A new microchip created as a prototype by researchers at the Massachusetts Institute of Technology (MIT, Cambridge; 617-258-5402), can store and release different chemicals on demand from tiny reservoirs built into its silicon structure. When a small electrical voltage is applied to a reservoir, the thin gold cap covering it dissolves, releasing the chemical inside. The microchip could be used for drug delivery, diagnostics, and consumer applications.
In the new chip, a reservoir is opened by applying a small electrical voltage between the reservoir's gold cap (the anode) and another gold structure (the cathode), which causes a current to flow between the two. The cathode remains intact during this process, but the anode dissolves due to an electrochemical reaction between it and the salt solution in which it is bathed. (The researchers have an idea for a new version of the chip that does not employ any solution.) With the anode cap out of the way, the chemical inside is liberated.
The researchers have demonstrated this for multiple chemicals in separate reservoirs. In other words, they applied a small voltage between a reservoir containing chemical A and a cathode and observed that chemical's release, then at a later time did the same for a reservoir containing chemical B with the same results. They did this for several different reservoirs filled with different chemicals over a period of several hours. This shows that multiple compounds can be released independently from a single microchip device.
The dime-sized prototype contains 34 reservoirs, each the size of a pinprick and capable of holding about 25 nL of chemical in solid, liquid, or gel form. "But there's room for over 1,000 reservoirs, potentially thousands more if you make [the reservoirs] smaller," says Robert Langer, professor of chemical and biomedical engineering at MIT and a co-developer of the microchip. "The reservoirs and microchips could both be made much larger or smaller, depending on the desired application."
The prototype chip-testing apparatus contains 34 wires connecting the circuitry of each reservoir to an external power source. The researchers say that it should be possible to make a device that's completely self contained by fitting the chip with a small battery and a microprocessor. The chip could then be either preprogrammed, triggered by remote control, or activated by an on-chip biosensor to release chemicals.
The chip could also be cheap. "We're making them right now in a research lab for about $20 each," says Michael Cima, professor of ceramic processing at MIT and a co-developer of the chip. "With process optimization and larger batches, I could easily see making them for a few dollars each, or even less."
The microchip was described in the Jan. 28, 1999, issue of Nature. "The Nature paper shows that this basic concept works," Cima says. "The next step is to do the engineering to make this into a real application."
In the field of drug delivery, the microchip would allow doctors to control both the amount of drug that is released and the exact time it is released to a patient. This is a marked improvement over existing implants and patches that continuously deliver drugs to patients. For example, infertility treatments that are delivered through a catheter to the skin every 90 min for weeks at a time could be incorporated into a chip that is implanted under the skin and programmed to release the contents of specific reservoirs at specific times.
The microchips would also advance diagnostic tests. Currently, medical tests are performed by adding precise amounts of chemicals in a precise order to fluids like blood and salivaa process that can take days to produce results. A microchip preprogrammed to release the proper chemicals at the right times and in the right order could be fitted to the end of a probe and swirled in a vial of fluid at the patient's bedside so that it could deliver the results in minutes.
In the realm of consumer products, the microchip could be used as perfume jewelry to release different scents based on the wearer's mood. To do this, a biosensor would detect the salinity of the wearer's skin, and would activate the chip's microprocessor accordingly.
Similarly, "A microchip in TVs could someday release different scents keyed to an advertisement or scene," Langer says. In this case, the chip would be triggered by remote control via a signal sent over the airwaves. "The applications, I think, are unlimited. The question is, which are the best ones?"
The chip was developed by Cima; Langer; John Santini, an MIT graduate student; and Achim Göpferich, an MIT visiting scientist during the early stages of the project. Göpferich is now at the Lehrstuhl Für Pharmazeutische Technologie Universität Erlangen-Nürnberg. The research team was granted a broad U.S. patent covering the microchip technology on Aug. 25, 1998. Two patents are pending: a U.S. patent on microchip fabrication (Santini, Cima, and Langer), and a foreign patent covering all aspects of the microchip technology (Santini, Cima, Langer, and Göpferich).
With a prototype chip in hand, what's next? "We want to do the engineering to make this into a real application," Professor Cima said. "Also, we want to better characterize the gold dissolution process. We're filling in the details right now."
The new microchip was constructed at MIT's Microsystems Technology Laboratory. The work was funded in part by the National Science Foundation.
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