Droplet-assisted electrospray phase separation using an integrated silicon microfluidic platform

Abstract

We report on a silicon microfluidic platform that enables integration of transparent μm-scale microfluidic channels, an on-chip pL-volume droplet generator, and a nano-electrospray ionization emitter that enables spatial and temporal phase separation for mass spectrometry analysis.

Attomole-Level Multiplexed Detection of Neurochemicals in Picoliter Droplets by On-Chip Nanoelectrospray Ionization Coupled to Mass Spectrometry

“…Although silicon-based microfabrication techniques, including surface micromachining and bulk micromachining methods, 49 have been demonstrated to successfully create probe shank and integrated microfluidics channels, the performance demand for our probe requires greater attention to the fabrication process. 50 First, the probe must be electrically conductive, with the cross-section of the probe tip no larger than 20 × 50 μm 2 , so that the electrical field can be focused and strengthened at the tip to enable efficient nESI. Second, the embedded microfluidic channel diameter should not exceed 15 μm to ensure picoliter droplet generation and maintenance of the mechanical stability of the suspended probe tip.…”

“…To achieve the performance requirements for the probe as noted above, a specially designed process for probe microfabrication was developed, as shown in Figure 1 A, which is based on our recent exploration work on silicon microfluidic platform that enables the separation of oil and aqueous phases during electrospray. 50 The fabrication of the neural probes starts with a degreased double-side polished silicon-on-insulator (SOI) wafer. The choice of SOI wafer should accommodate all requirements for the probe system design.…”

Integrated silicon microfluidic chip for picoliter-scale analyte segmentation and microscale printing for mass spectrometry imaging

“…Owing to a much larger Young's modulus and precise control of microfluidic channels down to a few μm radius, silicon microfluidics provides superior control of the ultralow flow rates in the nL min −1 range critical for maintaining droplet volumes in the picoliter regime 18 and maintaining their monodispersity. 19 To transfer droplets onto a MALDI substrate while preserving their chronological order, various deposition techniques have been reported including contact printing, 20 as well as contactless approaches including electrospray deposition 21 and electrohydrodynamic (EHD) assisted printing. 22 Contact printing enables deposition 13 or formation 23 of picoliter to femtoliter droplets by passing a waterfront through an array of prepatterned hydrophilic sites.…”

“…22 Contact printing enables deposition 13 or formation 23 of picoliter to femtoliter droplets by passing a waterfront through an array of prepatterned hydrophilic sites. Among contactless methods, electrospray ionization has been used to introduce picoliter-scale segmented analytes for MS analysis; 10,19 however, when used for deposition on a MALDI substrate, analytes are aerosolized and ionized in the electrosprayed jet 24 which significantly increases the spread of printed patterns and lowers MS sensitivity. 14 The EHDassisted printing with electric field strength below the formation of the electrospray jet has been demonstrated to produce pL-scale droplets, 25,26 limited, however, to a continuous non-segmented analyte flow.…”

“…Owing to a much larger Young's modulus and precise control of microfluidic channels down to a few μm radius, silicon microfluidics provides superior control of the ultralow flow rates in the nL min −1 range critical for maintaining droplet volumes in the picoliter regime 18 and maintaining their monodispersity. 19 …”