Online and offline preconcentration techniques on paper-based analytical devices for ultrasensitive chemical and biochemical analysis: A review

Microfluidic paper-based analytical devices (mu PADs) have attracted much attention over the past decade. They embody many advantages, such as abundance, portability, cost-effectiveness, and ease of fabrication, making them superior for clinical diagnostics, environmental monitoring, and food safety assurance. Despite these advantages, mu PADs lack the high sensitivity to detect many analytes at trace levels than other commercial analytical instruments such as mass spectrometry. Therefore, a preconcentration step is required to enhance their sensitivity. This review focuses on the techniques used to separate and preconcentrate the analytes onto the mu PADs, such as ion concentration polarization, isotachophoresis, and field amplification sample stacking. Other separations and preconcentration techniques, including liquid-solid and liquid-liquid extractions coupled with mu PADs, are also reviewed and discussed. In addition, the fabrication methods, advantages, disadvantages, and the performance evaluation of the mu PADs concerning their precision and accuracy were highlighted and critically assessed. Finally, the challenges and future perspectives have been discussed.