All forms of microscopy that have previously been developed rely on classical sources of light, which are relatively noisy by virtue of the photons arriving randomly in time and position. We propose a new technique of two-beam optical microscopy using a nonclassical light source comprising entangled photon pairs generated by the process of nonlinear optical parametric downconversion. Entangled-photon microscopy (EPM) has the potential for providing a substantial improvement over confocal laser scanning fluorescence microscopy (CLSM) as well as over two-photon laser scanning fluorescence microscopy (TPLSM). The latter technique relies on the proportionality of the two-photon absorption rate to the square of the optical photon-flux density, and makes use of a highly focused optical beam to localize the region from which fluorescence is observed. However, because the arrival of pairs of photons is accidental in TPLSM, relatively large values of the photon-flux density are required to achieve photon coincidence and hence absorption. This can lead to undesired phototoxicity and photobleaching of the specimen. EPM, in contrast, relies on the presence of highly correlated photon pairs, which enhances the two-photon absorption rate significantly and enables lower values of the photon-flux density to be used. The process depends linearly, rather than quadratically, on the photon-flux density. Further, the EPM interaction region can be controlled by the use of two beams, providing increased flexibility in the selection of desired regions of a specimen, and leading to enhanced axial and lateral resolution.
Teich et al. (Thu,) studied this question.