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<h1 id="Introduction">MEMBRANE</h1> | <h1 id="Introduction">MEMBRANE</h1> | ||
− | <p><i>When manipulating genetically engineered organisms, it is crucial to guarantee the confinement of these organisms. In our case, we want | + | <p><i>When manipulating genetically engineered organisms, it is crucial to guarantee the confinement of these organisms. In our case, we want genetically modified bacteria to stay at the interface between the prosthesis and the external organic medium. At the same time, one of the main issues our project wants to tackle is the conduction of the neuron influx to the prosthesis. The answer to these questions came as a double solution: confinement of the bacteria by conductive nanoporous membranes. The membrane’s nanoporosity allows substances produced by our modified biofilm to pass through the membrane, but the bacteria remain confined. We tested the conductivity and biocompatibility of two types of membranes.</i></p></div> |
<div class="block two-third center"> | <div class="block two-third center"> | ||
<img src="https://static.igem.org/mediawiki/2018/d/df/T--Pasteur_Paris--Membrane-intro.png"> | <img src="https://static.igem.org/mediawiki/2018/d/df/T--Pasteur_Paris--Membrane-intro.png"> | ||
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<div class="block title"><h3 style="text-align: left;" id="Polymer">Polymer-coated membranes</h3></div> | <div class="block title"><h3 style="text-align: left;" id="Polymer">Polymer-coated membranes</h3></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>The other membranes were Sterlitech Alumina Oxide Membrane Filters with 0.2 micrometer pores. Their higher rigidity compared to the gold-coated membranes led to several membranes being broken while manipulating them with a forceps. We used these membranes as a support for different conductive and biocompatible polymers: PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate), PEDOT:Cl and PEDOT:Ts. </p> | + | <p>The other membranes were Sterlitech Alumina Oxide Membrane Filters with 0.2-micrometer pores. Their higher rigidity compared to the gold-coated membranes led to several membranes being broken while manipulating them with a forceps. We used these membranes as a support for different conductive and biocompatible polymers: PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate), PEDOT:Cl and PEDOT:Ts. </p> |
</div> | </div> | ||
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<div class="block full"> | <div class="block full"> | ||
− | <p>For PEDOT:PSS, an aqueous solution of PEDOT:PSS was prepared ([1]) and alumina oxide membranes were dipped for 24 hours in this solution. Electron microscopy of the membranes before and after the experiment showed the deposit of a substance on their surface; however its nature has not been tested.</p> | + | <p>For PEDOT:PSS, an aqueous solution of PEDOT:PSS was prepared ([1]) and alumina oxide membranes were dipped for 24 hours in this solution. Electron microscopy of the membranes before and after the experiment showed the deposit of a substance on their surface; however, its nature has not been tested.</p> |
</div> | </div> | ||
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<div class="block title"><h1>Nerve modelisation</h1></div> | <div class="block title"><h1>Nerve modelisation</h1></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>As seen in the other parts of this wiki, we chose to use | + | <p>As seen in the other parts of this wiki, we chose to use a nanoporous membrane in our device. The first goal of the membrane was to confine our biofilm, so it does not escape the prosthesis. Moreover, we also used our membrane as a conductive electrode. This solution was interesting since we didn’t have enough time to develop an entire electrical device which collects and treat the signal of the nerves. However, we know we still need to improve our interface if we want the patient to fully control his prosthesis. That is why we decided to look at what is already made in this field. So, first, we detailed how it is possible to model the electrical characteristics of a nerve. Then, we searched for information on electrodes and signal treatment. </p> |
</div> | </div> | ||
<div class="block full bothContent"> | <div class="block full bothContent"> | ||
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<img src=""> | <img src=""> | ||
<div class="legend"><b>Figure 1: </b>Schematic of a nerve cuff electrode. Retrieved on Oct. 14th from MicroProbes for Life Science<sup>[1]</sup></div> | <div class="legend"><b>Figure 1: </b>Schematic of a nerve cuff electrode. Retrieved on Oct. 14th from MicroProbes for Life Science<sup>[1]</sup></div> | ||
− | <p>The activity recorded by the cuff electrode represents the simultaneous activity of a large number of active axons. The potential of action seen by the electrode | + | <p>The activity recorded by the cuff electrode represents the simultaneous activity of a large number of active axons. The potential of action seen by the electrode is overlapped, allowing only a "global" image of the activity inside the nerve. As a result, the selectivity of the recording is limited by the number of axons undergoing simultaneous discharge and by the position and surface of the contact of the cuff electrode. This type of measurement, therefore, does not allow the identification of fiber activity alone.</p> |
