Tiny self-assembling cubes could carry medicine

The focus on building micro and nanosystems with medical applications hold great potential to the degree that microcontainers developed could someday incorporate electronic components.

This would allow the cubes to act as biosensors within the body or to release medication on demand in response to a remote-controlled radio frequency signal.

"We believe these self-assembling microcontainers have great potential as a new tool for medical diagnostics and treatment,"​ David Gracias, an assistant professor in the Department of Biomolecular and Chemical Engineering in the Whiting School of Engineering at Johns Hopkins.

The technique has the added advantage of being relatively inexpensive. The theory is that microcontainers can be mass-produced through a process that mixes electronic chip-making techniques with basic chemistry.

"Our group has developed a new process for fabricating three-dimensional micropatterned containers for cell encapsulation and drug delivery,"​ said Gracias, who led the lab team.

"We're talking about an entirely new encapsulation and delivery device that could lead to a new generation of 'smart pills.' The long-term goal is to be able to implant a collection of these therapeutic containers directly at the site or an injury or an illness,"​ he added.

What is unique is that these tiny cubes are coated with a very thin layer of gold, so that they are unlikely to pose toxicity problems within the body.

To make the self-assembling containers, the researchers used identical techniques to make microelectronic circuits: thin film deposition, photolithography and electrodeposition.

Each square structure has small openings etched into it, so that it eventually allows medicine or therapeutic cells to pass through.

The researchers used metallic solder to form hinges along the edges between adjoining squares. When the flat shapes are heated in a lab solution, the metallic hinges melt.

High surface tension in the liquified solder pulls each pair of adjoining squares together.

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."​

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.

At the Johns Hopkins School of Medicine's In Vivo Cellular and Molecular Imaging Centre, researcher Barjor Gimi and colleagues then used MRI technology to locate and track the metallic cubes as they moved through a sealed microscopic s-shaped fluid channel.

This demonstrated that physicians would be able to use non-invasive technology to see where the therapeutic containers go within the body.

Some of the cubes (those made mostly of nickel) are magnetic, and the researchers believe it should be possible to guide them directly to the site of an illness or injury.

The researchers are now refining the microdevices so that they have nanoporous surfaces. Gimi, whose research focuses on magnetic resonance microimaging of cell function, envisions the use of nanoporous devices for cell encapsulation in hormonal therapy.

He also envisions biosensors mounted on these devices for non-invasive signal detection.

The method is reported in a paper published in the December 2005 issue of the journal Biomedical Microdevices.​