Critical Coagulation Concentration-Based Salt Titration for Visual Quantification in Gold Nanoparticle-Based Colorimetric Biosensors

In gold nanoparticle (GNP)-based colorimetric biosensors, the gradual color shift is often used to correlate with the concentration of target molecules, and therefore a UV-vis spectrometer is usually required for accurate quantification. Here, we present a critical coagulation concentration (CCC)-based salt titration as a generic and simple way to enable accurate quantification in GNP-based colorimetric biosensors without any analytical equipment. The titration is carried out by stepwise addition of a salt titrant to the premixture of sample and GNPs until the color changes rapidly from red to blue, determined solely by visual inspection. The number of titration steps or the final salt concentration required for a rapid color shift (i.e., CCC) is then used to quantitatively correlate with the concentration of target molecules in the sample. The salt titration-based quantification has been demonstrated with two previously reported GNP-based colorimetric biosensors. Compared with quantification based on the gradual color shift with a spectrometer, the visual quantification based on the rapid color shift in the salt titration eliminates the need for any analytical equipment without sacrificing the performance (i.e., sensitivity and accuracy) and therefore is highly suitable for applications in low-resource settings.