Joint replacement surgeries of orthopedic implants are progressing at an increased rate in the United States, with around 1 million surgeries being performed annually1. These implants are made of materials such as metals, ceramic, or polyethylene and are biocompatible as well as safe to use 2. While orthopedic implants provide a solution for a damaged joint, metal debris generated due to the wear and corrosion of the implants proves to be of considerable risk of systemic and local toxicity3. CoCrMo implants are widely used metal on metal implants due to their increased resistance to wear compared to the metal on polyethylene implants4. But recent clinical reports suggested that the failure rate of these implants is steadily increasing 5. It was observed that metal ions generated from the wear of CoCrMo alloys diffuse into the surrounding tissues as well as to other locations, thereby leading to implant failure owing to inflammatory immune responses6.
Previously, efforts have been made to detect metal ions released from implants from the serum, urine, and synovial fluid. While the metal-ion content in the blood can be an indicator of osteolysis of bones7, this also helps monitor implant activity in patients with metal-on-metal implants. In 2008, a translational study was conducted on the serum of twenty-six patients with existing metal-on-metal implants who had to undergo revision surgeries, revealing increased metal ion levels in their serum. This suggests a possible correlation between the metal ion content and implant failure8. With the development of technology, inductively coupled plasma mass spectroscopy (ICP-MS) has been adapted to measure the metal ion concentration in solution. Many studies report the quantification of metal ions by ICP-MS from simulated body fluids to study tribocorrosion and corrosion kinetics. Showing that the method is one of the most sensitive and powerful tools to measure metal ion content in biological fluids9. However, this method's requirement of large sample volumes is a major shortcoming. In the previously translational study, around 10 mL of blood was collected from each patient through intravenous catheters due to a minimum requirement of 5 mL needed for ICP-MS analysis8,10. Moreover, other disadvantages of this method include economic unsuitability and unavailability of resources while also requiring trained personnel to operate the machines11. Therefore, there is a need for an economical, accurate and rapid metal ion detection method requiring lesser sample volumes from patients.
Electrochemical tests have been employed to detect heavy metal ions in environmental samples and water to determine the detrimental effects of these metal ions in humans12. These tests can also be used to detect the concentration of heavy metals in serum and other biological fluids by passing a current through a solution and measuring the response signal13. The presence of heavy metal ions in the solution (electrolyte) causes various changes in electrochemical parameters such as impedance, conductivity, current, and voltage. Electrochemical signals can be used to analyze and correlate using existing equivalent circuits to obtain quantitative data14,15
Screen-printed electrodes were first introduced in 1997 and are currently gaining use as a cheap, affordable, and convenient method to study electrochemical reactions13,16,17, 18. They offer multiple advantages over general clinical diagnostic methods, such as miniaturization and easy sample preparation19. Our previous study developed a screen-printed electrode system to examine metal release kinetics in BCS solution. After the estimation of the metal ions by ICP-MS, the dropsens biosensor technique was compared and concluded to estimate metal ions in biological solutions effectively. The study revealed preliminary data that could aid in the establishment of an affordable, patient-friendly point of care (POC) device akin to a glucometer to monitor implant performance20.
In this study, mice models are designed to validate the sensor as a diagnostic tool further. The electrochemical Dropsens biosensor is used to detect electrical impedance and cyclic voltammetry in the mice serum that could directly correlate to the presence and concentration of metal ions. Thereby the results can provide a rapid method of detection for metal ions requiring a small volume of biological serum. This can further be developed into a hand-held device through the technologically developing field of portable potentiostats21,22.