Innovative Biosensors are Being Developed from Silkworm Cocoons

Silkworm cocoons are being used to develop new biosensors that could be inserted into patients and used as a tracking device to monitor their progress after surgery, or track chronic diseases such as diabetes.

Bioengineer Fiorenzo Omenetto, Ph.D., of Tufts University (Medford, MA, USA) is using cocoons spun by the silkworm Bombyx mori to manufacture target-specific biosensors, using specific molds to shape a silk-protein solution extract into optical devices that are patterned with optical nanoscale features. This fine detailing is important in optics, since light interacts best with features at a scale no bigger than its own wavelength--about 400 to 700 nanometers in the case of visible light. Proteins embedded in the optical material efficiently bind to a target such as oxygen or a bacterial protein; when they do, the light transmitted by the sensor changes color. Once integrated into the silk devices, the proteins remain active for years.

One such device is a translucent red card impregnated with hemoglobin and patterned with several optical elements, including a diffraction grating that splits white light into its component colors. The card acts as a simple oxygen sensor: light passing through it changes wavelength slightly, depending on how much oxygen has bound to the embedded hemoglobin. These changes cannot be seen with the naked eye, but can be detected by a photodiode, a device that turns light into electrical current. When a drop of oxygen-rich blood is placed on the sensor the hemoglobin draws in oxygen from it, and the wavelength of light registered by the photodiode shifts. The researchers have also made silk structures containing a volatile horseradish enzyme called peroxidase, as well as a glucose biosensor that could incorporate hexokinase, an enzyme that binds to sugar.

Gratings with antibodies and enzymes embedded in them could sense just about any medically interesting molecule, such as a tumor marker. Another application of the silk optical fibers could be carrying light from the surface of the skin to the implanted sensors and back, so that it can be read by a photodetector. The sensors could be implanted during surgeries such as tumor resections and then used to monitor patients for signs of infection or recurring cancer. The device eventually dissolves harmlessly, along with the rest of the supportive structures. The biosensors were described in an article published in the January-February 2009 issue of MIT Technology Review.

The strongest natural fiber known, silk is favored by tissue engineers because it is mechanically tough but degrades harmlessly inside the body. To manufacture the biosensors, the cocoons are boiled in a solution containing sodium carbonate. This helps dissolve sericin, a gluey glycoprotein that holds the cocoons together but causes immune reactions in humans. After the silk fibers dry, they are dissolved in a solution of lithium bromide. When the solution cools, it is loaded into a dialysis cartridge and set inside a beaker of water, which draws out the salt. What is left is a clear, viscous solution of the purified protein silk fibroin. The silk "syrup" is then removed with a syringe and loaded into a row of test tubes, ready for use in manufacturing the biosensors.

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