One of the most exciting new types of biomarkers is the quantum dot – a semiconductive crystal that glows when excited. They are becoming a viable adjunct to fluorescent dyes in bio-imaging applications. Quantum dots work on the principle of the exciton, which is a particle composed of an electron and an electron hole – a position on a crystal lattice where an electron could reside, but doesn’t. The excitons in a quantum dot cannot move freely in three-dimensional space – they are “confined”. This gives quantum dots properties that are a mix of those from bulk semiconductors and discrete molecules.
The electronic properties of a quantum dot relate directly to its size and shape. Smaller crystals have what are called large band gaps, which is the energy difference between two bands of electrons in a lattice. The first type of electron band, the valance band, contains electrons bound to individual atoms. The second type, the conduction band, is made up of electrons that can move freely around an atomic lattice. The energy separation between the two bands is the band gap, which is inversely related to the size of a crystal lattice. The gap acts as an insulator between the two electron bands. The more insulation (i.e. the larger the band gap), the more energy is needed to excite a crystal, and the more energy released when the crystal returns to its resting state.
In fluorescent dye applications, larger band gaps (from smaller crystals) mean higher frequencies of emitted light. Smaller crystals experience a blue-shift in emitted light relative to larger crystals. By controlling the size of crystals, researchers can finely tune the wavelength of light that will be emitted by a particular quantum dot. This is one way in which quantum dots are superior to organic dyes. Quantum dots are also much brighter than fluorescent dyes and are less prone to photo-bleaching – the destruction of a fluorescent particle by photochemical factors. Quantum dots are 20 times brighter and 100 times more stable than fluorescent biomarkers. The only drawback, a minor one, of quantum dots is that they can exhibit irregular blinking, which is related to the radioactive profile of the quantum dot. The frequency of the blinking is completely random.
By using relatively stable quantum dots, scientists can construct highly-detailed three-dimensional images, and can track the movement of molecules and cells in real-time. By binding quantum dots to antibodies, peptides or nucleic acids, researchers can target specific cell proteins for long periods of time. For instance, mice with quantum-dotted lymph nodes “lit up” for over four months. In test tubes, quantum dots allow scientists to see the movements of cells and cell components in developing tissues. Other biological uses of quantum dots may include cancer treatment – targeting tumors, for instance. Researchers have to ensure that quantum dots are not toxic when introduced into a living host or a test-tube culture. They have found it important to restrict ultraviolet light in order to control the release of cadmium from small crystals that contain cadmium.