Diagnosis and therapy of small subsurface tumors of breast is rendered difficult by: a) their small size, b) their particular signatures of genetic expression, and c) the difficulty of delivery of therapeutics, specifically to the tumor site. This research and development is directed towards the development of Near Infrared (NIR) localizer (+/-1mm) for tumors that can be 3 or more cm below the surface of the skin and a few mm in diameter. The convergence of two quantities into a single instrument is proposed to achieve these goals. First, with respect to imaging at high localization, the phase interference method (phased array cancellation) has now been developed to the point where a line of sight to the model cancer tissues has been perfected to a pointing accuracy of +/-1mm for a 3cm subsurface object containing 2) sub-nanomolar amounts of a cancer seeking fluorochrome. The device is comprised of a pair of monochromatic light sources suitable for excitation of fluorescence of the particular molecular beacon, i.e., usually at 780nm, and an equidistant single detector for measuring the phase imbalance detected by a secondary filter usually at 830nm. This detector senses phase inequality of the two anti-phase signals with an output at a null of 90 degrees (the mean value of the phase from the 2 sources). A small object will displace the phase null from 90 degrees by a significant amount (up to 20 degrees phase shift per mm displacement of a small object from the null plane of the phased array). Such displacement is to be read from the numerical indicator of the hand-held phased array scanner. In cases where no other localizer is available for biopsy, the line of sight provided by this instrument could be used as a biopsy guide providing the positional information from several sites. Further applications to head and neck cancer and brain cancer are outlined. It is predicted that this hand-held ergonomic battery operated 2-D tumor localizer will be a prototype in the new family of hand-held disease detection devices that afford fast, real time, accurate detection of subsurface pathologies such as molecular beacon labeled cancers, etc., therefore, technical transfer has already been outlined and a wide market may be established.
