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Microstructure chews on red blood cells

Microstructure chews on red blood cells

Sandia National Laboratories has developed a Pac-Man-like microstructure with silicon microteeth that open and close to capture red blood cells. The development may impact future genetic research in applications such as mechanized microfluidic devices.

The microjaws fit in a microchannel 20 microns wide-about one-third the width of a human hair. When the jaws close, they trap a red blood cell-one of many being pumped through the microchannel. The jaws, which open and close very rapidly, deform captured cells, and then, in less than the blink of an eye and almost playfully, let the little things loose. The blood cells travel on, regain their former shape and appear unharmed.

"We've shown that we can create a micromachine that interacts at the scale of cells," says Sandia researcher Murat Okandan. "We've created a demonstration tool with very flexible technology that we believe will enable many designs and concepts. This device itself may generate interest from the agriculture or genetic engineering marketplaces."

The ultimate goal of the Sandia device is to puncture cells and inject them with DNA, proteins, or pharmaceuticals to counter biological or chemical attacks, gene imbalances, and natural bacterial or viral invasions. The devices can be mass-produced using computer-chip production techniques.

Because of its constant munching, the device bears a strong resemblance to the computer game hero Pac-Man, which also munched creatures travelling along small channels. In this case, the "upper" teeth of the microdevices slide back and forth in piston-like action across the microchannel to momentarily trap individual red blood cells against the lower teeth.

The cells punctured do not need to be blood cells but could be, say, stem cells-cells which are able to change, given suitable direction such as gene implantation, into many of the tissues of the human body, says Okandan.

The capability to implant materials in cells would have large implications for the multibillion-dollar microfluidic device industry, currently capable of analyzing biofluids but not altering them.

The prototype, patent-applied-for devices offer the possibility of considerable mechanical intervention at the cellular level because they operate rapidly and are so small that many units could operate in parallel in a relatively compact volume. Ten complete units fit in an area smaller than a household electric plug prong, and each microdevice can puncture 10 cells per second.

An immediate goal of Okandan, who developed the device with Paul Galambos, Sita Mani, and Jay Jakubczak, also of Sandia National Laboratories, is to see whether the ruffled red blood cells absorb a fluorescent material the group has already shown the cell naturally rejects.

If the material is readily absorbed, it means that Sandia researchers have created the first reported example of a continuous flow, mechanical cellular-membrane disrupter.

A further but still near-term goal is to replace the microteeth with hollow silicon needles now in development. The needles would rapidly inject DNA, RNA, or proteins (including drug molecules) into living cells at precise points of their anatomies and in large numbers, possibly changing the course of a disease or restoring lost functions.

The depth and precise position of molecular insertion would be controlled by researchers who have located the cell's "sweet spot" by observing effects of the insertions. Hundreds or thousands of units assembled in parallel, puncturing cells at high speed, could quickly create a sizeable supply of enhanced material.

Current methods of cell implantation use electric fields to open cell walls for chemical absorption. A problem with this method, called electroporation, is that it causes an overwhelming proportion of cell populations to die. Other manual methods exist in which genetic material is delivered into cells one-by-one through a very fine pipette-a labor-intensive and specialized process. Sandia's Pac-Man device has the possibility of overcoming both of these problems.

Inexpensive fabrication of the device became possible for two reasons: the unique capabilities of the Sandia MEMS SUMMiT V fabrication process-a sequence of deposition, patterning, and etching steps-used to create complicated micromachines, and the use of silicon nitride to build insulated microchannels in that process. The process uses standard integrated circuit fabrication technology.

For more information about microstructures from Sandia: Enter 535

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