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Paper-based analytical devices (PADs) offer a low-cost, user-friendly platform for rapid point-of-use testing. Without scalable fabrication methods, however, few PADs make it out of the academic laboratory and into the hands of end users. Previously, wax printing was considered an ideal PAD fabrication method, but given that wax printers are no longer commercially available, alternatives are needed. Here, we present one such alternative: the air-gap PAD. Air-gap PADs consist of hydrophilic paper test zones, separated by “air gaps” and affixed to a hydrophobic backing with double-sided adhesive. The primary appeal of this design is its compatibility with roll-to-roll equipment for large-scale manufacturing. In this study, we examine design considerations for air-gap PADs, compare the performance of wax-printed and air-gap PADs, and report on a pilot-scale roll-to-roll production run of air-gap PADs in partnership with a commercial test-strip manufacturer. Air-gap devices performed comparably to their wax-printed counterparts in Washburn flow experiments, a paper-based titration, and a 12-lane pharmaceutical screening device. Using roll-to-roll manufacturing, we produced 2700 feet of air-gap PADs for as little as $0.03 per PAD.