A novel implantable dual microelectrode for monitoring/predicting post traumatic brain injury seizures
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GROUP 6B Vidhi Chandra, Mi Thant Mon Soe, Dharma Varapula, Chao Wang, Rachel Wang, Tony Yu
IMPLANTABLE DUAL ELECTRODE FOR MONITORING/PREDICTING POST TRAUMATIC BRAIN INJURY SEIZURES
http://www.constantinereport.com/47364/
Overview
● Background ● Description of the problem ● Analysis of currently available treatments ● Design Challenges ● Description/justification of proposed design ● Characterization ● Improvement over existing technologies ● Regulatory pathway ● Incorporation of human factors
Background: Traumatic Brain Injury ● Traumatic Brain Injury1
○ caused by a blow or a penetrating injury that disrupts normal function of brain (falls, accidents) ! Mild: brief change in mental status or
consciousness ! Severe: extended period of unconsciousness
or amnesia after injury • Prevalence
o 1.7 million cases annually2
o 30% of all deaths related to TBI2
o $76.5 billion in 20003 ! 90% related to severe TBI
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Description of the Problem
● Post traumatic seizure ○ seizure resulting from severe TBI that contribute to
secondary damage in brain, may lead to disability4 ■ 16.3% early (1 week after TBI) ■ 25.3% late (typically within a month, few later)
● Problem ○ give anti-seizure medication immediately after TBI5
■ only effective for early PTS (within 1 week)6
○ long term use of anti-seizure medication may increase risk of seizures7
How do we effectively prevent late post traumatic seizures with anti-seizure medication?
Analysis of Currently Available Technologies8
Technology Description Limitation
fMRI Imaging change in blood flow Patients need to keep still; high cost
PET Measurement of emitted energy
from positrons collide with electrons
Higher cost;lower spatial resolution;radioactive
isotopes
Stroke Research Temporarily stop mice from breathing, measure brain O2
Research tool, can’t be used clinically
Jugular Venous Oximetry
Measurement of jugular venous oxygen saturation with fiberoptic
catheter
Poor correlation; extracerebral contamination
Polymer Oxygen Sensor
currently used for in vivo animal studies; electrocatalytic reduction
of oxygen at electrode surface
Large dimensions: 3 cm length
Proposed Design
Implantable dual electrode in the brain post traumatic brain injury (TBI) to measure: • Electrical activity • Brain tissue oxygen
to detect oncoming seizures in order to take anti-seizure medication
Design Challenges • Minimize immune response
• Integrate both electrical and oxygen sensors
• Preserve electrode-tissue interaction after surface modification
• Improve SNR, signal stability and increase residence time needs to be improved
Design: Dual Electrode 10 • Silicon electrode coated with Conductive Polymer,
PEDOT (poly-3,4-ethylene dioxythiophene)- electrodeposition
• 4 sensing elements on each Si microwire- 2 each for O2 & electrical activity sensing
• SnO2 nanowire detects O2 molecules • Dopants introduced to increase cell adhesion,
electroactivity o Biological dopant: DCDPGYIGSR o Synthetic laminin peptide with amino acid sequence:
Asp-Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg
Rationale: Si, SnO2
• Silicon electrode- with PEDOT coating o Ease of fabrication o Both Si & PEDOT are semiconductors o Array- Allows for simultaneous measurements
• Tin oxide (SnO2) o Conductance changes with exposure to oxygen o Non-cytotoxic o Nanowire - lower surface area reduces foreign body
response
Rationale: PEDOT
• Rough surface => more bioactive area => higher charge density
• Provides for cell attachment through choice of dopants => Improved SNR
• Chronic stability of signal, and reduced inflammatory response
Structure of PEDOT10
