Electrochemical Biosensor to Detect Implant Derived Metal Ions: A Mice Model

Abstract

Joint replacement surgeries are progressing at an increased rate in the United States, with around 1 million surgeries being performed annually. While these orthopedic implants provide a solution for a damaged joint, debris such as metal ions generated due to the wear and corrosion of the implants prove to be of considerable risk of systemic and local toxicity. As an effective diagnostic tool, there is a need to develop a patient-friendly, cost-effective, and rapid mode of metal ion detection in orthopedic patients with various implants. In this study, an electrochemical biosensor chip (Dropsens) is proposed as a diagnostic tool to detect metal ions through changes in impedance. In vivo studies were conducted using CoCrMo particles intra-particularly injected into mice. Then, blood was collected on 0th day, 14th day, and 28th day after injection and was centrifuged to obtain serum. The serum was subject to various electrochemical techniques such as Electrochemical Impedance Spectroscopy (EIS) and cyclic voltammetry (CV). Additionally, standardization experiments were performed using different concentrations of CoCrMo wear particles suspended in PBS and mice serum. The EIS standardization experiments reveal a negative correlation between impedance (Rp) value obtained after fitting with the equivalent CPE model and metal ion concentration in mice serum. A regression equation was obtained from the standard experiments. The CV data for differing metal ion concentrations and the regression equation were also obtained. The mice model data, the bode plot which depicts the change in impedance and phase angle at each frequency, the positive control group shows the highest impedance at any frequency followed by the experimental 28th day mice serum. The % change in impedance between the different groups revealed the increasing presence of metal ions in serum on 28th day. The CV experimental data obtained reveal a possible correlation between CV area and metal ion concentrations. Experimental mice models were established to mimic the possible diffusion of metal particles from implants. Dropsens electrochemical biosensors were efficiently employed to detect metal ions in serum through changes in impedance.