Chemometrics and digital image colorimetry approaches applied to paper-based analytical devices: A review

Colorimetric paper-based analytical devices (CPADs) are cost-efficient and high-throughput technologies that use readily available materials for point-of-need (PON) applications by leveraging color changes in response to target analytes. However, the complexity of samples can limit the precision and accuracy of CPAD applications. Therefore, CPADs have been combined with chemometric approaches to enhance analytical performance and provide simple solutions to complex systems. The integration of formal optimization techniques, such as Design of Experiments (DoE), classification tools, quantification methods, and other advanced algorithms enables optimal experimental analytical conditions and extracting meaningful information from the complex colorimetric data generated by CPADs. These approaches facilitate robust calibration and prediction models, enabling reliable quantifications or sample differentiation. In addition, chemometrics combined with CPADs contributes to Green Analytical Chemistry once they have the potential to minimize the number of experiments, provide optimal designs and consumption of reagents, and decrease waste generation. The synergy between digital colorimetry using CPADs and smart devices with chemometric techniques holds great promise for portable analysis in resource-limited settings, with applications ranging from environmental monitoring to point-of-care diagnostics. Herein, we review recent advances in the development of CPADs, ranging from manufacturing methods to extraction of color patterns and data treatment using several chemometric tools, performance assessment, and potential transfer to onsite applications for relevant analytical problems.