The Success of Polypyrrole Based Neural Sensors

By Tyler Shewbert

Abstract

            The study of neural activity can be performed with implanted electrodes. One of the major drawbacks that researchers face when using typical flat, metal electrodes is that the impedance caused by the growth of scar tissue around the implant renders the collection of data impossible within weeks [1-4]. A proposed solution is to develop electrodes that have been organically enhanced using polymers and peptides that would allow the electrode and neurons to have a more intimate connection that would last longer. The polymer polypyrrole (Ppy) and various peptides were added to metallic conductors of gold and iridium by a team at the University of Michigan. They were found to improve the implanted electrode’s ability to study neural activity [1-4]. The success of this research shows that the use of organic electrodes for the study of neural activity is possible and potentially better than their non-organic counterparts.

Introduction

            An electrode is a basic electrical device used for conduction. When used as neural sensors, they are implanted [4]. However, for neural applications, flat, metallic electrodes are surrounded by scar tissue caused by inflammation. This renders the device useless within a matter of weeks due to the increasing impedance caused by scarring [1-3].

To improve and optimize such sensors three things are needed: Improved capacitance, convex surfaces, and better biocompatibility [3]. Low impedance is necessary when an electrode is being used to measure neural signals [3]. The capacitance between the electrode and the area where it is implanted is modelled as in series with the impedance caused by the tissue. Therefore, by increasing the capacitance of the electrode, the electrodes efficiency can be increased [3]. Convex surfaces would allow electrodes to form more intimate connections with the tissue around the implant [3]. Iridium and gold have both been used electrode contacts for neural sensors because of their known biocompatibility [3]. Unfortunately, long-term recordings using these devices fail [3].

Electroactive polymers and peptides have shown promising results in modifying electrodes to improve all three of these areas. Ppy is an organic, conducting polymer [4]. Ppy in combination with the synthetic peptide DCDPGYIGSR was found to improve the results of in vitro neural recordings within guinea pigs [1]. Ppy was also used in conjunction with the nonapeptide CDPGYIGSR to improve the surface of the electrode to enhance its ability to connect with the surrounding tissue [2]. The use of Ppy in combination with various other biological materials was shown to increase the area of connection between the neuron and electrode, increasing capacitance and reducing impedance [1-4].

Results and Discussion

David Martin and his team at the University of Michigan published a series of papers about using organic materials to enhance implantable neural electrodes capabilities. They first began by exploring how Ppy doped with polystyrene sulfonate (PSS) could be used to change the topology of the electrode [3]. Next, they examined how Ppy and the peptides could be used to increase the attraction of neural filaments to the electrode. They found that using this combination allowed them to gain the desired convex shape that would improve connection between the electrode and the surrounding tissue [2]. Finally, they made electrodes which were composed of Ppy and the synthetic peptide DCDPGYIGS. They implanted these within guinea pigs to study whether or not the changed surfaces improved data recording when compared to a control group of guinea pigs implanted with flat-surfaced electrodes, and also tested the environmental effects on the electrodes using deionized water [1, 4].

In the first paper, the combination of Ppy and PSS was grown onto neural electrodes made of either Au or Ir [3]. The structure of the Ppy/PSS on the electrode was controlled precisely and reproducibly by a charge passing through the system [3]. The topology of the structure was complex enough that the efficient surface area for a Ppy/PSS film was estimated to be 26 times greater than the surface area for a flat gold electrode. As this surface area increased, the capacitance increased [3]. Impedance spectroscopy showed that the coated electrode had impedance values of one to two times less than that of a flat Au electrode [3]. Thickness of the film was varied from 5 to 20 mm. The best thickness for the film was found to be 13 mm [3]. Neural implementation of the electrodes within guinea pigs showed that a Ppy/PSS coated electrode could record high-quality neural data [3]. The ability to reduce the impedance by as much as two orders of magnitude and the ability to increase the surface area by 26 times proved neural electrodes efficiency could be improved by the addition of polymers.