Neurite outgrowth on laminin doped polymers at 96hr post-plating with bare polymer (left) and laminin coated (right)8
Schematic of conducting polymer electrode array with cell attachment bioactivity8
Characterization • Scanning electron microscopy (SEM): surface
characteristics
• Cyclic voltammetry (CV): total amount of charge transferred
• Cell growth inhibition: toxicity of free dopant ions
• Neural cell differentiation assays: determine neural cell response to PEDOT
• Animal model: overall immune response to design
Improvements Over Existing Technologies
• Simultaneous direct measurement of brain tissue oxygen and electrical activity
• Microarray: simultaneous measurements
• Wireless communicator: online remote monitoring, increases patient mobility
• Early treatment of post-traumatic seizures
Ways to Prevent Oncoming Seizures9
www.bedfordlabs.com/content/dam/internet/opu/bedfordlabs/com_EN/images/products/midazolam/MID%20combo%20lg.jpg
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images/valium.gif
Diazepam- Nasal Spray
Midazolam - injections (like Epipen)
Ativan or Klonpin tablets -Sublingual
● Normal pO2 range: 250- 486 mm Hg ● Normal electrical activity: 80 - 160 Hz
Regulatory Pathway
● Class III device
● Premarket approval (PMA) application
● Non-clinical Laboratory Studies’ Section ○ in vitro tests ○ in vivo animal models
● Clinical Investigations’ Section www.publichealthwatchdog.com
ASTM/ISO Standards • ASTM F2901- 13: Detect neurotoxicity caused by medical
devices that contact nervous tissue
• ISO 10993-4:2002: tests for medical device interactions with blood
• ISO 10993-13:2010: Identification and quantification of degradation products from polymeric medical devices
Human Factors
● Patient Compliance
● Surgery and Surgeon skill ○ take an antibacterial shower! :)
● Reduced need for anchoring - easy probe removal
● Short term effect of electrode insertion www.123rf.com
References [1] Centers for Disease Control and Prevention (CDC), National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Atlanta (GA): Centers for Disease Control and Prevention; 2003. [2] Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010 [3] Finkelstein E, Corso P, Miller T and associates. The Incidence and Economic Burden of Injuries in the United States. New York (NY): Oxford University Press; 2006. [4] Asikainen I, Kaste M, Sarna S. Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia. 1999;40:584–589. [5] Garga, N. and Lowenstein, D. H. (2006), Posttraumatic Epilepsy: A Major Problem in Desperate Need of Major Advances. Epilepsy Currents, 6: 1–5. doi: 10.1111/j.1535-7511.2005.00083.x [6] Teasell, R., Bayona, N., Lippert, C., Villamere, J., & Hellings, C. (2007). Post-traumatic seizure disorder following acquired brain injury. Brain injury, 21(2), 201-214. [7] Tucker GJ (2005). "16: Seizures". In Silver JM, McAllister TW, Yudofsky SC. Textbook Of Traumatic Brain Injury. American Psychiatric Pub., Inc. pp. 309–321. [8] Green et al, “Conducting polymer-hydrogels for medical electrode applications”,Sci. Technol. Adv. Mater. , Vol. 11, 2010 [9] Bragin, A., Wilson, C. L., Staba, R. J., Reddick, M., Fried, I., & Engel, J. (2002). Interictal high-frequency oscillations (80–500Hz) in the human epileptic brain: Entorhinal cortex. Annals of Neurology, 52(4), 407–415. doi:10.1002/ana.10291 [10] Rylie A. Green, Nigel H. Lovell, Gordon G. Wallace, Laura A. Poole-Warren, Conducting polymers for neural interfaces: Challenges in developing an effective long-term implant, Biomaterials, Volume 29, Issues 24–25, August–September 2008, Pages 3393-3399, ISSN 0142-9612
www.sciencedirect.com.ezproxy2.library.drexel.edu/science/article/pii/S0142961208003220?np=y
http://onlinelibrary.wiley.com/doi/10.1002/1097-4636(200108)56:2%3C261::AID-JBM1094%3E3.0.CO;2-I/full
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