Title：A Gold Nanoparticles and MXene Nanocomposite Based Electrochemical Sensor for Point-of-Care Monitoring of Serum Biomarkers
Journal: ACS Nano
IF: 15.8
Original link：https://pubs.acs.org/doi/full/10.1021/acsnano.5c03194
Reporter：Jiayu Liang-23-master
The development of portable, cost-effective, and highly sensitive biosensors for real-time biomarker detection is crucial for advancing point-of-care testing (POCT) and wearable health monitoring. Here, we present an integrated portable electrochemical sensor (ip-ECS) that combines gold nanoparticles (AuNPs) and MXene-modified screen-printed electrodes (SPEs) with a custom-designed, low-power electronic system for point-of-care monitoring of serum biomarkers. The AuNPs and MXene nanocomposite significantly enhances the electrochemical performance of the SPE by providing a high density of active sites, improved conductivity, and catalytic activity. The detection of two model molecules (DA and UA) validated the feasibility of ip-ECS, achieving detection limits as low as 1.12 and 1.11 μM for UA and DA, respectively. Furthermore, the ip-ECS was successfully applied to detect Cys C in human serum, showing a linear response in the range of 50–5000 ng/mL and a strong correlation (ρ = 0.9556) with conventional latex immunoturbidimetry (LIA). Clinical validation using serum samples from pregnant women revealed elevated Cys C levels in gestational diabetes mellitus (GDM) patients, highlighting the sensor’s potential for early GDM risk prediction. The ip-ECS represents a significant step forward in the development of next-generation biosensors for POCT, wearable diagnostics, and personalized medicine.
The accurate and rapid detection of biomarkers such as uric acid (UA), dopamine (DA), and cystatin C (Cys C) is critical for diagnosing and monitoring a wide range of physiological and pathological conditions. UA, a key metabolite in purine metabolism, is closely associated with hyperuricemia, gout, and cardiovascular diseases, while DA, a vital neurotransmitter, plays a central role in neurological disorders such as Parkinson’s disease and schizophrenia. Similarly, Cys C, a cysteine protease inhibitor, serves as a sensitive biomarker for renal dysfunction and has emerging relevance in predicting complications such as gestational diabetes mellitus (GDM). Conventional methods for detecting these biomarkers, including high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assays (ELISA), and automated biochemical analyzers, often suffer from limitations such as high costs, complex protocols, and reliance on centralized laboratory infrastructure. Consequently, there is a pressing need for portable, cost-effective, and highly sensitive biosensing platforms that enable real-time, point-of-care testing (POCT) and wearable health monitoring.
Electrochemical sensing has emerged as a powerful alternative due to its simplicity, high sensitivity, rapid response, and potential for miniaturization. However, most electrochemical detection methods still rely on traditional desktop electrochemical workstations (dECWs)and three-electrode systems, which cannot be wearable, miniaturized, and used in the home. In recent years, the combination of portable mini-electrochemical workstations (mECWs)and screen-printed electrodes (SPEs) has received a lot of attention due to its advantages of miniaturization and ease of home use. The production of miniaturized, portable electrochemical workstations relies on versatile printed circuit board (PCB) designs. The SPE miniaturizes and flattens the three-electrode system used in traditional desktop electrochemical workstations, making it more suitable for portable mECWs. SPE is also low cost and easy to mass produce with the help of a fully automatic screen-printed machine. Therefore, the combination of small portable electrochemical sensors and SPE will be widely used in the future for highly sensitive and accurate on-site quantification in out-of-hospital scenarios such as home disease management, enabling optimal medical decisions to be made without leaving home.
Recent advances in nanotechnology have further enhanced the performance of electrochemical sensors. The integration of nanomaterials such as gold nanoparticles (AuNPs) and two-dimensional (2D) materials like MXene (Ti3C2Tx) and carbon black have shown remarkable improvements in the sensitivity, selectivity, and stability of sensors. AuNPs are well-known for their excellent electrical conductivity, high surface area, and biocompatibility, making them ideal for electrochemical applications. MXene, a novel class of 2D materials, exhibits outstanding electrical conductivity, mechanical strength, and large specific surface area, providing an excellent platform for electrochemical sensing. While our previous work demonstrated rapid and in situ electrodeposition of MXene/AuNPs composites on SPEs for multiplexed biomarker detection. Some significant gaps remain in developing a fully integrated systems that combine optimized nanocomposite interfaces and a portable electronic readout device. Most existing sensors rely on bulky potentiostats for data acquisition, limiting their practicality for decentralized settings. Furthermore, clinical validation of such systems for complex applications, such as predicting pregnancy-related disorders like GDM, is rarely demonstrated.
