BMED 2803 Biostatistics Michael Gadaleta, Amanda Gannon, Joshua Ross, Vikram Sampath

1. Statistical Analysis of Mechanical Characteristics to Validate the Development of a Flexible Electrode BMED 2803 Biostatistics Michael Gadaleta, Amanda Gannon, Joshua Ross, Vikram Sampath Wallace H. Coulter Department of Biomedical Engineering, Laboratory for Neuroengineering, Georgia Institute of Technology Introduction Testing of the Electrodes After traumatic brain injury (TBI) the actual area of the trauma usually sustains a significant mechanical impact. Due to the stresses and strains from TBI there are often times major impairments in the hippocampus; the area of the brain responsible for learning and memory. Because of the limitations in electrical recording technology, not a lot is known about electrical readings inside of the brain. In order to read certain areas of the brain anelectrode needs to be used. In Dr. MichelleLaPlaca’slab, PhD candidate Brock Webster is trying to find such an electrode that can measure the electrical activity of both the cortical and hippocampal areas of the brain in patients with head trauma. In order to do read this electrical activity, he has created a flexible electrode; compared to unreliable rigid electrodes used today. The process of creating and etching each electrode is very detailed and prone to human error. In order to validate the process of developing these electrodes, tests were performed to confirm that the mechanical characteristics for each electrode met not only environmental conditions, but also proposed thresholds for material used. Our group will use some statistical methods that will aid in this confirmation. When designing a flexible electrode there are many mechanical variables that must be met and analyzed before any type of clinical trial can be performed. Using statistical analysis, our group was able to assess several of the major mechanical characteristics including yield stress, elastic modulus, and hardness of the device, using data given from Brock Wester’s lab. Each electrode is designed to be implanted into the brain. During this process, the electrode is inserted into the brain perpendicularly using micro tweezers. Initially, the electrode must be strong enough to pierce the dura and brain tissues. The force needed to pierce these tissues must be greater than 1 mN. Therefore, the yield stress or buckling force must be higher than the maximum force needed to pierce the tissue. To test this threshold, 9 individual electrodes were subjected to a force to determine the buckling threshold. Elastic modulus and Hardness describes the parylene coating which makes up every electrode. In order to prove that the parylene coating has the same flexibility throughout, an indentation test was performed where engineering stress and strain were measured and using these values, elastic modulus and hardness was calculated. The significance of these tests is to prove that every electrode is the same and that they can withstand environmental conditions. Thus, proving that the method used to make the new flexible electrode is repeatable and reproducible. Making of the Electrodes Results The first statistical analysis was to justify that the values of the yield stress (buckling force) of each individual electrode is the same, a one variable T-test was performed. In order to continue testing with each electrode, the mean pressure must be greater than the predicted tissue pressure of 1 mN, and the percentage of the Coefficient of Variance (CV) must be low. A CV of less than one proves that the dispersion between data points is small. The fact that the CV is low and the mean is above 1, proves that one factor in the process of making the electrodes is repeatable and that each electrode will be able to withstand tissue pressure when it is inserted into the brain. The second analysis was to prove that material used to make the electrode does in fact relate to standard and accepted values. The parylene coating surrounding the electrode was tested based on the parameters of elastic modulus, which encompasses stress and strain, and hardness. Using a one variable T-test for both of these parameters tested, and comparing the average values of each test to the standard book value found, it was found that the p-value for both elastic modulus and hardness was above 5%. This means that the book value is within the standard deviation of the tested values. The hypothesis that mu is equal to 4.15 for elastic modulus and 0.18 for hardness can be accepted. The third and final analysis was done to show a relationship between elastic modulus and hardness of the parylene material. Using regression, our group wanted to show that there is a way to predict elastic modulus if a value for hardness is given, or vice-versa. Running this analysis showed that these two parameters has in fact some correlation between them. Looking at the variable R-Sq, shows that 84% of the data given falls within the regression line and that the two parameters are related. Statistical Methods Conclusions Throughout our project, statistical procedures were carried out in order to validate the process of development of the flexible electrode. With the help of acceptable standards and known environmental conditions, we were able to test the experimental data against these known values. As can be seen from the statistical data, all values for mechanical testing of the electrode fall within the acceptable regions of their corresponding tests, thus proving that manufacturing each flexible electrode is repeatable. • Steps of Etching Process • Parylene is deposited on the substrate. • A photoresistant layer is spun on the surface • Using a chrome mask, uv light hits the ends of the surface • Photoresist development occurs. • Gold is deposited to make conduction lines. • Photoresistant and gold layers are removed and lifted off from ends. • Parylene is deposited evenly. • Photoresistant is added and exposed to uv light using chrome masks. • Photoresistant is developed. • Aluminum protective layer is added. • Aluminum and the photoresistant layers are removed from ends. • Process of REI etching is used to remove the parylene outside layers while the aluminum in the core helps protect the remaining parylene from bombardment. • Aluminum is wet etched off the surface. • The parylene and gold electrode is removed from the substrate. References 1. Lee, Cho, Hyungsuk, Junghyn. "Development of Conformal PDMS and Parylene Coatings for Microelectronics and MEMS Packaging." ASME International Mechanical Engineering Congress and Exposition (2001): 1-5. 2. Wester, Brock. Department of Neuroengineering. Ph. D Candidate. “Acquisition and assessment of localized electrical activity of the brain in the acute period following trauma”. PowerPoint. Acknowledgements We would like to thank Brock Wester for the data and guidance in the understanding of his research as well as Brani Vidakovic for his statistical expertise.