The goal of this project is to develop new rapid diagnostic tests (RDTs) for malaria. These tests will have >10-fold improved sensitivity relative to existing alternatives, while remaining low-cost, robust under challenging field conditions, and conservative from a manufacturing and regulatory standpoint. Malaria kills more than 600,000 people per year, most of them children. Effective treatment requires a diagnosis that distinguishes malaria from other illnesses with similar symptoms and correctly identifies the malarial strain. Lateral flow assays (LFAs), the technology used in rapid COVID tests, are widely used for malaria diagnosis because they are simple, inexpensive, and well suited to low-resource settings. As a result, approximately 400 million malaria LFAs are used each year. Unfortunately, malaria LFAs struggle to achieve the sensitivity needed to detect a substantial fraction of malaria infections. A ~10-fold improvement in sensitivity relative to existing alternatives is urgently needed to support the global effort to eliminate deaths from malaria. The limited sensitivity of malaria RTDs stems in large part from limitations inherent in the design of existing LFAs. In an LFA, a target antigen protein first binds to a microscopic gold nanoparticle, and is then captured at the test line in the device; capture of the nanoparticle produces the familiar red line seen on at-home COVID tests. However, basic physical limitations mean that, at best, only about 1 in 100 target antigens are detected this way, with the remaining 9,999 sweeping past the test line undetected. Our multidisciplinary team will combine expertise in malaria treatment, computational protein design, and fundamental principles from chemical engineering to increase this capture efficiency >10-fold. The resulting improvement in test sensitivity is predicted to enable sensitive and specific detection of asymptomatic malaria cases, an urgently needed advance for ongoing efforts to reduce transmission and prevent repeated infection. Importantly, our solution is designed to function as a drop-in replacement for the antibodies used in existing LFAs, which should support rapid adoption using established manufacturing and regulatory infrastructure.