Design Of New Micro-probes For ESI And Its Fabrication By Direct Laser Writing

As an essential component of mass spectrometer,the ion source has always been the focus of many researchers.The development of electrospray ionization(ESI)and matrixed assisted laser desorption ionization(MALDI)in the 1980 s that enabled the rapid development of organic biological mass spectrometry.Since then,proteomics and metabolomics acquired a powerful research tool.Compared with the MALDI,the ESI is of higher-throughput,higher ionization efficiency,higher additional charge,and can be easily combined with liquid chromatography,capillary electrophoresis and other liquid phase separation methods to achieve a variety of instruments with different functions.Therefore,the researchers have been focusing on optimizing and improving the ESI devices to obtain higher performance and wider application,which include using smaller size nozzles to achieve higher ionization efficiency and sensitivity,fabricating micro-nozzle arrays to improve the detection throughput and reduce the failure rate,designing improved structure to realize the combination of sampling and ionization(nanospray desorption electrospray ionization,nano-DESI),as well as integrating measures to further improve stability of nano-DESI,etc.However,limited by the complex processing and high fabricating difficulty of traditional micromachining methods,many constructive designs cannot be concreated flexibly and freely.These problems hinder the further promotion and optimization of ESI.Two-photon polymerization direct laser writing(TPP-DLW)is a new micromachining technique with high precision(submicron level),high design degree of freedom and ability of programmable machining.It is a powerful tool for machining complex structures.Thus,this paper presented a method which applying TPP-DLW to the design and fabrication of ESI microprobes,which can be used to design ESI microprobe freely and complete the processing of multiple complex microprobes.It will be a universal processing paradigm for realizing a capillary and multi-energy microprobe.The specific contents of this paper are as follows:(1)Designing and processing of the micro-emitter with multi-nozzles(Chapter 2): a microemitter with multi-nozzles(MEMS)which can be nested with a capillary to form a multinozzles capillary was designed.The micro-emitter consists of a multi-nozzles array and a capillary interface.The number of nozzles can be flexibly adapted in the multi-nozzle array,and the capillary interface can be fitted with the solvent supply capillary.The MEMS were processed by TPP-DLW,and the aperture of the nozzles can be processed to less than 10 μm,the thickness of the edge is less than 2 μm.A method was developed to integrating the MEMS and capillary.This methodology of designing by computer assisted desiging and fabricating by TPP-DLW is more efficient and has a high degree of freedom of machining than traditional micromachining methods,which can provide a powerful tool in ESI optimization research.(2)Processing of the micro-emitter with multi-nozzles processing on non-standard substrates(Chapter 3): in order to further simplify the design and machining process,the capillary interface and the integrating step with the sampling capillary were removed,and a fabricating process was developed to shaping multi-nozzles array directly on the capillary.the MEMS were processed on the capillary with an inner diameter of 75 μm and 150 μm,respectively.The electrospray effect of the capillary with one,eight and sixteen nozzles were compared,and the results indicated that the multi nozzles array can product smaller droplets than single nozzle probe.So,it is suggested that TPP-DLW directly processing new microprobes on the capillary has a satisfying prospect in the research filed.(3)Designing and fabricating of an integrated microprobe with function of sampling and ionizing(Chapter 4): inspired by the design of nano-DESI,a sampling-ionization integrated microprobe with a V-shaped flow channel was designed and fabricated,the solvent flows through one side channel of the V-shaped flow channel,and desorb the sample from the hole at bottom,and then the sample along with solvent is transferred through the other side flow channel and ionized on the tip by electrospray.In order to improve the performance of the integrated microprobe,the integrated microprobes were coupled with novel micro-emitters to achieve various microprobes,those novel microprobes also proved that the superiority of the application of TPP-DLW to improve performance of ESI because of the high degree of processing freedom of the computer design and TPP-DLW processing method.In conclusion,this paper proposes a processing method for designing and processing new microprobes for ESI using TPP-DLW.Owing to the processing characteristics of TPP-DLW,such as high degree of designing and fabricating freedom,this method can combine capillary with different micro-probes to achieve different functions.It can also organically combine different microprobes to achieve variously functional microprobes,which will provide a tool and inspiration for further research and optimization of ESI.