Deep tissue sensing of chiral molecules using polarization-enhanced photoacoustics

Chiral molecule sensing is typically performed using techniques like chromatography, electrophoresis, enzymatic assays, mass spectrometry, and chiroptical methods. While polarimetry allows for in vivo sensing up to 1 mm depth using ultraviolet-visible light, it is limited by dominant light scattering beyond this depth. We propose that photoacoustic sensing in the near-infrared II (NIR-II) window can enable deep tissue sensing as acoustic waves scatter less than light. To achieve this, we developed a photoacoustic polarization–enhanced optical rotation sensing (PAPEORS) system, capable of estimating optical rotation from photoacoustic signals and correlating it with chiral molecular concentration for depths up to 3.5 mm. Experiments were conducted using aqueous glucose solutions, naproxen, serum-based glucose samples, and ex vivo chicken tissue. PAPEORS achieved a detection limit of 80 mg/dl while using circularly polarized light with serum samples, demonstrating the potential for deep-tissue chiral molecular sensing. PAPEORS holds promise for in vivo sensing and easy miniaturization using single wavelength.