Metal Ion Burst Release Characterization and Accelerated Testing Methods on Nitinol
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Contributing OfficeCenter for Devices and Radiological Health
Abstract
Nitinol, an alloy of 50% nickel (Ni) and 50% titanium, has unique mechanical properties which are essential for the function of devices including cardiovascular stents or orthopedic wires. Despite the mechanical properties gained by using nitinol, Ni release from these devices can occur, and Ni is associated with a range of toxicological effects such as systemic toxicity and allergic reaction in individuals who have Ni sensitivity. Thus, accurate Ni release testing of nitinol devices is integral to evaluating this potential toxicological risk. However, the extent to which current benchtop methods for measuring metal ion release (e.g., ASTM F3306-19) replicate corrosion observed on implanted medical devices is unknown. A test method amenable to collecting metal ion release data under many different media conditions in parallel would aid in evaluating various in vivo simulating conditions simultaneously. The ASTM F3306-19 method quantifies ion release over a three-month period and samples are taken at predetermined time points to characterize ion release. This method is labor intensive and can be optimized to save time and resources. Additionally, samples are taken once daily for the first week, but this approach does not capture the burst release phase, which occurs primarily within the first few hours or day. The goals of this study are to develop a test method that can be used to investigate the burst release of Ni and can facilitate experiments in parallel with minimal human mediation to reduce variability in the data. A microfluidic flow system was built to continuously monitor Ni ion release from test samples over 8-hour periods. A 155 µL/min flow rate of phosphate-buffered saline (PBS) is pumped over a nitinol plate with a 13.2 cm2 exposed surface area. The leachate is continuously analyzed using an on-line inductively coupled mass spectrometry (ICP-MS) and quantification of the Ni release is calibrated using regular injections of known Ni mass. Concurrently, fractions are collected at predetermined time intervals for off-line ICP-MS analysis to verify the accuracy of the on-line analysis. The test is repeated at multiple temperatures between 37 C and 80 C to determine whether Ni ion release follows Arrhenius kinetics, which can allow for developing and justifying accelerated testing approaches. Additionally, these studies are performed using nitinol plates with different surface finishes that represent a range of finishes that may be found on medical devices (mechanical polish, electropolish, various thermal oxide thicknesses). Qualification of this experimental approach as an accurate and precise method to measure metal ion burst release will allow for study of various method parameters (test fluid formulation, extraction ratio, sampling interval, etc.) in parallel with minimal human intervention. This could lead to reduction in intra- and inter-laboratory accuracy and improved reproducibility. Considering the substantial number of parameters to be tested, this experimental approach could also be used to establish the correlation of in vitro to in vivo test results. Furthermore, the output of this study could be used to advise ASTM F3306 test method development and to support accelerated (high temperature) testing approaches that are intended to reduce the time needed to complete testing.