Electrical Detection of C-Reactive Protein Using a Single Free-Standing, Thermally Controlled Piezoresistive Microcantilever for Highly Reproducible and Accurate Measurements

Abstract

This study demonstrates a novel method for electrical detection of C-reactive protein (CRP) as a means of identifying an infection in the body, or as a cardiovascular disease risk assay. The method uses a single free-standing, thermally controlled piezoresistive microcantilever biosensor. In a commonly used sensing arrangement of conventional dual cantilevers in the Wheatstone bridge circuit, reference and gold-coated sensing cantilevers that inherently have heterogeneous surface materials and different multilayer structures may yield independent responses to the liquid environmental changes of chemical substances, flow field and temperature, leading to unwanted signal disturbance for biosensing targets. In this study, the single free-standing microcantilever for biosensing applications is employed to resolve the dual-beam problem of individual responses in chemical solutions and, in a thermally controlled system, to maintain its sensor performance due to the sensitive temperature effect. With this type of single temperature-controlled microcantilever sensor, the electrical detection of various CRP concentrations from 1 μg/mL to 200 μg/mL was performed, which covers the clinically relevant range. Induced surface stresses were measured at between 0.25 N/m and 3.4 N/m with high reproducibility. Moreover, the binding affinity (KD) of CRP and anti-CRP interaction was found to be 18.83 ± 2.99 μg/mL, which agreed with results in previous reported studies. This biosensing technique thus proves valuable in detecting inflammation, and in cardiovascular disease risk assays.

Recent advances in lab-on-a-chip for biosensing applications

“…Antibodies are by far the most commonly employed biorecognition elements as they provide both a strong and specific binding to the target analyte. This yields LODs in the nanomolar range Yen et al, 2013) for proteins, but also routinely in the picomolar range and even, in some cases, into the attomolar range (Yin et al, 2013). Also commonly used are DNA capture probes, allowing, e.g., detection of harmful pathogens, such as HIV in blood at a nanomolar range (Alodhayb et al, 2013), and aptamers for detection of proteins .…”

Sensors and Biosensors for C-Reactive Protein, Temperature and pH, and Their Applications for Monitoring Wound Healing: A Review

“…Yen et al described a SiO 2 /Si 3 N 4 /doped poly-Si/Si 3 N 4 / SiO 2 microcantilever, where silicon nitride was used for passivation and insulation, whereas the oxide to balance the built-in stress ( Figure 4 b) [ 111 ]. This microcantilever had a linear response in the range 10–100 µg/mL (detection time about 50 min).…”

Electrochemical Detection of C-Reactive Protein in Human Serum Based on Self-Assembled Monolayer-Modified Interdigitated Wave-Shaped Electrode

“…Therefore, detection of very low levels of CRP is needed for early detection of cardiovascular risk and inflammatory events. Several methods have been reported for CRP detection, including a CRP enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance [6], piezoelectric cantilevers [7], quartz crystal microbalances [8], and electrochemical analysis [9], as well as nephelometric, turbidimetric, and luminometric methods [10]. However, many efforts are still ongoing to improve the detection limit, dynamic range, reliability, cost, and measurement speed of such analytical methods.…”