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：10.1021/acsnano.5c03194

Reporter：Guannan Dong- M.S. Class of 2023

     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.

    Accurate and rapid detection of biomarkers such as uric acid, dopamine and cystatin C is essential for the diagnosis and monitoring of a variety of physiological and pathological conditions. Traditional detection methods have limitations such as high cost, complex operation, and reliance on centralized laboratory facilities. Electrochemical sensing has the advantages of simplicity, sensitivity, fast response and miniaturization. However, most methods rely on traditional desktop electrochemical workstations, which cannot be wearable and used at home. In recent years, the combination of portable micro-electrochemical workstations and screen-printed electrodes has attracted much attention, and the development of nanotechnology has further improved the performance of electrochemical sensors. However, there are still gaps in the development of integrated systems combining optimized nanocomposite interfaces and portable electronic readout devices, and clinical validation is also scarce, hence the conduct of this study.

Design and Preparation of the ip-ECS.

Figure 1. Illustrations of the ip-ECS. (A) Schematic breakdown of the structure of AuNPs and MXene-SPE, consisting of a PET film substrate, conductive ink layer, Ag/AgCl ink layer, and UV protection layer. (B) Photograph of the fabricated AuNPs and MXene-SPE produced in large quantities using an automated screen-printing machine. (C) Photograph of a single AuNPs and MXene-SPE demonstrating its compactness and flexibility, along with a bending test showcasing its suitability for portable, wearable, and POCT applications. (D) Illustration of the modification process for the working electrodes. MXene is first deposited to provide sites for AuNP growth, followed by electrodeposition of AuNPs to enhance conductivity and introduce additional electroactive sites. (E) Overview of the custom electronic device designed for compact, low-power operation, integrated with the modified AuNPs and MXene-SPE to enable high-performance electrochemical sensing.

Fabrication and Characterization of the AuNPs and MXene-SPE.

Figure 2. Characterization of the AuNPs and MXene-SPE. SEM images showing the morphology of the AuNPs and MXene nanocomposite: (A) The fabrication process of AuNPs and MXene-SPE and morphological characterization under varying conditions. (B−C) MXene with a multilayered accordion-like structure after AuNP deposition. (D) Bare SPE for comparison. (E) Corresponding element mapping images of AuNPs and MXene. (F) EDS spectrum illustrating the uniform distribution of C, Ti, and Au within the composite. (G) TEM image depicting the sheet structure of MXene (about 500−600 nm) and AuNP sizes ranging from 6 to 24 nm according to the histogram of AuNPs sizes.

Electrochemical Characterization of the AuNPs and MXene-SPE

Figure 3. XRD and XPS spectrum ofMXene and AuNPs and MXene samples. (A) XRD spectrum ofMXene and AuNPs and MXene samples. (B) XPS full profile ofMXene and AuNPs and MXene samples. High resolution XPS spectra of(C) C 1s for AuNPs and MXene, (D) O 1s for AuNPs and MXene, (E) Ti 2p for AuNPs and MXene, (F)Au 4f for AuNPs and MXene.

Electrochemical Performance of the ip-ECS for the Detection of DA and UA.

Figure 4. Electrochemical Characterization of the AuNPs and MXene-SPE. (A) CV, EIS, and DPV methods were used to select the best modification conditions for AuNPs and MXene-SPE. The metrics used to evaluate optimization were ΔEp, Rct, and Ip. CV curves of AuNPs and MXene-SPE under varying conditions, including different MXene concentrations (B), scan rates (C), and CV deposition segments (D). EIS curves of AuNPs and MXene-SPE under varying conditions, including different MXene concentrations (E), scan rates (F), and CV deposition segments (G).

Electronic Design of ip-ECS and Real Sample Analysis.

Figure 6. Performance characterization of ip-ECS and Real sample analysis. (A) The system block diagram of PCB. (B) The photograph of PCB. (C) Comparison of DPV curves of 200 and 1000 μM UA detected by ip-ECS and CHI650, respectively. (D) Comparison of Ip of 200 and 1000 μM UA detected by ip-ECS and CHI650, respectively. (E) Detection process for the automatic biochemical system and the proposed ip-ECS. (F) Comparison ofUA measurements in 36 serum samples detected by the automatic biochemical system and the ip-ECS. (G) Comparison ofUA concentrations measured by the automatic biochemical system (y-axis) and the ip-ECS (x-axis). The correlation was determined based on the Pearson product-moment correlation coefficient (ρ = 0.995), demonstrating a high degree of agreement between the routine automatic biochemical system and the proposed sensor.

Clinical Application of ip-ECS in Predicting GDM Pregnancies.

Figure 7. Application of ip-ECS for detecting serum Cys C in pregnant women. (A) The process of predicting the risk of GDM in pregnant women based on serum Cys C level (i), and working principle for the electrochemical detection for Cys C (ii). (B) Electrochemical responses for detecting different concentrations ofCys C (From the back to the front: 50, 100, 200, 500, 700, 1000, 2500, and 5000 ng/mL). (C) The calibration curve for Cys C ranges from 50 to 5000 ng/mL. (D) Selectivity of the ip-ECS for detecting Cys C and common serum protein interferents. (E) Stability of the current response for Cys C over a 30-day storage period. (F) Comparison of Cys C concentrations measured by LIA (x-axis) and the ip-ECS (y-axis). The correlation was determined based on the Pearson product-moment correlation coefficient (ρ = 0.9556). (G) Comparison of Cys C concentrations in healthy pregnancies and GDM pregnancies, detected by the automatic biochemical system and the ip-ECS.

Research Conclusion

The developed ip-ECS can sensitively and rapidly detect UA, DA and Cys C in serum with high sensitivity, selectivity and stability. The detection results are well correlated with traditional methods, and can reliably determine biomarkers. It has the application potential in predicting the risk of GDM, which is an important progress in the next generation of diagnostic tools.