− | <p>Increasing the number of electrode poles allows | + | <p>Increasing the number of electrode poles allows increasing the selectivity of this type of electrode. A multi-pole cuff electrode is then called a cuff electrode having more than three contacts. These contacts can be rings or segments of rings.</p> |
</div> | </div> | ||
<div class="block title"><h3 style="text-align: left;">3. FINE electrode:</h3></div> | <div class="block title"><h3 style="text-align: left;">3. FINE electrode:</h3></div> | ||
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<div class="block title"><h3 style="text-align: left;">2. Envelope extraction:</h3></div> | <div class="block title"><h3 style="text-align: left;">2. Envelope extraction:</h3></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>Rectification and Bin-Integration (RBI) of the nerve raw signal is widely used in rehabilitation application. This point of RBI ENG | + | <p>Rectification and Bin-Integration (RBI) of the nerve raw signal is widely used in rehabilitation application. This point of RBI ENG is found by calculating the average of the absolute value of ENG samples spread over a given period of time. This period is called “bin” and its value depends on the application. It ranges from 10 ms to 200 ms. The smoothed envelope-like signal created by RBI makes it easy to extract information about the innervated organ.</p> |
</div> | </div> | ||
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<div class="block title"><h3 style="text-align: left;">1. ENG-EMG selectivity:</h3></div> | <div class="block title"><h3 style="text-align: left;">1. ENG-EMG selectivity:</h3></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>The body is made so that a nerve is never very far from a muscle. However, the triggering and control of muscle contractions | + | <p>The body is made so that a nerve is never very far from a muscle. However, the triggering and control of muscle contractions use a similar mechanism to the propagation of nerve impulses. Thus, the vicinity of a muscle is the seat of important extracellular currents because of the large number of muscle fibers excited simultaneously. The potential differences associated with these currents are called EMG, for electromyogram. Action potentials in muscle have mV amplitude, larger than a neural signal, and their spectra overlap. Minimizing these forms of interference is there for essential.</p> |
− | <p>In order to attenuate the EMG signal, tripolar cuff electrode are used (Cf. Figure 3). For the nerve signal, the main point of the cuff is that it reduces the volume of tissue in which the action currents flow and, therefore, increases the potential differences between the electrodes. For the EMG interference, the fact that the cuff is a tube of uniform cross-sectional area means that the gradient inside, due to each external source, is approximately constant and, therefore, the potential differences between the pairs of electrodes are equal and cancel. How they are | + | <p>In order to attenuate the EMG signal, tripolar cuff electrode are used (Cf. Figure 3). For the nerve signal, the main point of the cuff is that it reduces the volume of tissue in which the action currents flow and, therefore, increases the potential differences between the electrodes. For the EMG interference, the fact that the cuff is a tube of uniform cross-sectional area means that the gradient inside, due to each external source, is approximately constant and, therefore, the potential differences between the pairs of electrodes are equal and cancel. How they are canceled depends on the amplifier configuration but the principle is that out-of-cuff signals are canceled while neural signals do not.</p> |
<p>The variation of the ENG is not linear over the entire length of the electrode, it is at a maximum in the center of the cuff. Moreover, the average value of the EMG potential is zero or close.</p> | <p>The variation of the ENG is not linear over the entire length of the electrode, it is at a maximum in the center of the cuff. Moreover, the average value of the EMG potential is zero or close.</p> | ||
<p>Thus, the impact of EMG on the measurement is significantly attenuated, while the ENG is preserved</p> | <p>Thus, the impact of EMG on the measurement is significantly attenuated, while the ENG is preserved</p> | ||
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<div class="block full"> | <div class="block full"> | ||
<p>Methods aim to increase the spatial selectivity of extra-neural electrodes to discriminate active fascicles, in order to determine the activity of each nerve branch.</p> | <p>Methods aim to increase the spatial selectivity of extra-neural electrodes to discriminate active fascicles, in order to determine the activity of each nerve branch.</p> | ||
− | <p>One way to increase the spatial selectivity is to increase the number of | + | <p>One way to increase the spatial selectivity is to increase the number of measurement points. The issue is to separate the sources. In this context, in order to increase the spatial selectivity of the extra-neural electrodes, the multipolar cuffs or FINE electrode have been designed. These structures make it possible to increase the number of contacts, thus the number of measured signals.</p> |
