Novel 3D Printing Paper-Based Microfluidic Devices for Paper Spray Ionizations (μPAD-MS) and Chromatography Analysis of Illicit Drugs

A novel 3D-printed paper-based microfluidic device integrated with mass-spectrometry (μPAD-MS) was established herein that allows the ionizations and chromatography. A fine microchannel structure of μPAD with the depth of 100 μm was successfully built via stereolithography 3D printing and multiple digital masks within 1s. The solid structure of μPAD allows continuous mobile phase which extended the spray lifetime until 60 minutes. The device also can be reused up to 5^th cycle and be able to maintain the high-intensity signal (10⁵). Chromatography of the mixture drugs on 1 μL plasma was successfully performed by applying gradient elution mobile phase consisting of 100% acetonitrile and 50% acetonitrile. Hence, three illicit drugs namely methamphetamine, 7-aminonitrazepam, and morphine-3-g successfully separated during the acquisitions, producing a clearly separated peaks signal of the chromatograms. Finally, the detection limits of the three drugs on both water and plasma matrices were obtained resulting in an excellent linearity value (R²>0.99) and a limit up to sub-ng•mL^-1. These results revealed μPAD-MS further simplified the ambient ionization method and significantly improve the sensitivity and specificity of the paper spray.