ABSTRACT Hepatitis C virus (HCV) infection is a widely prevalent bloodborne infection, with approximately 71 million global (2.4 million in USA) chronic infections worldwide. HCV infection is frequently asymptomatic and many of those infected are unaware of their illness. Untreated HCV infection may lead to chronic liver disease, such as hepatocellular carcinoma, and accounts for an estimated 1.1 million annual global deaths (14,000 USA). Within the last six years, direct acting antivirals (DAAs) have demonstrated high cure rates (90-95%) across all genotypes in less than 12 weeks of all-oral treatment. These highly effective therapeutics offer a path toward ending the HCV epidemic as drugs become more affordable and global health efforts prioritize expanded access. The rollout of DAAs relies on diagnostic testing to identify HCV cases and rapidly link eligible patients to treatment options. In most clinical settings, current HCV testing protocols use a rapid antibody test to diagnose past or current cases of HCV. While rapid HCV antibody tests are easy to use and widely available, current HCV nucleic acid amplification tests (NAATs) require venipuncture blood samples and central laboratories where tests are run by trained technicians on complex, expensive equipment, causing delayed test results and loss to follow-up. Recent initiatives by the Whitehouse White House’s HCV Elimination Program, WHO, MSF Access Campaign, and NIH (NOSI: NOT-AI-23-001) have encouraged the development of point-of-care (POC) HCV NAATs to provide accessible and rapid diagnosis of chronic HCV and aid in the rollout of DAAs. Decentralized, clinic-based HCV NAATs offer a streamlined approach to patient care where a single test may be used to diagnose HCV, identify active viremia, and later confirm a cure. There is an abundance of commercial POC NAAT tests for respiratory diseases, such as influenza or SARS-COV-2, but due to the significant technical challenges of detecting low viral titers in blood samples, there are no available capillary whole blood rapid POC NAATs for HCV that meet target product profiles. We have developed a new approach for an integrated POC NAAT for detecting HCV from whole blood. Our proposed HCV test is a significant departure from most existing POC tests that use classical extraction methods (solid phase extraction), multiple buffer exchanges, reaction chambers, PCR amplification, and robotics for physical actuation to automate and miniaturize laboratory-based PCR workflows. Here, we propose an innovative paper-based device with novel whole blood sample preparation and electrophoretically-mediated RNA purification, amplification, that is capable of simultaneously extracting and amplifying viral HCV RNA from whole capillary blood using reverse transcription recombinase polymerase amplification. The test cartridge consists of a paper and plastic device with no moving parts and provides results in less than 30 minutes. This low complexity diagnostic t...