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Changes, increase or decrease, in the body fluid are passively detected by using a single pixel, non-linear blind de-mixing procedure, which can be extended to general biomedical measurement and diagnosis instruments. More specifically, the single pixel, non-linear blind de-mixing procedure in applied on the hot spots of rheumatic arthritis or breast cancer detection problem using passive two-color infrared imaging, as well as to passively detect blockages in the body fluid circulatory system that might be of importance for coronary artery bypass surgery, diabetes and deep vein thrombosis. Other applications of the mentioned algorithm include a pair of cameras for video, a pair of antennas for cell phones, and in situ data gathering or imaging using multiple mode fiber-optical sensing, as well as selective amplification hearing aids through two-ear binaural processing for de-noise echo cancellation and signal classification.