<p>Another way is to use algorithms. Blind source separation techniques are able to decompose fascicular signals from FINE electrodes. Several other methods have been described in the literature. They aim to localize or separate nerve trunk signals. For instance, Neurofuzzy algorithms use an artificial neural network.</p> | <p>Another way is to use algorithms. Blind source separation techniques are able to decompose fascicular signals from FINE electrodes. Several other methods have been described in the literature. They aim to localize or separate nerve trunk signals. For instance, Neurofuzzy algorithms use an artificial neural network.</p> | ||
− | <p>We can also mention the method based on antenna array beamforming. This seems to be one of the most advanced | + | <p>We can also mention the method based on antenna array beamforming. This seems to be one of the most advanced methods to distinguish fascicular activity inside a nerve. It would be possible to distinguish up to five active fascicles at the same time.</p> |
</div> | </div> | ||
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<div class="block title"><h3 style="text-align: left;">3. Electrode sizing</h3></div> | <div class="block title"><h3 style="text-align: left;">3. Electrode sizing</h3></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>n order to increase neural information relative to the noise, it is vital to optimize the cuff dimensions. The literature suggests that the best compromise between cuff length and available place is a cuff length close to the wavelength of the transmembrane action potential. This one is approximately linear with fiber diameter.</p> | + | <p>n order to increase neural information relative to the noise, it is vital to optimize the cuff dimensions. The literature suggests that the best compromise between cuff length and the available place is a cuff length close to the wavelength of the transmembrane action potential. This one is approximately linear with fiber diameter.</p> |
− | <p>According to Struijk, the action potential propagation velocity can be approximated as 55.800 nodes/s and the duration, of the transmembrane action potential is approximately 0,4 ms.</p> | + | <p>According to Struijk, the action potential propagation velocity can be approximated as 55.800 nodes/s and the duration, of the transmembrane action potential, is approximately 0,4 ms.</p> |
− | <p>Thus, to have an optimal measurement, the cuff electrode must cover 22 nodes of Ranvier. The inter-pole distance must therefore be adjusted to h = 11 lmy (lmy is the length of myelin separating two nodes of Ranvier). So, for a typical fiber, the inter-electrode distance h should be about 1 cm, which is used in most ENG measuring electrodes.</p> | + | <p>Thus, to have an optimal measurement, the cuff electrode must cover 22 nodes of Ranvier. The inter-pole distance must, therefore, be adjusted to h = 11 lmy (lmy is the length of myelin separating two nodes of Ranvier). So, for a typical fiber, the inter-electrode distance h should be about 1 cm, which is used in most ENG measuring electrodes.</p> |
<img src=""> | <img src=""> | ||
<div class="legend"><b>Figure 7: </b>Extra-neural potential of monopolar action according to the position of the measuring point. The diagram at the top left shows the simulated situation. At the top right, the simulation corresponding to this configuration is represented: calculation of twice five monopolar potentials, for a typical axon (diameter of 8.7 μm, and lmy= 1 mm). The distances from this axon to the measurement points are ρ1=100 μm for site A and ρ2=500 μm for site B. Below, the monopolar signals at points “a” to “e” are shown for each of the measurement sites.</div> | <div class="legend"><b>Figure 7: </b>Extra-neural potential of monopolar action according to the position of the measuring point. The diagram at the top left shows the simulated situation. At the top right, the simulation corresponding to this configuration is represented: calculation of twice five monopolar potentials, for a typical axon (diameter of 8.7 μm, and lmy= 1 mm). The distances from this axon to the measurement points are ρ1=100 μm for site A and ρ2=500 μm for site B. Below, the monopolar signals at points “a” to “e” are shown for each of the measurement sites.</div> | ||
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<div class="block title"><h3 style="text-align: left;">4. Local variations of the potential</h3></div> | <div class="block title"><h3 style="text-align: left;">4. Local variations of the potential</h3></div> | ||
<div class="block full"> | <div class="block full"> | ||
− | <p>The spatial low frequencies of the electric field generated by an active axon, has almost the same amplitude at each point of the nerve surface, regardless of the location of the axon inside the nerve. Conversely, the amplitudes of the high-frequency components of this electric field | + | <p>The spatial low frequencies of the electric field generated by an active axon, has almost the same amplitude at each point of the nerve surface, regardless of the location of the axon inside the nerve. Conversely, the amplitudes of the high-frequency components of this electric field depending on the distance between the axon and the point of observation.</p> |