Herein, we present a novel integrated portable electrochemical sensor (ip-ECS) that synergizes AuNPs and MXene-modified SPEs with a custom-designed, low-power electronic system for wireless, real-time biomarker detection. The sensor leverages the high conductivity of MXene and the catalytic properties of AuNPs to achieve the ultrasensitive detection of UA, DA, and Cys C. A scalable screen-printing process ensures cost-effective mass production, while the integration of Bluetooth-enabled microelectronics facilitates seamless data transmission to mobile devices. The ip-ECS was rigorously validated against commercial electrochemical workstations and clinical standards, demonstrating excellent sensitivity, selectivity, and stability for the detection of mode molecules (DA and UA). Notably, the sensor was successfully applied to quantify Cys C in serum samples from pregnant women, revealing elevated levels in GDM patients and underscoring its potential for early risk prediction. This work bridges the gap between nanomaterial innovation and practical clinical application, offering a versatile platform for next-generation POCT and wearable diagnostics. Also, these innovations position the ip-ECS as a transformative tool for decentralized healthcare and personalized medicine.
1. Design and Preparation of the ip-ECS
To enhance the electrochemical performance of the SPE, the working electrodes were modified with AuNPs and MXene nanocomposites, forming what was referred to as the AuNPs and MXene-SPE. This modification introduced additional electroactive sites and significantly improved the electrode’s conductivity (Figure 1D). The overall electronic device was designed for compactness and low power consumption, facilitating its use in portable settings (Figure 1E). Overall, this integrated sensor platform combined scalable fabrication, advanced electrode modifications, and compact electronics to achieve high sensitivity, portability, and efficiency for biomarker detection.
2. Fabrication and Characterization of the AuNPs and MXene-SPE
In order to improve the electrochemical performance of SPE, AuNPs and Mxene were modified on its working electrode surface. The structure and morphology of the AuNPs and MXene-SPE were thoroughly characterized using various techniques, including SEM, energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS).
3. Electrochemical Characterization of the AuNPs and MXene-SPE
Optimizing the deposition conditions of AuNPs and MXene is of great significance to improve the overall electrochemical performance of AuNPs and MXene-SPE. To investigate the effect of fabrication conditions on the electrochemical performance of AuNPs and MXene-SPE, typical ferricyanide probes were selected as response analytes. In summary, the optimal deposition conditions for the AuNPs and MXene-SPE were determined as follows: 1 mg/mL MXene was first drop-coated onto the working electrode region of the plasma-treated bare SPE. AuNPs were then deposited onto the MXene surface by CV using an electrolyte of 4 mM HAuCl4 in 0.5 M H2SO4. Electrodeposition was performed at a scan rate of 0.1 V/s over 20 cycles with a potential range of −0.2 to 1.2 V versus Ag/AgCl.
4. Electrochemical Performance of the ip-ECS for the Detection of DA and UA
The electrochemical performance of the ip-ECS was evaluated under optimized experimental conditions by detecting varying concentrations of UA and DA. During detection, DA underwent oxidation to DA-o-quinone, while UA was oxidized to allantoin. These redox reactions were facilitated by the presence of AuNPs and MXene, which synergistically enhanced electron transfer and improved sensor performance.
5. Electronic Design of ip-ECS and Real Sample Analysis
A compact and lightweight system is an essential component for assembling an integrated and portable sensor. To evaluate the detection performance of ip-ECS, we compared the electrochemical workstation with ip-ECS. All the results confirm the reliability of integrated circuits. To evaluate the practical applicability of the ip-ECS, the sensor was tested for the detection of UA in real human serum samples. Additionally, recovery tests were performed for both UA and DA to assess the sensor’s reliability and performance. The ip-ECS was used to detect UA in 36 serum samples, and the results were compared with those obtained from a commercial automatic biochemical system. This demonstrates that the ip-ECS provides reliable and rapid determination of UA in human serum samples.
6. Clinical Application of ip-ECS in Predicting GDM Pregnancies
The feasibility of the ip-ECS was first validated through the detection of two model molecules, DA and UA. To assess the clinical applicability of ip-ECS, we focused on the detection of Cys C, a cysteine protease inhibitor produced by nearly all human cells and excreted into the bloodstream. Cys C has well-established clinical relevance, particularly in evaluating glomerular function, microvascular endothelial injury, and secondary inflammatory responses. Importantly, these pathophysiological processes are also involved in the development of GDM, a condition that is associated with renal impairment. Therefore, the detection of Cys C in serum samples from pregnant women using ip-ECS provides a rapid and noninvasive method to predict the risk of GDM. Therefore, ip-ECS has shown a certain ability to predict GDM in pregnant women and can assist clinicians in making clinical diagnoses and facilitating home testing of pregnant women.
This work introduces a low-cost (USD 0.25/electrode), portable ip-ECS integrating AuNPs/MXene nanocomposites and Bluetooth-enabled electronics. Key achievements include:
1）Multiplexed detection of UA, DA, and CysC with high sensitivity and selectivity.
2）Clinical validation for GDM prediction, demonstrating potential for POCT and personalized medicine.
3）Scalable production via screen printing, addressing cost and accessibility barriers in resource-limited settings.
Future directions involve expanding the sensor’s biomarker panel and integrating AI-driven data analysis for real-time health monitoring.