Here, we describe a novel dual microelectrode concept based on brain oxygenation that can be used to predict seizures caused due to traumatic brain injury. Since brain oxygenation occurs slightly prior to chaotic neural firing, it can be used to predict in advance the occurrence of a seizure.

1. 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/

2. 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

3. 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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4. 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?

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. Schematic
3D microarray
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14. 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

15. 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

16. Ways to Prevent Oncoming Seizures9
www.bedfordlabs.com/content/dam/internet/opu/bedfordlabs/com_EN/
images/products/midazolam/MID%20combo%20lg.jpg
http://ativan-howto.com/wp-content/
uploads/2012/03/2-1.jpg
http://
1boringoldman.com/
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

17. 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

18. 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

19. 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
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20. 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

21. THANK
YOU
https://soundcloud.com/naambeatz/mind-control