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

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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

Schematic

3D microarray

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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

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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

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THANK  YOU  

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