Smartphone-connected, battery-free aptamer-based digital test for quantification of procalcitonin and monitoring of infection at the point of care

Abstract

Background: Rapid and accurate measurement of procalcitonin (PCT) is useful for diagnosing bacterial infections and guiding antibiotic therapy, yet current laboratory-based immunoassays require centralised infrastructure, delaying clinical decision-making and limiting access in low-resource settings. We developed a battery-free, smartphone-connected electrochemical lateral flow assay with linked analytics for the detection of PCT (ELLA-PCT) enabling quantitative testing at the point of care without conventional laboratory instrumentation. Methods: We designed a competitive electrochemical lateral flow assay using gold nanoparticles co-functionalised with a PCT-specific DNA aptamer and ferrocene hexanethiol as a redox reporter. A miniaturised near-field communication (NFC) potentiostat embedded within a disposable cassette enabled wireless electroanalytical measurements using a smartphone. Analytical performance was assessed in buffer and serum, including limit of detection (LOD), linearity, specificity, and stability. Clinical evaluation was performed on 27 serum samples from nine adults undergoing antibiotic treatment for suspected bacterial infection, with results compared against the reference Time-Resolved Amplified Cryptate Emission (TRACE) assay. Findings: ELLA-PCT achieved an LOD of 46 pg/mL and a linear detection range of 0.5-100 ng/mL. The ELLA-PCT assays remained stable for three months under ambient storage conditions, and cross-reactivity with calcitonin, C-reactive protein, and interleukin-6 remained below clinically relevant thresholds. Clinical results showed strong correlation with TRACE (R2 = 0.979, p < 0.0001), with a mean bias of 0.05 ng/mL and narrow 95% limits of agreement (-0.69 to 0.89 ng/mL). Importantly, ELLA-PCT delivered results in only 30 minutes without requiring external power or clinical laboratory instrumentation. In comparison to TRACE, the total turnaround time was reduced by at least 50%, which typically requires at least one hour from sample collection to results at a hospital setting. Interpretation: ELLA-PCT is an antibody-free, smartphone-connected test that provides laboratory-grade quantitative PCT measurement using only an NFC-enabled electroanalytical sensor and a mobile phone. The platform has a strong potential to decentralise diagnosis of infectious diseases, support antibiotic stewardship, and enable remote, real-time monitoring in outpatient and resource-limited settings. Larger studies are needed to evaluate the use of whole-blood samples and the integration of the platform into digital clinical workflows.