Acta Biomaterialia xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat
The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications Sungchul Baek, Rylie A. Green ⇑, Laura A. Poole-Warren Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
a r t i c l e
i n f o
Article history: Received 21 January 2014 Received in revised form 26 March 2014 Accepted 2 April 2014 Available online xxxx Keywords: Conducting polymer PEDOT Dopant choice Topography Thickness
a b s t r a c t Poly(3,4-ethylenedioxythiophene) (PEDOT) films have attracted substantial interest as coatings for platinum neuroprosthetic electrodes due to their excellent chemical stability and electrical properties. This study systematically examined PEDOT coatings formed with different amounts of charge and dopant ions, and investigated the combination of surface characteristics that were optimal for neural cell interactions. PEDOT samples were fabricated by varying the electrodeposition charge from 0.05 to 1 C cm2. Samples were doped with either poly(styrenesulfonate), tosylate (pTS) or perchlorate. Scanning electron micrographs revealed that both thickness and nodularity increased as the charge used to produce the sample was increased, and larger dopants produced smoother films across all thicknesses. X-ray photoelectron spectroscopy confirmed that the amount of charge directly corresponded to the thickness and amount of dopant in the samples. Additionally, with increased thickness and nodularity, the electrochemical properties of all PEDOT coatings improved. However, neural cell adhesion and outgrowth assays revealed that there is a direct biological tradeoff related to the thickness and nodularity. Cell attachment, growth and differentiation was poorer on the thicker, rougher samples, but thin, less nodular PEDOT films exhibited significant improvements over bare platinum. PEDOT/pTS fabricated with a charge density of 165 eV, is summarized in Table 2. pTS and ClO4 films showed a doping ratio of 0.3–0.4 dopants per monomer. The doping ratio of PSS films was 0.6–0.7. The high doping ratio is likely due to the polymeric nature of PSS. The amount of dopant in 0.05 C cm2 ClO4, pTS or PSS was 3, 4 or 12 lg, respectively, and the amount in 1 C cm2 was 82, 102, 233 lg, respectively. 3.3. Electrical performance
Fig. 6. Changes in charge storage capacity over 800 cycles.
fabrication parameter, and by the doping ion, a constituent. While there was a general observation that higher charge density resulted in bigger nodules, the overall morphology of films, especially the 1 C cm2 films, was largely influenced by the choice of dopant. At all thicknesses, PEDOT/PSS films were smoother than films doped with ClO4 or pTS. Thick PEDOT/ClO4 films exhibited nodular morphology with an average nodule diameter of 40 lm. This unique morphology is well illustrated in Fig. 2d. The 1 C cm2 PEDOT/pTS film was comprised of smaller nodules, with an average diameter of 15 lm, randomly stacked together to form a rough and irregular microstructure. Fig. 3 shows a plot comparing the thicknesses measured from cross-sectional SEM, and theoretically calculated from XPS data.
3.3.1. Charge storage capacity and electrochemical stability CPs are pseudo-capacitors that allow concurrent resistive and capacitive charge transfer. In CV, purely capacitive and resistive charge transfer mechanisms are respectively indicated by square and linear curves. The cyclic voltammograms of PEDOT films, shown in Fig. 5, were generally trapezoids, representing the combined geometry of a linear and a square waveform. One exception was PEDOT/PSS films deposited with 1 C cm2 of charge. Instead of trapezoids exhibited in other samples, thick PEDOT/PSS films showed concave curves in a negative voltage range and a distinctive oxidation peak at 50 mV and a reduction pair at 151 mV. The size and percentage loss of CSC, which respectively indicates the electrochemical performance and stability, is depicted and tabulated in Fig. 6 and Table 3. There were two general trends observed regarding the electrochemical performance of PEDOT films. Firstly, films formed with higher charge density had higher CSC. Secondly, with the exception of the 0.05 C cm2 films that had similar CSC values regardless of dopant, the CSC of a film increased in order of decreasing dopant size from PSS, pTS to ClO4. The initial CSC of 1 C cm12 ClO4 film, 150.47 ± 6.29 mC cm2,
