Johns Hopkins researchers have developed self-assembling perforated microcubes, designed to deliver targeted in vivo therapy:
The relatively inexpensive microcontainers can be mass-produced through a process that mixes electronic chip-making techniques with basic chemistry. Because of their metallic nature, the cubic containers location in the body could easily be tracked by magnetic resonance imaging.
The method of making these self-assembling containers and the results of successful lab tests involving the cubes were reported in a paper published in the December 2005 issue of the journal Biomedical Microdevices. In the tests, the hollow cubes housed and then dispensed microbeads and live cells commonly used in medical treatment.
To make the self-assembling containers, Gracias and his colleagues begin with some of the same techniques used to make microelectronic circuits: thin film deposition, photolithography and electrodeposition. These methods produce a flat pattern of six squares, in a shape resembling a cross. Each square, made of copper or nickel, has small openings etched into it, so that it eventually will allow medicine or therapeutic cells to pass through.
The researchers use metallic solder to form hinges along the edges between adjoining squares. When the flat shapes are heated briefly in a lab solution, the metallic hinges melt. High surface tension in the liquified solder pulls each pair of adjoining squares together like a swinging door. When the process is completed, they form a perforated cube. When the solution is cooled, the solder hardens again, and the containers remain in their box-like shape.
“To make sure it folds itself exactly into a cube, we have to engineer the hinges very precisely,” Gracias said. “The self-assembly technique allows us to make a large number of these microcontainers at the same time and at a relatively low cost.”
The tiny cubes are coated with a very thin layer of gold, so that they are unlikely to pose toxicity problems within the body. The microcontainers have not yet been implanted in humans or animals, but the researchers have conducted lab tests to demonstrate how they might work in medical applications.
Gracias and his colleagues used micropipettes to insert into the cubes a suspension containing microbeads that are commonly used in cell therapy. The lab team showed that these beads could be released from the cubes through agitation. The researchers also inserted human cells, similar to the type used in medical therapy, into the cubes. A positive stain test showed that these cells remained alive in the microcontainers and could easily be released.