Dual-ratio technique to improve detection depth in diffuse in-vivo fluorescence flow cytometry

Diffuse in-vivo Flow Cytometry (DiFC) is a fluorescence sensing method to detect labeled circulating cells in-vivo non-invasively. The Dual-Ratio (DR) is an optical measurement method that aims to suppress most noise and enhance SNR in deep tissue regions. We investigate DR applied to Near-InfraRed (NIR) DiFC to improve circulating cells' maximum detectable depth and SNR. Results indicate that two critical conditions control the success of DR DiFC. First, the fraction of noise that DR methods cannot cancel (i.e., non-multiplicative factors) cannot dominate. Second, DR DiFC has an advantage regarding SNR if the spatial distribution of tissue autofluorescence contributors is surface-weighted.