Table 3 The initial and the final charge storage capacity (CPC) of films and corresponding loss in CSC during 800 cycles. Charge (C/cm2)
Film
Initial CSC (mC cm2)
Final CSC (mC cm2)
CSC loss (%)
1
ClO4 pTS PSS
150.47 (±6.29) 135.43 (±7.16) 100.04 (±4.30)
91.88 (±5.08) 86.71 (±3.90) 68.23 (±4.33)
38.9 ± 4.2 36.0 ± 4.4 31.7 ± 4.5
0.5
ClO4 pTS PSS
90.66 (±2.54) 81.49 (±1.37) 67.78 (±1.59)
53.34 (±1.92) 48.91 (±1.78) 46.35 (±1.03)
41.2 ± 2.7 40.0 ± 2.41 31.6 ± 2.21
0.1
ClO4 pTS PSS
21.71 (±0.39) 21.37 (±0.71) 18.62 (±1.01)
16.59 (±0.49) 15.83 (±0.38) 14.93 (±0.6)
23.6 ± 2.7 25.9 ± 3.0 19.8 ± 5.4
0.05
ClO4 pTS PSS
10.50 (±0.70) 10.43 (±0.76) 10.52 (±0.63)
7.34 (±0.45) 7.1 (±0.88) 7.84 (±0.37)
30.1 ± 6.3 31.9 ± 9.8 25.5 ± 5.7
–
Pt
1.89 (±0.43)
2.28 (±0.15)
–
Please cite this article in press as: Baek S et al. The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications. Acta Biomater (2014), http://dx.doi.org/10.1016/j.actbio.2014.04.004
S. Baek et al. / Acta Biomaterialia xxx (2014) xxx–xxx
7
Fig. 7. (a) Electrical impedance and (b) corresponding phase angle of films having different thicknesses.
was 15 times higher than that of the 0.05 C cm2, and >75 times higher than that of platinum, 1.89 ± 0.43 mC cm2. It can be seen in Fig. 6 that the CSC of the 1 C cm2 PSS film is significantly less than the CSC of the other 1 C cm2 films. This was the direct result of the non-trapezoidal cyclic voltammograms, which significantly reduced the CSC in the negative voltage range. 3.3.2. Electrochemical impedance Fig. 7a and b show the electrical impedance and corresponding phase angle measured at frequencies ranging from 1 Hz to 10 kHz. The electrical impedance was shown to decrease with increasing thickness. All CPs presented significant electrochemical advantage over platinum electrodes. This advantage was more apparent at low frequency where the capacitive reactance was more prominent. The capacitive reactance is inversely proportional to the frequency and capacitance. At 1 Hz, The impedance of 0.05 C/cm2 films were an order of a magnitude lower that of platinum. The
magnitude was further reduced by increasing the PEDOT thickness from the 0.05 to 0.5 C cm2 films. No significant difference was observed between the films produced from 0.5 and 1 C cm2 of deposition charge. Among the films deposited with the same amount of charge, ClO4 films, shown as blue lines, exhibited the lowest impedance followed by pTS (red lines) and PSS (black lines). The smaller phase angles plotted in Fig. 7b indicate that the reduced impedance was the result of high capacitance. 3.4. Biological performance: PC12 cell attachment and neurite outgrowth Fig. 8 shows typical micrographs demonstrating neurite extension on PEDOT samples at 96 h post plating. The number and length of neurites and number of PC12 cell bodies are presented in the box and whisker plots shown in Fig. 9. Thin pTS and PSS films, deposited with 0.05 or 0.1 C cm2, showed significantly more
Please cite this article in press as: Baek S et al. The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications. Acta Biomater (2014), http://dx.doi.org/10.1016/j.actbio.2014.04.004
8
S. Baek et al. / Acta Biomaterialia xxx (2014) xxx–xxx
C/cm2
PEDOT/pTS
PEDOT/ClO4
PEDOT/PSS
0.05
0.1
0.5
1
Platinum
Fig. 8. Neurite growth in PC12 cells on PEDOT substrates.
