Application of Nanoelectronics in Controlling Epilepsy

IJSTE - International Journal of Science Technology & Engineering | Volume 2 | Issue 07 | January 2016 ISSN (online): 2349-784X

Application of Nano Electronics in Controlling Epilepsy ArjunRaj K.B Sree Narayana Guru College of Engineering and Technology Chalakode P.O,Payyanur,Pin:670307

AswinRaj K.B Sree Narayana Guru College of Engineering and Technology Chalakode P.O,Payyanur,Pin:670307

Abstract Epilepsy is one of the diseases which seem as a terrifying one from time immemorial onwards. This is one of the diseases which human beings are afraid of and prone to so many superstitions. The basic cause of epilepsy is the seizure activity that triggers abnormal electric pulses which passes through the nervous pathways to sensors causing epilepsy. By controlling those uncontrolled electric pulses we can control epilepsy to a comfortable extend. We intends to make a simplified design of a nanoelectronic device that can do the desired work with an auxiliary nano-circuit for constantly recording the seizure activity in brain and safety measures to be adopted if any devices are found faulty. In this review we integrate biological element with nanoelectronics because we are really integrating it to living cells, this field is called as nano-bioelectronics.

Keywords: Epilepsy, Extracellular Matrix, Nano-Electronic Devices, Transfer Function, Sensor, Seizures ________________________________________________________________________________________________________

I. INTRODUCTION Epilepsy is a group of neurological disorders characterized by epileptic seizures.

Peculiarity about brain cell is that, the internal cellular interactions ultimately determine the number and type of surface proteins on brain cells. The relationship between genetic and epigenetic factors is very less known due to the complexity of interacting variables.

Certain configurations lead to a neuronal hypersensitivity to stimulus which leads to positive outward propagation of neuronal firing. That is, a seizure occurs when normal electric balance of brain is lost and misfiring of brain nerve cells occur.

During seizure, the uncontrolled signals travel towards sensory organs and the affected person shows adverse effect on consciousness, perception and movement1.

We are trying to find a solution for the problems such as what are the ways by which we can control the abnormal flow of electric flow in brain cells and the nano electronic device which can be used for this purpose with integration of biological elements and also included steps of constant analyses which help to determine which device will be faulty and the actions to be taken for the same.

II. MATERIALS AND METHODS Where Nano- Electronic Control Devices Are Inserted?

We select Extracellular matrix as the target area.

Extracellular matrix which is derived from both neurons and glial cells, are secreted and accumulate in the extracellular space to regulate various aspects of pre and postsynaptic differentiation and most important properties 8 A large number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extracellular matrix affects virtually all aspects of nervous system development and function8.

Synapses are surrounded by mesh network secreted by neurons and astrocytes. In central nervous system, the ECM make perineuronal nets enwrapping neuronal bodies and processes, which affect their development and function 9.

Figure Above shows the ECM changes at CNS (Central Nervous System) synapses. Synapses are embedded into an ECM meshnetwork(blue) 9 Then the terminal of nanoelectronic transistor inserted is in Extracellular Matrixes (ECM) which is a collection of extracellular molecules secreted by cells that provides structural and biochemical support to surrounding cells.

The cell adhesion, cell to cell communication and differentiation are common functions of ECM. The device when fixed on ECM ultimately will change the voltage at that point in relation to the cell when abnormality arises.

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Application of Nano Electronics in Controlling Epilepsy (IJSTE/ Volume 2 / Issue 07 / 011)

Fig. 1: Courtesy to the Scripps Research Institute, Department of Cell biology

Desired Type of Circuit Needed in Controlling Epilepsy The main cause of epilepsy is certain configurations in brain leading to a neuronal hypersensitivity to stimulus which leads to positive outward propagation of neuronal firing. That is, a seizure occurs when normal electric balance of the brain is lost and misfiring of brain nerve cells occur.

We need a steady state device. That is the circuit needs to allow normal flow of electricity but block the abnormal flow of electricity. This circuit should be invisible to the normal activity of the brain so that it can operate as normal.

In short we need a dampening circuit such as a filter.

Methodology of designing such a Filter Circuit for Controlling Purpose The Filter We need to describe the filter mathematically and find the least amount of transistors for it.

We adopt transfer function calculation to design according to environment in brain that transfers electric signals, by which we can get the number and arrangement of transistors. And we have to do experiments on brain to get the parameters required in finding that desired transfer function required.

