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This detector is a prototype of a new modular design for a liquid argon time-projection chamber (LArTPC), comprising a two-by-two array of four modules, each further segmented into two optically isolated LArTPCs. The 2x2 Demonstrator features a number of pioneering technologies, including a low-profile resistive field shell to establish drift fields, native 3D ionization pixelated imaging, and a high-coverage dielectric light readout system. The 2.4-tonne active mass detector is flanked upstream and downstream by supplemental solid-scintillator tracking planes, repurposed from the MINERvA experiment, which track ionizing particles exiting the argon volume. The antineutrino beam data collected by the detector over a 4.5 day period in 2024 include over 30,000 neutrino interactions in the LAr active volume\u2014the first neutrino interactions reported by a DUNE detector prototype. During its physics-quality run, the 2x2 Demonstrator operated at a nominal drift field of 500 V\/cm and maintained good LAr purity, with a stable electron lifetime of approximately 1.25 ms. This paper describes the detector and supporting systems, summarizes the installation and commissioning, and presents the initial validation of collected NuMI beam and off-beam self-triggers. In addition, it highlights observed interactions in the detector volume, including candidate muon antineutrino events.<\/jats:p>","DOI":"10.3390\/instruments10010018","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T10:17:44Z","timestamp":1773742664000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Operation of a Modular 3D-Pixelated Liquid Argon Time-Projection Chamber in a Neutrino Beam"],"prefix":"10.3390","volume":"10","author":[{"given":"S.","family":"Abbaslu","sequence":"first","affiliation":[{"name":"Institute for Research in Fundamental Sciences, Tehran, Iran"}]},{"given":"A. 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