A smartphone-connected point-of-care photochemical biosensor for the determination of whole blood creatinine by differential optical signal readout

Abstract

The level of creatinine in the human body has clinical implications with regard to a potential association with kidney, muscle, and thyroid dysfunction, hence necessitating fast and accurate detection, especially at the point-of-care (POC) level. This paper presents the design, fabrication, and feasibility of a compact, low-cost and reliable POC photochemical biosensor connected to a smartphone for the determination of whole blood creatinine by differential optical signal readout. Disposable, dual-channel paper-based test strips were fabricated using stackable multilayer films pre-immobilized with enzymes and reagents for the identification and conversion of creatinine and creatine, resulting in dramatic colorimetric signals. A handheld optical reader was integrated with dual-channel differential optical readout to address endogenous interferences in the enzymatic assay of creatinine. We demonstrated this differential concept with spiked blood samples, obtaining a wide detection range of 20–1483 μmol/L and a low detection limit of 0.03 μmol/L. Further interference experiments displayed the differential measuring system's excellent performance against endogenous interference. Furthermore, the sensor's high reliability was confirmed through comparison with the laboratory method, with the results of 43 clinical tests consistent with the bulky automatic biochemical analyzer, with its correlation coefficient R2 = 0.9782. Additionally, the designed optical reader is Bluetooth-enabled and can connect to a cloud-based smartphone to transmit test data, enabling active health management or remote monitoring. We believe the biosensor has the potential to be an alternative to the current creatinine analysis conducted in hospitals and clinical laboratories, and it has promising prospects for contributing to the development of POC devices.