In the 1966 movie Fantastic Voyage, a submarine and its crew shrink to the size of a microbe in order to travel into the body of an escaped Soviet scientist and remove a blood clot in his brain. The film gave viewers a glimpse into a possible future where doctors could treat patients by going directly to the source of the problem instead of being limited by the inaccessibility of most parts of the human body. This dream of a tiny submarine that can be piloted through the human body to deliver medical care remains, even 50 years later, in the realm of science fiction. However, Miskin and coworkers at Cornell University have brought us one step closer to making this a reality with their recent development of autonomous microscale machines.
To live up to its name, an autonomous machine must have two features. First, it should be able to detect a stimulus from its environment. Then, without any help or intervention, it must respond to the stimulus with a desired response. In this scenario, the machine is not thinking or making decisions— instead, its response to the stimulus is pre-programmed. The ability to respond without supervision means that it can function in remote, inaccessible places, such as deep inside the human body.
One of the biggest challenges to miniaturizing machines is that they contain moving parts. Even fairly simple mechanisms like hinges and valves are too difficult to make on such a small scale. They would require sub-micron machining precision that is not possible using techniques available today. As a result, scientists and engineers must develop alternative mechanisms to perform the functions of these moving parts.
To address this problem, McEuen and Cohen develop a bimorph actuator— a mechanism that allows the machine to move in response to a stimulus, but does not have any complicated moving parts to fabricate . Instead, the bimorph actuator is just a very thin sheet with two layers, one of graphene and the other of glass, that bends in response to changes in temperature or electrolyte concentration. The glass layer expands or contracts when exposed to the different environmental conditions , but the graphene does not. The expansion or contraction of only one of the layers causes the whole sheet to bend (as shown in Movie S2) . Although glass seems like a material that would break instead of bending, the actuator is only two nanometers thick so it bends easily.
To harness the motion generated by their bimorph actuator, the researchers take inspiration from an old technique: origami. Since the 17th century, origami has been used in Japan to transform flat sheets of paper into three-dimensional sculptures using only a series of folds. With paper origami, the person making the folds knows where they need to go to make the right final sculpture. However, for a micro-machine, these folding instructions must be programmed into the flat sheet during fabrication so it can fold itself. To do this, the researchers attach thick, rigid panels to certain areas of the bimorph sheet, as shown in Figure 1. The sheet is then only able to fold in the areas between the panels, so the folds are constrained by the shapes and locations of the panels. Using this technique, the researchers construct a variety of structures including a helix, a tetrahedron, a cube, and even a book with clasps, as shown in Figure 2.
While a self-folding cube is still a long way from a submarine, this technology does open the door to the development of small machines that function on the cellular level. All of the materials used in the origami micro-machines are biocompatible, so they are non-toxic to cells yet robust enough to withstand the conditions inside the body. The closed structures could potentially be used in the body to selectively deploy a drug in response to a local environment.
With further refinement, these machines have the potential to do more complex things. They are strong enough to support electronics and still be able to fold. In fact, the faces of the folded structures are large enough to contain a microprocessor with about 30 megabits of memory or even a functional radio-frequency identification (RFID) chip. The graphene layer in the bimorph also retains its electrical properties, which may allow for the creation of a network of electrically-connected origami machines that can do more complicated tasks than one machine on its own. So, while these origami machines may be simple, they are a step toward precise sensing and manipulation of matter on the cellular scale and—maybe someday—a microscopic submarine.
 Bimorph, meaning “two-shape” or “two-form”, refers to the two layers of different materials. In this case, one of the materials responds to changes in the environment to produce bending. In general, either one or both materials can be active. Bimorphs are commonly used for actuation, or generating motion, as shown in this paper. They can also be used for sensing by making one of the materials is piezoelectric so it generates a voltage when it bends.
 The ion exchange process is well-known for being able to swell glass and is used commercially to make chemically toughened glass. In certain electrolyte or pH conditions, alkali metal or hydronium ions can diffuse into the voids in the glass and associate with dangling silicon-oxygen bonds. If the ion is larger than the pre-existing void, this causes the glass to swell. Larger ions, such as potassium, result in more swelling than smaller ions like sodium.
 This is the same bending mechanism by which a bimetallic strip can be used in a thermostat. The strip, which is made out of two metals that expand differently due to temperature, is made into a coil whose curvature then depends on the temperature and tells the thermostat when to adjust the temperature and in what direction.