Tissue-based biosensors

Biosensors based on tissue structures in living animals can be used to detect and measure hormones, drugs, and toxins. The potential use of tissue-based biosensors extends to such diverse fields of biomedical science as physiology, pharmacology, and biodefense. In general, tissue-based biosensors can be formed from genetically modified cells or by direct genetic modification in order to introduce biosensor proteins into a tissue in the animal. Biosensor cells transduce the concentration of the molecule being detected into a physical signal, which can be precisely measured. Biophotonics provides the most versatile basis for tissue-based biosensors. Light output from biosensor cells can be in the form of fluorescence or bioluminescence, and, of these two, bioluminescence offers advantages of not requiring an input source of light and having a more favorable signal to noise ratio in living animals than fluorescence. Protein-protein interactions can be used to detect almost any molecule, by means of fusion proteins that can be used to generate resonance energy transfer. Bioluminescence resonance energy transfer (BRET) has the potential to be used for the measurement of a wide variety of molecules in living animals. Two examples are discussed here: a tissue-based biosensor for the hormone vasopressin, and a biosensor for rapamycin, both based on BRET. The possible extension of tissue-based biosensors to human subjects will require solutions to several problems, particularly the mode of detection of the physical output, and demonstration of the safety of the genetic modifications needed to introduce biosensor proteins into cells in vivo.