neurite growth than other films. However, the numbers of neurites on pTS and PSS films diminished rapidly from the 0.1 C cm2 films to the 0.5 C cm2 films. At 0.5 C cm2, there were more neurites on ClO4 films than on pTS films. Thicker films made with a charge >0.5 C cm2 did not provide biological benefits over conventional platinum electrodes. All thin films made with a charge
Contents lists available at ScienceDirect
Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat
The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications Sungchul Baek, Rylie A. Green ⇑, Laura A. Poole-Warren Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
a r t i c l e
i n f o
Article history: Received 21 January 2014 Received in revised form 26 March 2014 Accepted 2 April 2014 Available online xxxx Keywords: Conducting polymer PEDOT Dopant choice Topography Thickness
a b s t r a c t Poly(3,4-ethylenedioxythiophene) (PEDOT) films have attracted substantial interest as coatings for platinum neuroprosthetic electrodes due to their excellent chemical stability and electrical properties. This study systematically examined PEDOT coatings formed with different amounts of charge and dopant ions, and investigated the combination of surface characteristics that were optimal for neural cell interactions. PEDOT samples were fabricated by varying the electrodeposition charge from 0.05 to 1 C cm2. Samples were doped with either poly(styrenesulfonate), tosylate (pTS) or perchlorate. Scanning electron micrographs revealed that both thickness and nodularity increased as the charge used to produce the sample was increased, and larger dopants produced smoother films across all thicknesses. X-ray photoelectron spectroscopy confirmed that the amount of charge directly corresponded to the thickness and amount of dopant in the samples. Additionally, with increased thickness and nodularity, the electrochemical properties of all PEDOT coatings improved. However, neural cell adhesion and outgrowth assays revealed that there is a direct biological tradeoff related to the thickness and nodularity. Cell attachment, growth and differentiation was poorer on the thicker, rougher samples, but thin, less nodular PEDOT films exhibited significant improvements over bare platinum. PEDOT/pTS fabricated with a charge density of 165 eV, is summarized in Table 2. pTS and ClO4 films showed a doping ratio of 0.3–0.4 dopants per monomer. The doping ratio of PSS films was 0.6–0.7. The high doping ratio is likely due to the polymeric nature of PSS. The amount of dopant in 0.05 C cm2 ClO4, pTS or PSS was 3, 4 or 12 lg, respectively, and the amount in 1 C cm2 was 82, 102, 233 lg, respectively. 3.3. Electrical performance
Fig. 6. Changes in charge storage capacity over 800 cycles.
fabrication parameter, and by the doping ion, a constituent. While there was a general observation that higher charge density resulted in bigger nodules, the overall morphology of films, especially the 1 C cm2 films, was largely influenced by the choice of dopant. At all thicknesses, PEDOT/PSS films were smoother than films doped with ClO4 or pTS. Thick PEDOT/ClO4 films exhibited nodular morphology with an average nodule diameter of 40 lm. This unique morphology is well illustrated in Fig. 2d. The 1 C cm2 PEDOT/pTS film was comprised of smaller nodules, with an average diameter of 15 lm, randomly stacked together to form a rough and irregular microstructure. Fig. 3 shows a plot comparing the thicknesses measured from cross-sectional SEM, and theoretically calculated from XPS data.
3.3.1. Charge storage capacity and electrochemical stability CPs are pseudo-capacitors that allow concurrent resistive and capacitive charge transfer. In CV, purely capacitive and resistive charge transfer mechanisms are respectively indicated by square and linear curves. The cyclic voltammograms of PEDOT films, shown in Fig. 5, were generally trapezoids, representing the combined geometry of a linear and a square waveform. One exception was PEDOT/PSS films deposited with 1 C cm2 of charge. Instead of trapezoids exhibited in other samples, thick PEDOT/PSS films showed concave curves in a negative voltage range and a distinctive oxidation peak at 50 mV and a reduction pair at 151 mV. The size and percentage loss of CSC, which respectively indicates the electrochemical performance and stability, is depicted and tabulated in Fig. 6 and Table 3. There were two general trends observed regarding the electrochemical performance of PEDOT films. Firstly, films formed with higher charge density had higher CSC. Secondly, with the exception of the 0.05 C cm2 films that had similar CSC values regardless of dopant, the CSC of a film increased in order of decreasing dopant size from PSS, pTS to ClO4. The initial CSC of 1 C cm12 ClO4 film, 150.47 ± 6.29 mC cm2,
