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Hydrogen can be stored and distributed by injecting into existing natural grids, then, at the user site separated and used in different applications. The conventional technology for hydrogen separation is pressure swing adsorption (PSA). The recent NREL study showed the extraction cost for separating hydrogen from a 10% H2 stream with a recovery of 80% is around 3.3–8.3 US$/kg. In this document, new system configurations for low hydrogen concentration separation from the natural gas grid by combining novel membrane-based hybrid technologies will be described in detail. The focus of the manuscript will be on the description of different configurations for the direct hydrogen separation, which comprises a membrane module, a vacuum pump and an electrochemical hydrogen compressor. These technological combinations bring substantial synergy effect of one-another while improving the total hydrogen recovery, purity and total cost of hydrogen. Simulation has been carried out for 17 different configurations; according to the results, a configuration of two-stage membrane modules (in series) with a vacuum pump and an electrochemical hydrogen compressor (EHC) shows highest hydrogen purity (99.9997%) for 25 kg/day of hydrogen production for low-pressure grid. However, this configuration shows a higher electric consumption (configuration B) due to the additional mechanical compressor between the two-stage membrane modules and the EHC. Whereas, when the compressor is excluded, and a double skin Pd membrane (PdDS) module is used in a single-stage while connected to a vacuum pump (configuration A5), the hydrogen purity (99.92%) slightly decreases yet the power consumption considerably improves (1.53 times lower). Besides to these two complementary configurations, the combination of a single membrane module, a vacuum pump and the electrochemical compressor has been also carried out (configuration A) and results show that relatively higher purity can be achieved. Based on four master configurations, this document presents a different novel hybrid system by integrating two to three technologies for hydrogen purification combined in a way that enhances the strengths of each of them. This project has received funding from the Fuel Cells and Hydrogen 2 Joint Undertaking under grant agreement No 700355. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation.