pisa, Italy. That’s why it’s necessary to incorporate elements of living organisms into robots to optimize their performances.


Actuation, or the coordination of movement, is a persistent hurdle in robotics, Ricotti said. For example, robots can be designed to easily lift heavy weights or make precision cuts, but they have difficulty coordinating actions as subtle as cracking an egg cleanly into a bowl or caressing a distressed individual. Their initial movements are jerky.

Animal movements, in contrast, start gently on a micro scale as a cascade of molecular machinery becomes activated inside nerve cells, and culminate in large-scale muscular motion, according to the review. This raises the possibility that animal tissue, such as cardiac muscle or insect muscle, could provide precise actuation and steady movement in robots.


An immediate first approach is to use muscle cells to move the robots, replacing motors, gears and cables. Mainly cardiac and skeletal muscle tissues have been used as the muscle tissues for biohybrid robots because their contractions are generated by applying external stimulation, such as electrical and optical  stimulations. Rapid progress in biohybrid robots with skeletal muscle tissues formed on a flexible substrate has enabled various types of locomotion powered by muscle tissue.


For example, a group led by Barry Trimmer of Tufts University, a co-author of the Science Robotics paper, has developed worm-like biohybrid robots that move via the contraction of insect muscle cells. A team from the University of Tokyo has created a robotic finger with a joint that rotates 90° thanks to its rat muscle cells, which researchers have cultivated in the laboratory and placed aligned with one another as in natural fibres, in a pair of muscles that relax and contract antagonistically, as also occurs in living beings. According to the first author of the study, Yuya Morimoto, “using this antagonistic arrangement of muscles, these robots can mimic the actions of a human finger,” something the researchers have demonstrated by picking up and putting down objects with their robotic finger.


Another problem in robotics is the power supply, particularly for micro-robots, in which the powering device can be bigger than the robot itself. Currently, mechanical soft robots that mimic fish and jellyfish propulsion leverage engineered materials. However, these biomimetic robots exhibit higher energy consumption than their animal counterparts and are therefore typically tethered to external power supplies.


In contrast, biological soft robots require less power. Examples of these bottom-up approaches include artificial jellyfish and rays made from rat cardiomyocytes seeded on silicon scaffolds, as well as robots that incorporate skeletal muscle, collagen, and sea slug tissue cultures for additional features, such as speed and controllability. By using live jellyfish as a natural scaffold, we can use the animals’ own basal metabolism to reduce power requirements, leverage its muscles for actuation, and rely on self-healing and regenerative tissue properties for increased damage tolerance.


Sylvain Martel, of Polytechnique Montréal, also a co-author of the Science Robotics paper, is using magnetotactic bacteria, which naturally move along magnetic field lines, to transport medicine to hard-to-reach cancer cells. Martel’s group can direct the bacteria with external magnets.


Muscle cells can also allow biohybrid robots to walk or swim. A team from Harvard University and Caltech created in 2012 a tiny silicone jellyfish coated with rat cardiomyocytes —heart muscle cells— that were contracted to propel it through water. More recently, Harvard researchers have developed a swimming robot in the shape of a ray fish, with a micro-fabricated gold skeleton and a 16-millimetre rubber body that swims by undulating its body by means of 200,000 live rat cardiomyocytes.


Recent development of interdisciplinary subjects in bioengineering, nanotechnology, and three-dimensional (3D) bioprinting, the combination of biological living actuators and nonliving biomaterials became a possible solution for overcoming the limitations of existing driving methods.


Biohybrid robots with unprecedented biomimicry in driving performance can potentially yield great applications in mechanics, biomedicine, material science, chemical engineering, and many other fields.


Types of Biohybrid systems

At present, there are two approaches to building biohybrid systems. The first is to incorporate live
cells or tissues. Ricotti et al. describe this bottomup approach for a comprehensive list of devices actuated by living cells, from bacteria and motile cells, cardiomyocytes, skeletal muscles, and insect self-contractile tissues. These approaches offer advantages, such as increased controllability and new potentials in environmental sensing, but require specific media for survival.


Another approach is to integrate electronics into live insects and higher-order animals. The external control of insect locomotion has incited a growing collection of “cyborg” cockroaches,
beetles, and moths.


The control of aquatic animals has additional potential for robotics. First, as previously described, biohybrid swimming robots can expand ocean monitoring to areas that traditional AUVs and ROVs cannot reach because of size constraints, damage to the vehicle, or impact on the wildlife. Second, using marine invertebrates offers insights into modes of locomotion that arose early in the evolutionary history of animals.


Mammalian cells

Herein, the reference to primary mammalian cells generally means the cell suspension extracted from mammalian organs or muscles, which can form new muscle tissue after tissue culturing. The most commonly used cells of this type are primary cardiomyocytes and primary skeletal muscle cells extracted from newborn mice. The muscle actuators of these two types of cells have been widely used in biohybrid robots due to sufficient developmental plasticity, which allows them to be planted on extracellular materials to form integrated devices.


Primary skeletal muscles

In comparison with the volume of research on primary cardiomyocytes, fewer studies exist on primary skeletal muscle cells. Despite their relatively short lifespan (several hours to a few days), primary skeletal muscle cells do not contract spontaneously, which allows for higher controllability and activities that are more dynamic and complicated. Although biobots driven by skeletal muscles can achieve all kinds of movements, the problem remains that they can only operate in culture medium instead of ambient air.