Table 3 The initial and the final charge storage capacity (CPC) of films and corresponding loss in CSC during 800 cycles. Charge (C/cm2)
Film
Initial CSC (mC cm2)
Final CSC (mC cm2)
CSC loss (%)
1
ClO4 pTS PSS
150.47 (±6.29) 135.43 (±7.16) 100.04 (±4.30)
91.88 (±5.08) 86.71 (±3.90) 68.23 (±4.33)
38.9 ± 4.2 36.0 ± 4.4 31.7 ± 4.5
0.5
ClO4 pTS PSS
90.66 (±2.54) 81.49 (±1.37) 67.78 (±1.59)
53.34 (±1.92) 48.91 (±1.78) 46.35 (±1.03)
41.2 ± 2.7 40.0 ± 2.41 31.6 ± 2.21
0.1
ClO4 pTS PSS
21.71 (±0.39) 21.37 (±0.71) 18.62 (±1.01)
16.59 (±0.49) 15.83 (±0.38) 14.93 (±0.6)
23.6 ± 2.7 25.9 ± 3.0 19.8 ± 5.4
0.05
ClO4 pTS PSS
10.50 (±0.70) 10.43 (±0.76) 10.52 (±0.63)
7.34 (±0.45) 7.1 (±0.88) 7.84 (±0.37)
30.1 ± 6.3 31.9 ± 9.8 25.5 ± 5.7
–
Pt
1.89 (±0.43)
2.28 (±0.15)
–
Please cite this article in press as: Baek S et al. The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications. Acta Biomater (2014), http://dx.doi.org/10.1016/j.actbio.2014.04.004
S. Baek et al. / Acta Biomaterialia xxx (2014) xxx–xxx
7
Fig. 7. (a) Electrical impedance and (b) corresponding phase angle of films having different thicknesses.
was 15 times higher than that of the 0.05 C cm2, and >75 times higher than that of platinum, 1.89 ± 0.43 mC cm2. It can be seen in Fig. 6 that the CSC of the 1 C cm2 PSS film is significantly less than the CSC of the other 1 C cm2 films. This was the direct result of the non-trapezoidal cyclic voltammograms, which significantly reduced the CSC in the negative voltage range. 3.3.2. Electrochemical impedance Fig. 7a and b show the electrical impedance and corresponding phase angle measured at frequencies ranging from 1 Hz to 10 kHz. The electrical impedance was shown to decrease with increasing thickness. All CPs presented significant electrochemical advantage over platinum electrodes. This advantage was more apparent at low frequency where the capacitive reactance was more prominent. The capacitive reactance is inversely proportional to the frequency and capacitance. At 1 Hz, The impedance of 0.05 C/cm2 films were an order of a magnitude lower that of platinum. The
magnitude was further reduced by increasing the PEDOT thickness from the 0.05 to 0.5 C cm2 films. No significant difference was observed between the films produced from 0.5 and 1 C cm2 of deposition charge. Among the films deposited with the same amount of charge, ClO4 films, shown as blue lines, exhibited the lowest impedance followed by pTS (red lines) and PSS (black lines). The smaller phase angles plotted in Fig. 7b indicate that the reduced impedance was the result of high capacitance. 3.4. Biological performance: PC12 cell attachment and neurite outgrowth Fig. 8 shows typical micrographs demonstrating neurite extension on PEDOT samples at 96 h post plating. The number and length of neurites and number of PC12 cell bodies are presented in the box and whisker plots shown in Fig. 9. Thin pTS and PSS films, deposited with 0.05 or 0.1 C cm2, showed significantly more
Please cite this article in press as: Baek S et al. The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications. Acta Biomater (2014), http://dx.doi.org/10.1016/j.actbio.2014.04.004
8
S. Baek et al. / Acta Biomaterialia xxx (2014) xxx–xxx
C/cm2
PEDOT/pTS
PEDOT/ClO4
PEDOT/PSS
0.05
0.1
0.5
1
Platinum
Fig. 8. Neurite growth in PC12 cells on PEDOT substrates.
neurite growth than other films. However, the numbers of neurites on pTS and PSS films diminished rapidly from the 0.1 C cm2 films to the 0.5 C cm2 films. At 0.5 C cm2, there were more neurites on ClO4 films than on pTS films. Thicker films made with a charge >0.5 C cm2 did not provide biological benefits over conventional platinum electrodes. All thin films made with a charge
