Sensitive and simultaneous detection of multi-index lung cancer biomarkers by an NIR-Ⅱ fluorescence lateral-flow immunoassay platform

Abstract

The simultaneous detection of multiple serum biomarkers of cancer with high sensitivity and point-of-care manner is of great significance for facile and early screening of cancers. In this work, the sensitivity of lateral-flow immunoassay (LFIA) platform was improved by two strategies. The NIR-Ⅱ emitting lead sulfide quantum dots (PbS QDs) were employed to replace common visible region fluorophores to reduce background interference from sample matrix. Meanwhile, numerous hydrophobic PbS QDs were concentrated and assembled within single dendritic scaffold via three-dimensional distribution manner to enhance the fluorescence intensity of individual colloidal label. The LFIA strips with multi-testing lines were performed to realize simultaneous diagnosis of carcino-embryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1) and neuron-specific enolase (NSE). The multi-target LFIA could be completed within 12 min with precise quantitative results by a portable NIR-Ⅱ strip scanner. The analytical data illustrated wide linear detection ranges of 0.11–100 ng mL−1, 0.18–100 ng mL−1 and 0.28–100 ng mL−1 and limit of detection of 0.11, 0.18 and 0.28 ng mL−1 for CEA, Cyfra21-1 and NSE, respectively. The multi-target LFIA revealed minor cross-reactivity of three specific antibodies conjugated labels with non-specific cancer biomarkers and interfering proteins in human serum. For real serums of lung cancer patients and healthy persons, the combination detection of the three biomarkers exhibited an improved sensitivity up to 92.7%, which was significantly higher than any individual biomarker detection, with a satisfactory specificity of 92.0%. The multi-target LFIA platform with high sensitivity and specificity holds great significance for point-of-care and simultaneous diagnosis of multiple cancer biomarkers.