Sam Sia, a Biomedical Engineering Professor at Columbia Engineering recently led a team that used biomaterials that can safely be implanted in the body to manufacture microscale-sized machines. Engineers have been studying hydrogels (biocompatible materials) for decades and Sia has used these to make devices that have freely moving, three-dimensional parts. He achieved this by inventing a new technique that stacks the soft material in layers.
The team developed a “locking mechanism” for precise movement and actuation of freely moving parts by taking advantage of the unique mechanical properties of hydrogels. This will provide functions such as manifolds, valves, pumps, rotors and drug delivery. The biomaterials were then tuned within a wide range of diffusive and mechanical properties. The team also managed to control them after implantation without having to use a sustained power supply such as a battery. Payload delivery was tested in a bone cancer model. The researchers found that triggering the release of doxorubicin from the device over a 10-day period resulted in high treatment efficacy. Toxicity was also found to be extremely low at 1/10 of the standard systemic chemotherapy dose.
Sia is also a member of the Data Science Institute and explained that their iMEMS platform allows the development of biocompatible implantable micro-devices with an extensive range of intricate moving components. Not only do the devices solve issues of biocompatibility and device powering, but they can also be controlled wirelessly on demand. Sia’s team is really excited because they have been able to connect the world of complex, elaborate medical devices with that of biomaterials. The platform has a huge number of potential applications, which include the drug delivery system demonstrated in their paper. The delivery system is in turn linked to providing tailored drug doses for precision medicine.
Most implantable micro-devices currently available have limited bio-compatibility because they require batteries or other toxic electronics. They also have static components rather than moving parts. Sia’s team has been working on solving these problems for more than eight years. Yin Chin, lead author of the study explains that as hydrogels are soft and therefore not compatible with traditional machining techniques, they are difficult to work with. To overcome this, they have carefully matched the stiffness of structures that touch each other within the device and have tuned the mechanical properties. Gears that interlock for example, have to be stiff in order to withstand repeated actuation and to allow for force transmission. On the other hand, structures that form locking mechanisms have to be flexible and soft to allow the gears to slip by them during actuation. At the same time, they have to be stiff enough to hold the gears in place while the device is not actuated. The team also studied the diffusive properties of the hydrogels to make sure that the drugs that are loaded do not diffused through the hydrogel layers easily.
Light was used to polymerize sheets of gel and to incorporate a stepper automation to control the z-axis. This had the effect of patterning the sheets layer-by-layer, thus creating three-dimensionality. The thickness of each layer was managed throughout the fabrication process, while the team created composite structures within one layer of the hydrogel by controlling the z-axis. Multiple, precisely aligned layers were stacked and, as each layer could be polymerized sequentially, the complex structure was built in less than 30 minutes.
The iMEMS technique used by Sia’s team addresses various fundamental considerations in building biocompatible micro-robots, micro-devices and micro-machines:
- How to make small biocompatible moveable components from a non-silicon material (silicon has limited biocompatibility)
- How to provide power to small robotic devices without using toxic batteries
- How to communicate wirelessly once the device has been implanted (radio frequency microelectronics are not biocompatible, are relatively large, and require power)
The researchers have managed to trigger the iMEMS device to release extra payloads over days to weeks after implantation. Precise actuation was achieved by using magnetic forces to induce gear movements. This in turn bends structural beams made of hydrogels with properties that are highly tunable. Magnetic iron particles are FDA-approved for human use as contrast agents and are commonly used.
The team has tested the drug delivery system on mice with bone cancer with the cooperation of Francis Lee, an orthopedic surgeon at Columbia University Medical Center at the time of the study. Chemotherapy was delivered adjacent to the cancer by the iMEMS system. Tumor growth was limited, while less toxicity was shown than would have been the case had chemotherapy been administered throughout the body.
Sia noted that the microscale components could be used for micro electromechanical systems to create larger devices. Potential applications range from catheters to cardiac pacemakers to drug delivery, and includes soft robotics.
Replacement tissues is already being manufactured, and small implantable devices, sensors, or robots that we can be communicated to wirelessly can now be made. Sia’s iMEMS system could advance progress in the field a step closer to developing soft miniaturized robots that can interact safely with humans as well as other living systems.
The study has been published online in Science Robotics.