Silicon-based microfabricated droplet-microfluidics electrospray emitter for neurochemical sensing


Dynamic chemical heterogeneity of the nervous system is essential to numerous physiological processes. The detection of neurochemical concentration transients is therefore a prerequisite for better understanding the functionality of neural circuits and for implementing strategies for treatment of neural disorders. Currently, the analysis of real-time response of neural circuitry to chemical signaling is hindered by a lack of approaches that enable the chemical composition of brain extracellular space to be detected with sufficient time and chemical resolutions, because of the low basal concentration level of many neuromodulators of interest and chemical dispersion problem during chemical delivery. In this dissertation, a silicon-based miniaturized integrated microfluidic device has been developed for time-resolved detection of neurochemicals with improved chemical sensitivity and selectivity. To alleviate chemical dispersion problem and improve time resolution, analytes are first segmented into ultra-small droplets of volume down to picoliters. Diffusion is confined to a single droplet containing the interface and thereby dispersion is minimized. To this end, a detailed study has been implemented for picoliter-scale droplet generation on chip, so as to achieve satisfactory droplet properties in a stable and reliable manner. Next, to tackle the demanding challenge for sensitive detection of limited amount of analytes encapsulated within picoliter-scale compartments, an integrated Nano-Electrospray Ionization (nESI) emitter has been designed on chip for interfacing of analyte segmentation with online detection by mass spectrometry. By optimizing the emitter design, it was validated that the developed silicon nESI system could realize multiplex detection of various neurochemicals, including Dopamine (DA), Acetylcholine (Ach), Norepinephrine (NE), Serotonin (5-HT), Adenosine (Ado) and Gamma-aminobutyric acid (GABA), with limit of detection as sensitive as attomole level. Further study on nESI tip geometry demonstrates ability of spatial and temporal separation of electrosprayed oil and aqueous phases of the segmented flow, which could potentially further improve the performance of detection by alleviating interference from carrier oil phase. The optimized microfabrication and packaging recipe has been developed to enable precise definition of miniaturized geometrical features of each function module aforementioned and monolithic integration of all modules into single chip, including down-scaled silicon microfluidic channels, miniaturized T-junction droplet generator, and on-chip nESI emitter for efficient ionization and delivery of analytes to subsequent online mass spectrometry analysis. Such microfabricated integrated silicon-based platform demonstrates sensitive detection of segmented neurochemical contents, which would be a powerful tool for neuroscience study in future.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

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