text: Diabetes mellitus is one of the major health care problems in the world. It affects 16 million people in the United States and over 100 million people worldwide. More frequent monitoring of blood glucose can prevent many long-term complications associated with diabetes. Although finger-stick testing is currently available for blood glucose monitoring, the nature of this test restricts its utility for maintaining a strict level of blood glucose. This has resulted in a worldwide effort to develop noninvasive methods for fast, painless, and convenient monitoring of glucose.
  Most biosensors use proteins, which provide the desired analytic specificity, but often are not appropriate for noninvasive detection because they lack an intrinsic signal transduction mechanism. A variety of glucose binding proteins have been isolated and well characterized. These proteins are highly specific for glucose binding, but do not provide any optical signal in the visible region upon glucose binding.
  To date, glucose biosensors are pH sensitive, and will not work properly in certain in vivo applications, where the pH can vary with the metabolic activity of the cell. In addition, the glucose binding proteins used to develop the biosensors have a high glucose affinity not suitable for detecting physiological concentrations of glucose.
  Therefore, there is a need for pH-insensitive glucose biosensors with intrinsic signal transduction mechanisms to provide non-invasive methods of monitoring a wide range of glucose concentrations in vivo.