Rapid Point-of-Care Electrochemical Sensor for the Detection of Cancer Tn Antigen Carbohydrate in Whole Unprocessed Blood

Abstract

Improving outcomes for cancer patients during treatment and monitoring for cancer recurrence requires personalized care which can only be achieved through regular surveillance for biomarkers. Unfortunately, routine detection for blood-based biomarkers is cost-prohibitive using currently specialized laboratories. Using a rapid self-assembly sensing interface amenable to methods of mass production, we demonstrate the ability to detect and quantify a small carbohydrate-based cancer biomarker, Tn antigen (αGalNAc-Ser/Thr) in a small volume of blood, using a test format strip reminiscent of a blood glucose test. The detection of Tn antigen at picomolar levels is achieved through a new transduction mechanism based on the impact of Tn antigen interactions on the molecular dynamic motion of a lectin cross-linked lubricin antifouling brush. In tests performed on retrospective blood plasma samples from patients presenting three different tumor types, differentiation between healthy and diseased patients was achieved, highlighting the clinical potential for cancer monitoring.

Applications of Graphene in Five Senses, Nervous System, and Artificial Muscles

“…Recently, the hospital-on-chip concept has emerged from the fusion of intelligent biosensors, Internet of Medical Things, and fifth generation mobile communication. The blood glucose test has inspired the recognition of carbohydrate as cancer biomarkers for the low cost evaluation of cancer recurrence . The photonic biosensors may promote the handling of complex biological samples. , Field-effect transistors feature the specific and sensitive detection of cancer biomarkers .…”

“…The blood glucose test has inspired the recognition of carbohydrate as cancer biomarkers for the low cost evaluation of cancer recurrence. 280 The photonic biosensors may promote the handling of complex biological samples. 281,282 Field-effect transistors feature the specific and sensitive detection of cancer biomarkers.…”

Reagentless protein-based electrochemical biosensors

“…The end-domains of LUB are very adhesive, and therefore it provides LUB with the capability to self-assemble on different surfaces. 34 When self-assembled onto a surface, LUB adopts a telechelic brush configuration. This brush configuration displays two main characteristics that are very attractive for electrochemical sensing applications.…”

“…45 Second, the LUB brush presents a very diffuse nature (>95% water), creating hence a flexible brush, which is required for electrochemical sensors that are based on the principle of electronic transfer between surface tethered redox reporters and the electrode surface. 34,45 Fig. 3 Therefore in this reagentless protein-based sensing architecture, LUB present multi-functionalities: it anchors the methylene blue-PNA to the electrode surface (referred to as LUB-PNA interface), it works as an antifouling agent, and it also creates a dynamic harmonic motion which is central to the sensing transduction mechanism.…”

“…3 Therefore in this reagentless protein-based sensing architecture, LUB present multi-functionalities: it anchors the methylene blue-PNA to the electrode surface (referred to as LUB-PNA interface), it works as an antifouling agent, and it also creates a dynamic harmonic motion which is central to the sensing transduction mechanism. 34 Fig. 4 shows the LUB-PNA sensing mechanism, where in the absence of the Tn antigen target, the LUB brush is cross-linked with the PNA.…”