<p>It was possible for several poles placed online, to determine the depth of the axon. Indeed, for axons close to the surface of the nerve, there is a difference in amplitude (as a function of the relative position of each pole relative to that of Ranvier's nodes), while for those who are far from the surface the measured amplitude is the same for each of the poles (Cf. Figure 7). Thus, it is necessary to suppress the common mode and amplify only the difference of the signals collected on several poles.</p> | <p>It was possible for several poles placed online, to determine the depth of the axon. Indeed, for axons close to the surface of the nerve, there is a difference in amplitude (as a function of the relative position of each pole relative to that of Ranvier's nodes), while for those who are far from the surface the measured amplitude is the same for each of the poles (Cf. Figure 7). Thus, it is necessary to suppress the common mode and amplify only the difference of the signals collected on several poles.</p> | ||
</div> | </div> | ||
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<div class="block separator-mark"></div> | <div class="block separator-mark"></div> | ||
− | <div class="block full"><p><b>Thus, thanks to this example, we understand it is possible to develop our own type of electrode. We gathered a lot of different information. First, having a good electrical model of the nerve is crucial to understand what are the parameters we need to take into account to develop our electrode. Moreover, it is primordial in order to be able to simulate the performance of an electrode. We now know that different algorithms that improve the output signal of an electrode already exist. We would like to test and use such algorithms for our device. Finally, thanks to the example of the FORTE electrode, we have already thought about how it will be possible to incorporate such an electrode in our device.</b></p></div> | + | <div class="block full"><p><b>Thus, thanks to this example, we understand that it is possible to develop our own type of electrode. We gathered a lot of different information. First, having a good electrical model of the nerve is crucial to understand what are the parameters we need to take into account to develop our electrode. Moreover, it is primordial in order to be able to simulate the performance of an electrode. We now know that different algorithms that improve the output signal of an electrode already exist. We would like to test and use such algorithms for our device. Finally, thanks to the example of the FORTE electrode, we have already thought about how it will be possible to incorporate such an electrode in our device.</b></p></div> |
<div class="block separator-mark"></div> | <div class="block separator-mark"></div> | ||
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<ul style="text-align: left;"> | <ul style="text-align: left;"> | ||
<li></li> | <li></li> | ||
− | <li style="list-style-type: decimal;">MicroProbes for Life Sciences, | + | <li style="list-style-type: decimal;">MicroProbes for Life Sciences, « Nerve Cuff Electrodes ». Retrieved Oct. 14th, 2018 from https://microprobes.com/products/peripheral-electrodes/nerve-cuff</li> |
<li style="list-style-type: decimal;">Yoo, P. B., & Durand, D. M. (2005). Selective Recording of the Canine Hypoglossal Nerve Using a Multicontact Flat Interface Nerve Electrode. IEEE Transactions on Biomedical Engineering, 52(8), 1461–1469. doi:10.1109/tbme.2005.851482</li> | <li style="list-style-type: decimal;">Yoo, P. B., & Durand, D. M. (2005). Selective Recording of the Canine Hypoglossal Nerve Using a Multicontact Flat Interface Nerve Electrode. IEEE Transactions on Biomedical Engineering, 52(8), 1461–1469. doi:10.1109/tbme.2005.851482</li> |
Revision as of 17:17, 15 October 2018
MEMBRANE
When manipulating genetically engineered organisms, it is crucial to guarantee the confinement of these organisms. In our case, we want genetically modified bacteria to stay at the interface between the prosthesis and the external organic medium. At the same time, one of the main issues our project wants to tackle is the conduction of the neuron influx to the prosthesis. The answer to these questions came as a double solution: confinement of the bacteria by conductive nanoporous membranes. The membrane’s nanoporosity allows substances produced by our modified biofilm to pass through the membrane, but the bacteria remain confined. We tested the conductivity and biocompatibility of two types of membranes.
Membrane
Nerve modelisation
As seen in the other parts of this wiki, we chose to use a nanoporous membrane in our device. The first goal of the membrane was to confine our biofilm, so it does not escape the prosthesis. Moreover, we also used our membrane as a conductive electrode. This solution was interesting since we didn’t have enough time to develop an entire electrical device which collects and treat the signal of the nerves. However, we know we still need to improve our interface if we want the patient to fully control his prosthesis. That is why we decided to look at what is already made in this field. So, first, we detailed how it is possible to model the electrical characteristics of a nerve. Then, we searched for information on electrodes and signal treatment.