Saha, S. et al. Nat. Nanotechnol. 10, 645–651 (2015).

Chloride concentrations vary widely within the cytoplasm and organelles, yet existing chloride sensors are typically limited in their range and are sensitive to pH. Saha et al. developed a DNA nanodevice called Clensor that senses chloride levels at all physiologically relevant concentrations in a pH-independent manner. Clensor consists of three nucleic acid–based moieties. The sensing module harbors a chloride-sensitive compound, and the normalizing module with its chloride-insensitive fluorophore allows for ratiometric measurements. In addition, the targeting module can bear different molecules that result in trafficking along the endocytic pathway. The researchers applied Clensor to measure chloride levels in lysosomes of Drosophila hemocytes and to analyze the roles of different chloride channels in endolysosomal compartments.