First of all we should find out the transfer function that cancels out the abnormal electrical activity.

Way of designing this filter There are three main fundamental components which wrap up a nanocircuit; these are transistors, interconnections and architecture.

Indian scientists have recently developed the world’s smallest transistor which will be used for nanocircuits 15.

A recent discovery shows nanotubes are capable of building up a transistor which has characteristics of two branches that will give a Y shape and current can flow through both branches, which can be controlled via an third branch which will turns the voltage on and off which led to the discovery of true nanocircuits15.This discovery make drastic change logic circuits need metal gates to control the flow of electric current.

Primary stage simulation and analyzing of nanoscale control circuit model First we lab test the nanocircuit model we trying to implement with usual practice of using Cadence DFII software package16.

Making of actual nano electronic control circuit that can be practically implement a) First challenge: Sensing the appropriate location to fix the nanoelectronic circuit units

Here we require biosensing operation for sensing the Extracellular matrix region. For that purpose we are implying combination of biological elements with electronics. The research field regarding this is called Bioelectronics. Scientists already successfully made combination of biological elements with electronic units for sensor applications. One example is that glucose oxidase on an oxygen electrode.

So like that we build a nanobioelectronic sensor 21 that will sense the Proteoglycans19, which is a group of glycosaminoglycans, negatively charged polysaccharide chains.

Reason we use a sensor to sense Proteoglycans because of two reasons First reason is it is the major components of extracellular matrix 19. Second reason is it is attached to negatively charged polysaccharide chains so that sensing is easy. That is the concept of electrical detection of biological interaction that will make conductance variation of nanometer size-sensor 18.

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Application of Nano Electronics in Controlling Epilepsy (IJSTE/ Volume 2 / Issue 07 / 011)

b) Second challenge: Preventing from attachments to undesired locations

In this case we use a Novel drug delivery system11,23this will make the nanobioelectronic devices to get into brain ECM (Extracellular matrixes) via blood which will be least invasive method that is drug will act as a carrier. As 98 percent of all drugs targeting brain are blocked by this blood brain barrier The system use a Coe material comprising a drug and a hydrophobic like property and these methods will enhance efficiency.

Novel methods 10 aim to deliver accurate delivery of nanobioelctronic device to the seizure focus or foci. Drug eluting wafers could be surgically positioned over an epilptogenic region of brain.

Nanobioelectronic device can be delivered to seizure focus by an implanted catheter and subcutaneous pump. Inactive nanobioelectronic device must have biosensor 20 to be active only at the seizure focus (nanobioelectronic sensor) and adhere to ECM (Extra Cellular Matrix) with locally –released substances.

Liposomes and polysomes are makes as slow release storage vehicles for drugs. Targeting components can hold liposomes near a region of interest, provided that they can penetrate the blood brain barrior 10.

This method is least invasive method of delivery of nanobioelectronic devices.

Auxiliary Circuit Needed for Nanoelectronic Control Circuit: Nanocircuit to Analyze Seizure Analysis Even though we employ controlling nanocircuits to control the abnormal electrical activity in brain cells, we need auxiliary circuits to analyse if it works well or not. It can be done by analysing the electrical activity in brain cells via censors.

Current advancements used for Brain wave analysing This field comes under a broad category known as brain – computer interface (BCI)  Brain-computer interface (BCI) is a computer-based technology that allows the brain to communicate with external devices in order to restore, assist, or augment cognitive, sensory, and/or motor functions. BCI research began in the 1970s under a grant from the NSF followed by a contract from DARPA. BCI research was initially conducted on animals. The first BCI prosthetic device was implanted in humans in the mid-1990s.  EEG-based BCI is the most studied and perhaps the most clinically promising BCI technology.  Advantages: non-invasive, superior temporal resolution, ease of use, portability, and low set-up cost.  Disadvantages: susceptibility to noise, extensive user training is required. Other BCI signals that were employed include evoked potentials, MEG, and MRI. Evolution of BCI technology in integrating with brain is shown in figure 6 below,research is conducting to find efficient one

