Disposable Saliva Sensors for Early Cancer Diagnosis Using Hyper-Cross-Linked Molecularly Imprinted Polymeric Electrocatalysts

The quest for accessible, noninvasive cancer diagnostics is largely futile due to numerous practical challenges. In this pursuit, we present a proof-of-concept for developing an affordable cancer diagnosis and prognosis tool using salivary polyamine concentrations as cancer indicators. The cellular production of polyamines, especially spermine, is essentially escalated in cancerous tissues, and its impact is measurable in saliva and other physiological fluids. Herein, highly accessible, inexpensive, and disposable yet operationally stable microelectrodes are designed for the selective electrocatalytic detection of polyamines in human saliva. These electrodes are modified with a spermine-imprinted hyper-cross-linked copolymer: poly(methacrylic acid-co-2,4,6-triallyloxy-1,3,5-triazine), with g-C3N4 nanosheets embedded into it (sPMA2TA@g-C3N4), for enhanced sensitivity and target specificity. This biomimetic electrocatalytic layer shows remarkable spermine identification and quantification capability, with 0.82 μA cm–2 nM–1 sensitivity, a 37.5 pM limit of detection, and an 114.1 pM limit of quantification. The reported device exhibits extraordinary selectivity over multiple salivary analytes with pendant amino groups. The real-world utility of the sPMA2TA@g-C3N4 sensor is demonstrated by rapid and accurate quantification of spermine, with 97.4 ± 2.3% (n = 3) recovery of spiked spermine concentrations in saliva droplets, and excellent stability after several cycles of measurements spanning over 2 weeks. The development and validation of this sensor offer accessible and timely cancer diagnosis and prognosis, potentially revolutionizing the healthcare landscape.