Miniaturized Electrochemical System for Rapid and Real-time Detection of Blood Biomarkers

Abstract

Blood contains a wealth of biomarkers that can provide insights into an individual’s health status, evaluate physiological functions, and facilitate disease diagnosis. Consequently, the precise detection of biomarker molecules in blood has emerged as a crucial clinical tool for disease screening and diagnosis. However, traditional clinical biochemical analyses are often dependent on large, costly instruments that require operation by trained personnel. Furthermore, most existing equipment lacks the capability for rapid, real-time, and continuous monitoring, thereby restricting its application in emergency care and routine health assessments. Additionally, the necessity for frequent hospital visits can lead to patient inconvenience and discomfort due to invasive sampling methods, such as blood drawing. These limitations significantly impede the effectiveness and applicability of conventional diagnostic devices in the realms of disease diagnosis, treatment, and prognosis. There is a pressing need for the development of rapid, real-time, and in situ point-of-care testing (POCT) blood marker sensors. The foundation of home-based, rapid blood testing lies in the integration of portable devices, minimally invasive sampling techniques, and wireless data transmission. In this study, we present the development of a portable health monitoring system capable of rapid detection of blood cancer biomarkers, in situ blood sampling, and real-time detection of blood cardiac troponin using microneedles, thereby alleviating the need for patients to travel to healthcare facilities for blood testing.

To facilitate the rapid detection of biomarkers in blood, we have developed an innovative label-free immunosensor utilizing multiwall carbon nanotubes (MWCNTs) and thionine (Thi). This system employs an electrochemical detection method to achieve swift identification of tumor markers, specifically alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), in blood samples. We have modified nanomaterial MWCNTs to serve as a substrate of the detection electrode, which increases the loading capacity for thionine and antibodies, while demonstrating exceptional catalytic performance and signal amplification for current detection in various electrochemical processes. The incorporation of MWCNTs and Thi into electrochemical biosensors markedly enhances the electrochemical activity of target analytes in comparison to conventional bare electrodes, thereby enabling sensitive and rapid quantitative analysis of biomarkers. In comparison to the traditional enzyme-linked immunosorbent assay (ELISA), the sensor allows for the rapid detection of AFP and CEA, achieving low detection limits for AFP and CEA. Furthermore, the sensor exhibits commendable high sensitivity, selectivity, recovery, and ease of operation, with the potential for parallel high-throughput analysis. The simplicity and portability of this nanomaterial-based sensor technology positions it as a versatile platform for the development of other biosensors, representing a significant technological advancement in the realm of biomarker detection and POCT.

In response to the limitations associated with conventional blood sampling techniques, we have developed a minimally invasive and painless biosensing system that employs a microneedle architecture. This innovative platform integrates both sampling and detection capabilities, facilitating rapid, and real-time identification of biomarkers present in minute volumes of blood. The system utilizes microneedles to penetrate the stratum corneum of the skin for fingertip blood sampling, coupled with electrochemical analysis to directly measure the concentrations of blood biomarkers. Notably, this microneedle immune electrode obviates the need for extraction or external analysis, thereby mitigating issues related to sampling procedures, time delays, and contamination. However, it is important to note that microneedles possess a limited surface area compared to patches, which significantly diminishes detection sensitivity. To address this challenge, we enhanced the microneedle surface by applying a composite material composed of chitosan, multi-walled carbon nanotubes, and thionine (CS/MWCNTs/Thi), thereby increasing the specific surface area of the sensitive membrane and markedly improving sensitivity.

In our validation experiments, we focused on the transdermal extraction and sensitive detection of blood troponins (cTnT and cTnI), which are critical biomarkers in the pathogenesis of myocardial infarction (MI) and serve as significant indicators of cardiovascular disease. The microneedle-based electrochemical immunosensor demonstrated rapid and effective detection of cTnT and cTnI in buffer solutions, with detectable concentration ranges spanning from 100 fg/mL to 1 μg/mL with low detection limits. Furthermore, the immunosensor exhibited commendable reproducibility, high sensitivity, and stability under optimal conditions. This blood detection method allows rapid and reliable identification of cTnT and cTnI in blood samples, demonstrating high selectivity for the target biomarkers even in the presence of potential interfering substances. Utilizing this compact, portable, and wearable microneedle sensor as a platform, we can incorporate power supply and data transmission capabilities, enabling Bluetooth low energy (BLE) to a graphical user interface via a wireless communication technology framework. The integration aims to facilitate the rapid detection of health conditions and diseases within a home setting.

In conclusion, we developed a series of miniaturized and portable sensor systems for blood biomarker detection. Our research has involved comprehensive parameter optimization to mitigate the challenges associated with traditional, complex, and time-intensive sampling methods, as well as to enhance the sensitivity of marker detection. We can significantly reduce the dependence on centralized hospitals and large-scale equipment by implementing minimally invasive and rapid monitoring techniques. The microneedle sensors present an optimal solution for rapid at-home testing, particularly for chronic conditions such as oncology and acute situations like myocardial infarction, which necessitate frequent or rapid monitoring, as well as for the management of personalized medication regimens, such as in diabetes care.

Date of Award	16 Sept 2025
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Xinge YU (Supervisor)