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

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100 µm spatial resolution and subsecond temporal resolution at high recovery rates. These performance metrics, which are 100-1000× superior to existing MD approaches, are enabled by a 100× reduction of the microfluidic channel cross-section, a corresponding drastic 100× reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with high spatiotemporal resolution for clinical, biomedical, and pharmaceutical applications.

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

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and in pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100µm spatial resolution and sub-second temporal resolution at high recovery rates. These performance metrics, which are 100X-1000X superior to existing MD approaches, are enabled by a 100X reduction of the microfluidic channel cross-section, a corresponding drastic 100X reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with unprecedented spatio-temporal resolution for clinical, biomedical, and pharmaceutical applications.

Enhancement of faradaic current in an electrochemical cell integrated into silicon microfluidic channels.

Implantable electrochemical sensors enable fast and sensitive detection of analytes in biological tissue, but are hampered by bio-foulant attack and are unable to be recalibrated in-situ. Herein, an electrochemical sensor integrated into ultra-low flow (nL/min) silicon microfluidic channels for protection from foulants and in-situ calibration is demonstrated. The small footprint (5 µm radius channel cross-section) of the device allows its integration into implantable sampling probes for monitoring chemical concentrations in biological tissues. The device is designed for fast scan cyclic voltammetry (FSCV) in the thin-layer regime when analyte depletion at the electrode is efficiently compensated by microfluidic flow. A 3X enhancement of faradaic peak currents is observed due to the increased flux of analytes towards the electrodes. Numerical analysis of in-channel analyte concentration confirmed near complete electrolysis in the thin-layer regime below 10 nL/min. The manufacturing approach is highly scalable and reproducible as it utilizes standard silicon microfabrication technologies.

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

A silicon single-chip microfluidics system that integrates microscale fluidic channels, an analyte segmentation device, and a nozzle for electrohydrodynamic-assisted printing is designed for hyphenation with MALDI mass spectrometry (MS) imaging. A miniaturized T-junction segments analytes into monodisperse picoliter oil-isolated compartments. The printing nozzle deposits generated droplets one-by-one into an array on a conductive substrate without splitting or coalescing. Virtually single-shot MS analysis is enabled due to the ultrasmall droplet volumes and highly localized printing. The signal-to-noise ratio indicates that detection limits at the attomole level are achieved for γ-aminobutyric acid.

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

While droplet microfluidics is becoming an effective tool for biomedical research, sensitive detection of droplet content is still challenging, especially for multiplexed analytes compartmentalized within ultrasmall droplets down to picoliter volumes. To enable such measurements, we demonstrate a silicon-based integrated microfluidic platform for multiplexed analysis of neurochemicals in picoliter droplets via nanoelectrospray ionization (nESI)-mass spectrometry (MS). An integrated silicon microfluidic chip comprising downscaled 7 µm-radius channels, a compact T-junction for droplet generation, and an integrated nESI emitter tip is used for segmentation of analytes into picoliter compartments and their efficient delivery for subsequent MS detection. The developed system demonstrates effective detection of multiple neurochemicals encapsulated within oil-isolated plugs down to low picoliter volumes. Quantitative measurements for each neurochemical demonstrate limits of detection at the attomole level. Such results are promising for applications involving label-free and small-volume detection for monitoring a range of brain chemicals.

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

We report a silicon microfluidic platform that enables monolithic integration of transparent micron-scale microfluidic channels, an on-chip segmentation of analyte flows into picoliter-volume droplets, and a nano-electrospray ionization emitter that enables spatial and temporal separation of oil and aqueous phases during electro-spray for subsequent mass spectrometry analysis.

Exceptional electrocatalytic oxygen evolution via tunable charge transfer interactions in La0.5Sr1.5Ni1-xFexO4±Î´ Ruddlesden-Popper oxides.

The electrolysis of water is of global importance to store renewable energy and the methodical design of next-generation oxygen evolution catalysts requires a greater understanding of the structural and electronic contributions that give rise to increased activities. Herein, we report a series of Ruddlesden-Popper La0.5Sr1.5Ni1-xFexO4±Î´ oxides that promote charge transfer via cross-gap hybridization to enhance electrocatalytic water splitting. Using selective substitution of lanthanum with strontium and nickel with iron to tune the extent to which transition metal and oxygen valence bands hybridize, we demonstrate remarkable catalytic activity of 10 mA cm-2 at a 360 mV overpotential and mass activity of 1930 mA mg-1ox at 1.63 V via a mechanism that utilizes lattice oxygen. This work demonstrates that Ruddlesden-Popper materials can be utilized as active catalysts for oxygen evolution through rational design of structural and electronic configurations that are unattainable in many other crystalline metal oxide phases.