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 mu m spatial resolution and subsecond temporal resolution at high recovery rates. These performance metrics, which are 100-1000x 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 high spatiotemporal resolution for clinical, biomedical, and pharmaceutical applications.