Proximity Amplification-Enabled Electrochemical Analysis of Tumor-Associated Glycoprotein Biomarkers

Abstract

Glycoproteins produced and secreted from specific cells and tissues are associated with several diseases and emerge as typical biomarkers to provide useful information in cancer diagnosis considering their abnormal expression levels. In this work, we design a universal method to achieve the accurate and sensitive analysis of tumor-associated glycoprotein biomarkers based on both carbohydrate recognition and protein recognition at the same protein surface. The byproduct of dual recognition-induced proximity amplification, pyrophosphate, triggers the disassembly of methylene blue-encapsulated metal−organic frameworks, MB@ZIF-90. As a result, methylene blue molecules are released to arouse amplified electrochemical responses for glycoprotein analysis. Experimental results demonstrate the high-accuracy analysis of carcinoembryonic antigen, a typical glycoprotein biomarker in cancer diagnosis, in a linear range of 0.001−100 ng mL −1 with a low limit of detection of 0.419 pg mL −1 . The method also displays satisfactory specificity and recoveries in complex serum samples and proves good versatility by adopting two other tumor-associated glycoprotein biomarkers, α-fetoprotein and mucin-1, as the targets. Therefore, this work provides a valuable tool for the analysis of glycoprotein biomarkers, which may be of great potential in early warning of malignant tumors in clinical applications.

Functional Interface for Glycoprotein Sensing: Focusing on Biosensors

“…For another example, a proximity amplification strategy for electrochemical determination of CEA was recently reported, with a low limit of detection of 0.419 pg/mL and a wide linear range from 0.001 to 100 ng/mL achieved . In their design, two DNA probes were utilized to enable the simultaneous recognition and labeling of the same CEA glycoprotein molecule through protein and glycan, respectively: one relied on protein recognition via aptamer binding, while the other took advantage of covalent formation with the diols in glycan structures.…”