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

Abstract

A silicon integrated microfluidics system prints picoliter-segmented analytes for attomole-level chemical analysis with mass spectrometry imaging.

Highly Localized Chemical Sampling at Subsecond Temporal Resolution Enabled with a Silicon Nanodialysis Platform at Nanoliter per Minute Flows

“…Segmentation of the dialysate flow into a series of oil-isolated nL-volume droplets was shown to halt this diffusion and helped to reach temporal resolution in the range of just a few seconds. ,− , The drastic reduction of channel cross-section down to 40 μm 2 enabled by our silicon platform and its operation at exceedingly slow nL/min flow rates allows for stable on-chip generation of droplets with volumes as small as just a few pL . We have previously demonstrated an on-chip delivery of such droplets to online mass spectrometry (MS) analysis via an integrated nanoelectrospray ionization (nano-ESI) nozzle or printing them one-by-one for matrix-assisted laser desorption ionization (MALDI) MS, that yield limits of detection (LOD) at the level of just a few attomoles . However, it is envisioned that such drastic reduction of flow rates and analyte volumes will impose a specific challenge of interfacing the segmented flows at the ND chip edge.…”

Highly localized chemical sampling at sub-second temporal resolution enabled with a silicon nanodialysis platform at exceedingly slow flows

“…Integration with previously demonstrated hyphenation of segmented dialysate flows to sensitive MS methods using nano-ESI 29 or MALDI-MS 30 will enable quantification of small molecules at the level of just a few attomoles 31 . The proposed and demonstrated scaling strategy (Fig.…”

“…The drastic reduction of channel cross-section down to 50µm 2 enabled by our silicon platform and its operation at exceedingly slow nL/min flow rates allows for stable on-chip generation of droplets with volumes as small as just a few pL 24 . On-chip delivery of such droplets to online mass spectrometry (MS) analysis via an integrated nano-electrospray ionization (nano-ESI) nozzle 29 or printing them one-by-one for matrix assisted laser desorption ionization (MALDI) MS 30 , we have previously demonstrated limits of detection (LOD) at the level of just a few attomoles 31 . However, such drastic reduction of flow rates and analyte volumes imposes a specific challenge of interfacing the segmented flows at the ND chip edge.…”

Microfluidic Brain‐on‐a‐Chip: From Key Technology to System Integration and Application

“…[34,35] However, thermoplastics are not suitable for long-term cell/tissue culture on chips due to their poor permeability. Silicon [36] has good chemical inertness and thermal stability and can meet the complex 3D structure of chips with high precision, but it is not as good as glass [37] and quartz [38] in terms of electrical insulation and optical transmittance, so the application range is limited.…”