3D-printed microfluidic nanoelectrospray ionization source based on hydrodynamic focusing

Yu Zhao, Shichang Jiang, Yuna Bai, Xueying Huang, Bo Xiong
2020 Analytical Sciences  
Nanoelectrospray ionization (nESI) mass spectrometry (MS) is an ideal detection for microfluidic chips, and its performances depend on nESI emitters. However, the fabrication of monolithic nESI emitters in chips was difficult. Herein, we propose a three-dimensional (3D) printing method to develop a microfluidic nanoelectrospray ionization source (NIS), composed of a nESI emitter and other components. Firstly, the NIS was compatible with a 50-500 nL min -1 nanoflows by imposing 3D hydrodynamic
more » ... g 3D hydrodynamic focusing to compensate the total flow rate, achieving a 7.2% best relative standard deviation in the total ion current (TIC) profiles. Additionally, it was applied to probe thirteen organic chemicals, insulin, and lysozyme with adequate signal-to-noise ratios and an accuracy of m/z between 9.02×10 -1 and 1.48×10 3 ppm. Finally, the NIS achieved comparable limits of detection compared with its commercial counterpart. Considering the standardized preparation of NIS, it would be a potential option to develop 3D-printed customized Chip-MS platforms. Nanoelectrospray ionization mass spectrometry (nESI-MS) is compatible with micro-and nano-flows, 1,2 and it achieves better sensitivities compared with conventional electrospray MS. 1,3 It has thus been used in various applications, 4,5 including on-line MS detections for microfluidic chips. 6,7 The Electrospray emitter is the key interface between sample flows and mass spectrometers, and it influences the ionization efficiency of nESI sources. However, a facile and standardized method to fabricate monolithic nESI emitters in microfluidic chips is still absent, 8,9 although they could provide near-zero dead volume in on-line chip-MS methods. The preparation of nESI emitters via standardized strategies has ever been tough. Although poly(dimethylsiloxane) 6,10,11 and poly(methyl methacrylate) 12 emitters were reported, glass nESI emitters are the most widely applied, 8,13 and they are generally prepared by chemical etching, 14 heat pulling, 15 or mechanical grinding. 16, 17 However, preceding nESI emitters are with confined configurations. 18 This leads to complex and laborious preparations, 17,19,20 and thus makes these emitters high-cost or fragile. These features, in turn, deteriorated the difficulties to integrate nESI emitters in microfluidic chips. 21, 22 Alternatively, three-dimensional (3D) printing has shown potentials to ease hurdles in preparing nESI emitters. Fused deposition modelling (FDM) is the most widely used 3D printing methods, 23,24 and it constructs 3D spatial objects by deposing melted polymers in pre-specified layers. 25,26 It has been used to prepare different analytical devices, 27,28 including the cartridge for paper-based electrospray ionization, 25,29,30 the ion mobility spectrometer, 31,32 the ion funnel, 33 the spray chamber for inductively coupled plasma spectrometry, 34 and other Analytical Sciences Advance Publication by J-STAGE interfaces. 35, 36 However, its spatial resolution is insufficient to directly prepare nESI emitters with an inner diameter of a few micrometres. 1,2 If its resolution could be compensated, a facile and standardized FDM method would be developed to prepare nESI emitters. The 3D microfluidic hydrodynamic focusing is a potential candidate. It could regulate the distribution of the sample flow by introducing solutions from vertical and horizontal directions. 37-39 It was applied in inhibiting ion diffusion 40 and elevating the accuracy of m/z in chip-MS platforms. 11 If 3D hydrodynamic focusing is imposed to the sample flow, the total flow rate would increase to facilitate nESI with a FDM emitter, and the mixture of sample and focusing solutions would also be inhibited. 40 Herein, a nanoelectrospray ionization source (NIS), consisted of a 3D-printed nESI emitter, a housing case, and connecting components, was developed to achieve a 3D-printed nESI interface in chip-MS platforms. In order to facilitate nESI with a FDM emitter, 3D hydrodynamic focusing was applied to sample flows by imposing horizontal and vertical focusing flows. Moreover, heat drying nitrogen flows were applied to improve the nESI efficiency. In addition, NIS was used to probe organic chemicals and biological macromolecules after various optimizations. Finally, it was compatible with a 50-500 nL min -1 sample flows, and its sensitivities and linear ranges for different samples were investigated. The 3D-printed fabrication of NIS was facile (completely automatically) and low-cost (less than 35 USD). Therefore, the proposed method would be a standardized and user-friendly option to develop chip-MS platforms. Analytical Sciences Advance Publication by J-STAGE
doi:10.2116/analsci.20p219 pmid:33132231 fatcat:odxvk6h2afewlhqxcrbyuqxxr4