The team then examined the possibility of adding biomaterials to the Ppy film in hopes of increasing the development of the connection between the tissue and the electrode [2]. The nonapeptide CDPGYIGSR and fibronectin fragments (SLPF) were added to the Ppy film [2]. Impedance spectroscopy once again showed that the impedance for the Ppy/SLPF material was an order of magnitude lower at the biologically important frequency of 1 kHz [2]. Next, glial cells from rats and neuroblastoma cells were grown on electrodes both with and without biological coating [2]. The Ppy/SLPF coating attached to the glial cells and the Ppy/CDPGYIGSR attached to the neuroblastoma cells better than the control groups of electrodes without biological coating [2]. The results also verified the idea that a convex, highly complex morphology between the tissue and the electrode was the best for establishing a connection between the two [2]. The most important result out of this paper was the ability to add cell-binding biomaterial to the polymer film to increase the chance that a well-developed connection between the tissue and the electrode could be established.

The teams third paper in 2003 studied the long-term effects of the film-enhanced electrode in the environment and its ability to record data over the period of several weeks [1]. Ppy and a synthetic peptide DCDPGYIGSR were now used as the film deposited on Au  [1]. First, the electrodes were soaked in de-ionized water for several time periods up to seven weeks [1]. It was found that the peptides did not diffuse after seven weeks, which had been a major concern [1]. After to probes had been soaked for seven weeks, they were then implanted in guinea pigs [1]. A control group of guinea pigs also had non-coated electrodes implanted [1]. The impedance was measured at 1 kHz at one week, two weeks and three weeks [1]. Recording of data was also performed periodically [1]. The electrodes were also stained for microfilaments to show the amount still connected between the neurons and the electrodes [1].  The following table summarizes the results:

Table 1. Comparison of the results of the coated and non-coated electrodes implanted in guinea pigs (data from [1])

From Table 1, the importance of the filaments being connected and the ability for electrodes to record data is obvious. The ability for the electrode to maintain recordings is directly related to the number of filaments are still connected [1]. The main advantage using biologically enhanced electrodes is in recording neural data. It would be interesting to see the results of a study that compared the neural filament connections for a Ppy/PSS film versus a film enhanced with Ppy/DCDPGYIGSR to see how much of an effect the peptide has on enhancing the connection.

Outlook and relevance of work

            The University of Michigan team has shown that the for neural sensing, biologically enhanced electrodes are more effective than their non-coated counterparts. The ability to implant neural sensors that have longer lifetimes has the advantage of being able to perform long-term studies on neural activity and reducing the need for surgery to implant the electrodes. The lower impedance that is seen for the first two weeks, as in the third study, allows for a more accurate collection of data. Further studies can reveal even better peptides than promote connectivity between neurons and the electrodes, potentially for longer periods of times. Various other polymers are being studied also such as polythiophene, poly(3,4-ethylenedioxythiophene) (PEDOT), and polyaniline [5]. Further research on the potential toxicity of such electrodes is needed before large-scale human studies can be performed. Results from a 2009 study of a PEDOT based electrodes showed no toxic effects in rats [6]. While bioelectronic solutions might not solve all the problems they are being applied to, it seems that organically enhanced electrodes for neural sensing is the correct solution, but further refinement is necessary.

References

[1] Cui X, Wiler J, Dzaman M, Altschuler RA, Martin DC. In vivo studies of polypyrrole/peptide coated neural probes. Biomaterials. 2003;24:777-87.

[2] Cui X, Lee VA, Raphael Y, Wiler JA, Hetke JF, Anderson DJ, et al. Surface modification of neural recording electrodes with conducting polymer/biomolecule blends. Journal of biomedical materials research. 2001;56:261-72.

[3] Cui X, Hetke JF, Wiler JA, Anderson DJ, Martin DC. Electrochemical deposition and characterization of conducting polymer polypyrrole/PSS on multichannel neural probes. Sensors and Actuators A: Physical. 2001;93:8-18.

[4] Berggren M, Richter‐Dahlfors A. Organic bioelectronics. Advanced Materials. 2007;19:3201-13.

[5] Guimard NK, Gomez N, Schmidt CE. Conducting polymers in biomedical engineering. Progress in Polymer Science. 2007;32:876-921.

[6] Asplund M, Thaning E, Lundberg J, Sandberg-Nordqvist A, Kostyszyn B, Inganäs O, et al. Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrodes. Biomedical Materials. 2009;4:045009.