In addition to biobots driven by muscle cells, microorganisms are also widely used to actuate biobots. Microorganisms have the advantages of small size, low weight, high speed, and high viability. Furthermore, they have the ability to show magnetotaxis, chemotaxis, and responses to other physio-chemical stimuli. Microbial robots can mainly be divided into those driven by microalgae  and bacteria.


In addition to common mammalian muscle cells and DV tissues, many other biomaterials have been studied as driving sources for biological robots, such as sperm cells, macrophages, non-mammalian cardiomyocytes, or muscle tissues of Drosophila larvae.


Low-power microelectronics embedded in live jellyfish enhance propulsion

Jellyfish are compelling model organisms for more energy-efficient underwater vehicles because of their low cost of transport (COT; or mass-specific energy input per distance traveled). Existing robotic mimics of swimming animals composed entirely of engineered components can achieve velocities comparable to natural animals, but with orders of magnitude less efficiency than jellyfish.


In contrast, biohybrid jellyfish robots that incorporate live animals offer potential advantages that address the grand challenges of robotics, by using the jellyfish structure and muscle for actuation, solving the power requirements by leveraging natural feeding behaviors to extract chemical energy from prey in situ, and recovering from damage via wound healing processes that are inherent to the animal.


In addition to the energy efficiency exhibited by natural jellyfish, biohybrid robotic jellyfish offer new advantages to robotics because jellyfish are naturally found in a variety of environments, including thousands of meters below surface (the limit of current ocean exploration depths), which the animals can traverse without a swim bladder for pressure equilibration.


Nicole W. Xu1 and John O. Dabiri  have developed a  biohybrid robot that is 10 to 1000 times more energy efficient than existing swimming robots reported in literature, by integrating microelectronics in live jellyfish. Measurements demonstrate that propulsion can be substantially enhanced by driving body contractions at an optimal frequency range faster than natural behavior. Swimming speed can be enhanced nearly threefold, with only a twofold increase in metabolic expenditure of the animal and 10 mW of external power input to the microelectronics. To attach the swim controller to the jellyfish, Electrodes were inserted bilaterally into the subumbrellar tissue midway between the bell margin and center.


This capability can expand the performance envelope of biohybrid robots relative to natural animals for applications such as ocean monitoring. Because jellyfish are naturally found in a wide range of salinities, temperatures, oxygen concentrations, and depths (including 3700 m or deeper in the Mariana Trench), these biohybrid robots also have the potential to be deployed throughout the world’s oceans. Because biologging larger marine animals has been shown to expand the capabilities of ocean observations , the user control of jellyfish could further expand ocean monitoring and robotic sampling as an additional resource to current work using autonomous underwater vehicles (AUVs)  and hydroacoustics.


Powering artificial muscles

Muscles need electrical stimulation to contract, which in the case of the robotic finger and the Harvard and Caltech jellyfish is supplied by electrodes. However, there are other more desirable options. The researchers who made the rubber ray fish modified the muscle cells through genetic engineering in order for them to be activated with light.


Another option is to activate the muscles by means of the natural electrical stimulation provided in the body by motor neurons, which are specialised in controlling muscle fibres. Researchers have already succeeded in creating in vitro cultures of combined muscle cells and motor neurons similar to the systems of living beings.


They are now applying them to the manufacture of biohybrid robots. Previously, the team led by Saif had created tiny sperm-like robots, propelled by muscle cells that beat autonomously. More recently, the engineer has succeeded in improving the system by introducing motor neurons that power the muscles. The robot, the size of a pinhead, self assembles when researchers cultivate muscle cells and neuronal precursors with the double-tailed synthetic soft body, designed by engineer Mattia Gazzola.


For now, Saif has used neurons that are genetically modified to be activated by pulses of light, but a further step will be to add to the sensory neuron system neurons that are capable of detecting external stimuli and sending signals to motor neurons to activate the muscle; in other words, living machines that respond to their environment and make decisions. “We are developing biohybrid swimmers that can swim along x and y direction and turn, and sense the presence of a mechanical obstacle and avoid it during swimming. They will also be trained for memory and logic,” says the engineer.


“These are the first generation of biohybrid robots,” says Saif. In the future, he says, “they may be used both for medical and environmental purposes for drug delivery in vivo, and for testing drug efficacy. They may be deployed for the detection of toxins in the environment as well as their clean-up.” And on the horizon there is still one more advance on which some researchers are already working: replacing the synthetic materials in the bodies and skeletons of biohybrid robots with others of biological origin, such as collagen. Then we will no longer be talking about robotic engineering, but rather about the engineering of organisms specifically designed for particular missions. As Rossiter predicts, “we are at the start of a new revolution.”


However, such biological robots are limited to swimming in cell medium cultures for survival. There are limits to what these biohybrid robots can achieve, though, Ricotti said. Living cells need to be nourished, which means that, for now, these robots tend to be short-lived. Also, biohybrid robots can operate only in the temperature range suitable for life, meaning that they can’t be used in extreme heat or cold.




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