Here, we comprehensively investigated methanol electrooxidation on Cu-based catalysts, allowing us to build the first microfluidic fuel cell (μFC) equipped with a Cu anode and a metal-free cathode that converts energy from methanol. We applied a simple, fast, small-scale, and surfactant-free strategy for synthesizing Cu-based nanoparticles at room temperature in steady state (ST), under mechanical stirring (MS), or under ultrasonication (US). The morphology evaluation of the Cu-based samples reveals that they have the same nanoparticle (NP) needle-like form. The elemental mapping composition spectra revealed that pure Cu or Cu oxides were obtained for all synthesized materials. In addition to having more Cu 2 O on the surface, sample US had more Cu(OH) 2 than the others, according to X-ray diffractograms and X-ray photoelectron spectroscopy. The sample US is less carbon-contaminated because of the local heating of the sonic bath, which also enhances the cleanliness of the Cu surface. The activity of the Cu NPs was investigated for methanol electrooxidation in an alkaline medium through electrochemical and spectroelectrochemical measurements. The potentiodynamic and potentiostatic experiments showed higher current densities for the NPs synthesized in the US. In situ FTIR experiments revealed that the three synthesized NP materials eletcrooxidize methanol completely to carbonate through formate. Most importantly, all pathways were led without detectable CO, a poisoning molecule not found at high overpotentials. The reaction path using the US electrode experienced an additional round of formate formation and conversion into carbonate (or CO 2 in the thin layer) after 1.0 V (vs. Ag/Ag/Cl), suggesting improved catalysis. The high activity of NPs synthesized in the US is attributed to effective dissociative adsorption of the fuel due to the site's availability and the presence of hydroxyl groups that may fasten the oxidation of adsorbates from the surface. After understanding the surface reaction, we built a mixed-media μFC fed by methanol in alkaline medium and sodium persulfate in acidic medium. The μFC was equipped with Cu NPs synthesized in ultrasonic-bath-modified carbon paper as the anode and metal-free carbon paper as the cathode. Since the onset potential for methanol electrooxidation was 0.45 V and the reduction reaction revealed 0.90 V, the theoretical OCV is 0.45 V, which provides a spontaneous coupled redox reaction to produce power. The μFC displayed 0.56 mA cm −2 of maximum current density and 26 μW cm −2 of peak power density at 100 μL min −1 . This membraneless system optimizes each half-cell individually, making it possible to build fuel cells with noble metal-free anodes and metal-free cathodes.