Fig. 2: BCI technology in integrating with brain

Circuit design for recording brain electrical activity with nanoelectronic application (not found till now) Brain waves are tiny analogue signals (electric potentials) that are usually recorded on the scalp with dry electrodes .These signals induce tiny electronic currents in the wires that connect to nanoscale made AVR microcontroller (One of the first microcontroller families to use on chip flash memory for program storage) 14. The nanoscale AVR microcontroller (research is going on to built that one) is the controller, it reads value from analogue source and writes to flash memory which stores programme. Then flash memory can be connected to an IEEE 1451, (which is a set of smart transducer interface standards describes a set of open, network independent communication interfaces for connecting transducers to microprocessor, instrumentation systems and control networks. Goal of 1451 is to allow the access of transducer data through a common set of interfaces whether the transducer connected to systems or networks via a wireless means)12,13which can connected wirelessly to a transducer which will show the recorded info info on screen. So a person with installed devices like this can monitor the working condition of installed epilepsy control device periodically Installing of auxiliary analysing circuits Apply these circuits in scalp region of head; we can monitor the electric activity inside brain by dry electrodes.

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Application of Nano Electronics in Controlling Epilepsy (IJSTE/ Volume 2 / Issue 07 / 011)

The most important Character of these dry electrodes is that it provides a stable low noise electrical interface of low impedance barely penetrating outer skin layer 22, which results in a pain free and lowers the risk of infection rate and is so low invasive.

Procedure followed to unfit the device from locations when connected nanobioelectronic device find damaged.

The connected nano-electronic devices may get damaged somehow after some time and it may cause an adverse effect on brains normal working So we can use RF nanoreceiver 17.that means we can use a charged carbon nanotube17,22, so that under RF (Radio Frequency) exposure it will get unfit from the locations and biological elements that integrated with them make them dissolve with blood. So by the way it can be removed out easily.

And research is to be done on taking that waste particle out of the brain membrane.

Currently used application of Nano electronics for analysing brain electric activity in a precise manner Bio-integrated devices have played a major role in the research and treatment of epilepsy. It is called as ‘’Multiplexed Intracellular Action Potential Recording’’. Recording of electrical activity with surface contact electrodes helps in the understanding of neural activity.

To get high resolution result it must cover a larger area so as to get accurate brain activity. So the electrodes are placed under the Dura membrane and the electrodes also have contacts with cortical surfaces 3.

Fig. 3: courtesy to Nature publishing group

Figure 3: inserting electrodes to analyzing uncontrolled electric signals caused by seizure

Fig. 4: Flexible brain -computer interfaces (fBCIs)

Thickness of electrode is made in nano range and is connected in mesh geometry. The mechanical means to carry those nanoelectronic systems to their destination should meet the challenge of extremely low bending property, so special sacrificial carriers are used like silk that will dissolve in bio fluids. So when deployed, the substrates that carry the nano-electronic systems dissolves in bio fluids and make the ultra thin mesh of electrodes in every minute curved regions of brain surface. Limitation of this type of application is, this method can only be used to analyse brain electric activity during a seizure, and it does not actually do anything to control that abnormal electric flow between brain cells

III. CONCLUSION Here we designed steps to make a nanoelectronic control circuit that can be used to control the abnormal electric activity after seizure occurs.

And also here we integrate the biological elements with nanoelectronic circuits so it will be effective in sensing the appropriate locations for fixing to occur.So it can be called as nanobioelectronic circuit And here we designed a nearly noninvasive method of transferring that nanobioelectronic device to desired locations by reffering to recent research done about it.

And for analyzing the proper working of the control device we implant an auxiliary circuit consist of nano electrodes in scalp region connected wirelessly to a transducer which will show the recorded info info on screen And if we found any fault on the connected nanobioelectronic circuit by auxiliary circuit,we can dispatch the device from location via RF signal which can be sensed by charged carbon nanotube in the nanobioelectronic control circuit.

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Application of Nano Electronics in Controlling Epilepsy (IJSTE/ Volume 2 / Issue 07 / 011)

So here we apply a nanobioelectronic control circuit to control the abnormal electric activity in ECM and connected an auxiliary circuit to analyse the proper working and also provide steps to fit the device on desired location and unfit from the locations.

As nanobioelectronic devices interface with human brain we are literally making cyborgs.So this led to new field of interest that will really need to develop in near future to compete against all odds human race facing in health fields

ACKNOWLEDGEMENT Acknowledges support from Prof.Reetha of electrical engineering department and all other professors of Sree Narayana Guru College of Engineering and Technology

ACRONYM LIST ECM: Extra cellular matrix FET: Field effect transistor CNS: Central Nervous System RF: Radio Frequency MEG: Magnetoencephalography MRI: Magnetic resonance imaging

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