The ESSENCE platform is an electrochemical sensor system that utilizes non-planar porous microelectrode microfluidic chips with a fully programmable fluidic/sample system to be a “portable, automatic, rapid, sensitive, and selective” for different emerging contaminants and liquid biopsy. The system is designed with non-planar porous microelectrode interfaces, containing different functional capturing probes for specific sensing tasks. From our previous report, this 3D non-planar structure has advantages such as increased flow’s convective fluxes and disrupts diffusive processes like the electric double layer (EDL). The porous electrode structure utilized the packing material’s higher Zeta potential than the bare glass surface, resulting in the EDL length will be significantly smaller than the clear channel. Due to a smaller EDL length, the relaxation frequency will increase, which shifts the EIS signal to a higher frequency range (1kHz to 100MHz) and results in a fast response with a higher signal-to-noise ratio in Electrochemical Impedance Spectroscopy (EIS) measurements. From the perspective of electric field penetration, the top-down electric direction covers all the packing sensing areas, providing a generally higher electronic signal response than the traditional planar electrode system, leading to a higher signal-to-noise ratio. A second feature from the perspective of microfluidics is the significant fluidic shear force generated due to flow through the porous electrode surface. This higher shear force on the surface can unbind most false-positive signals generated by non-specific binding, such as physical adhesive or biofouling. These unique benefits provide physical enhancements of sensitivity and selectivity without manipulating the chemical material in the system. Earlier we showed that our detection of the biomolecules like DNA (fM sensitivity, which can distinguish against a mismatched DNA), proteins (breast cancer biomarker p53, fM sensitivity, which can distinguish it against another breast cancer biomarker HER2), PFOS (Perfluorooctanesulfonate, 0.5 ng) under the traditional desktop Electrochemical Impedance Spectroscopy (EIS) analyzer in the total process of hourly. In this talk, we have further developed our previous ESSENCE platform to a modular, automatic, and portable, one-stop instrument for clinicians to screen for infectious diseases, liquid biopsy, and toxin detection to detect emerging pathogens while significantly reducing false positives and false negatives, but also decreasing our detecting process to 15 mins in much more hazard background conditions to meet the criteria of POC. Second, A small (15 cm x 17cm) USB programable fluidic/oscilloscope base with a 15 minutes total detecting protocol is applied to our ESSENCE system for a fast Point-of-care (POC) diagnostic. This portable ESSENCE platform can respond to the measurable EIS signals from the oscilloscope with 25 ul samples size (DNA and HER2 proteins in undiluted artificial Urine) with a fully automatic process at the uM to pM regions in 15 minutes. Each ESSENCE chip is also significantly cheaper than the ELISA; the chip costs about $20 (for an academic lab) and can be reused.