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Using white noise to gate organic transistors for dynamic monitoring of cultured cell layers.

Rivnay J, Leleux P, Hama A, Ramuz M, Huerta M, Malliaras GG, Owens RM - Sci Rep (2015)

Bottom Line: These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening.By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers.We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioelectronics, Ecole Nationale Superieure des Mines, CMP-EMSE, MOC, 13541 Gardanne, France.

ABSTRACT
Impedance sensing of biological systems allows for monitoring of cell and tissue properties, including cell-substrate attachment, layer confluence, and the "tightness" of an epithelial tissue. These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening. Organic transistors based on conducting polymers offer a promising route to efficiently transduce ionic currents to attain high quality impedance spectra, but collection of complete impedance spectra can be time consuming (minutes). By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers. We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

No MeSH data available.


Noise-based impedance sensing with OECTs.a. Wiring diagram of an OECT for noise based sensing. VD = −0.6 V, applied VG is uniform white noise of amplitude 100 mV, IG and ID can be measured individually or simultaneously. b. Raw noise recording of applied white noise, VG (black), as well as the measured current noise (ID, green; IG, blue) with cells (light colors) and without (dark colors). The FFT of 2 min noise recordings for the ID based measurements (c.) yielding the transconductance vs. frequency response of the ionic circuit, and of the IG based measurements (d.), providing an estimate of the system impedance. Dotted yellow lines are measurements of the same systems through a harmonic frequency sweeping approach. The grey region in (d.) is dominated by ambient current noise, rendering data in this region useless for impedance sensing using the gate current.
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f1: Noise-based impedance sensing with OECTs.a. Wiring diagram of an OECT for noise based sensing. VD = −0.6 V, applied VG is uniform white noise of amplitude 100 mV, IG and ID can be measured individually or simultaneously. b. Raw noise recording of applied white noise, VG (black), as well as the measured current noise (ID, green; IG, blue) with cells (light colors) and without (dark colors). The FFT of 2 min noise recordings for the ID based measurements (c.) yielding the transconductance vs. frequency response of the ionic circuit, and of the IG based measurements (d.), providing an estimate of the system impedance. Dotted yellow lines are measurements of the same systems through a harmonic frequency sweeping approach. The grey region in (d.) is dominated by ambient current noise, rendering data in this region useless for impedance sensing using the gate current.

Mentions: The OECT is wired as shown in Fig. 1a, measuring both drain and gate current simultaneously, with VD = −0.6 V [Ref. 20]. The geometry (50 × 50 μm2, ~130 nm thick) of the OECT is selected such that the maximum transconductance (gm = ∂ID/∂VG) is attained at VG = 0 V, so that the applied gate noise requires no offset, and excessive biasing across the cell monolayer can be minimized23. A Ag/AgCl gate electrode is immersed in cell culture media, the electrolyte in this case, and uniform white noise of 100 mV amplitude is applied while the resulting current noise is measured (Fig. 1b). The data analysis relies on the fast Fourier transform (FFT) of the resulting signals; shown in Fig. 1c,d as the FFT of a 2 min recording, smoothed over 50 pts. The measurement of the applied white noise confirms the uniform contributions of signal at all frequencies in the 1 Hz–20 kHz range. The ratios of the absolute value of the measured current and voltage FFTs provide the frequency dependent transconductance, gm = /FFT(ID,noise)///FFT(VG,noise)/, and impedance, /Z/ = /FFT(VG,noise)///FFT(IG,noise)/. The shape and magnitude of the transconductance and impedance are in good agreement with results from a frequency scan experiment. In the latter case, a sinusoidal signal is applied at the gate, and the ratios of the input and output sine wave amplitudes yield the dotted yellow traces in Fig. 1. The deviation in /Z/ of the noise results from the harmonic results at low frequencies is attributed to ambient noise in the measurement of low frequency gate current. The applied noise amplitude is selected carefully to minimize the exposure of excessive bias to the cells, but also to allow for proper recording of resulting device currents above the ambient background noise. An example of the transconductance dependence on VG noise amplitude is shown in Supplementary Figure S1, where the drain current is almost entirely dominated by ambient noise when the applied noise is <~1 mV. These results suggest lower applied bias can be utilized for a more restricted frequency range, in environments with lower ambient noise, or with a transistor of higher transconductance. The effect of shorter duration recordings is also included as a reference (Supplementary Figure S2); as expected, the minimum duration of a noise recording depends on the frequency range of interest.


Using white noise to gate organic transistors for dynamic monitoring of cultured cell layers.

Rivnay J, Leleux P, Hama A, Ramuz M, Huerta M, Malliaras GG, Owens RM - Sci Rep (2015)

Noise-based impedance sensing with OECTs.a. Wiring diagram of an OECT for noise based sensing. VD = −0.6 V, applied VG is uniform white noise of amplitude 100 mV, IG and ID can be measured individually or simultaneously. b. Raw noise recording of applied white noise, VG (black), as well as the measured current noise (ID, green; IG, blue) with cells (light colors) and without (dark colors). The FFT of 2 min noise recordings for the ID based measurements (c.) yielding the transconductance vs. frequency response of the ionic circuit, and of the IG based measurements (d.), providing an estimate of the system impedance. Dotted yellow lines are measurements of the same systems through a harmonic frequency sweeping approach. The grey region in (d.) is dominated by ambient current noise, rendering data in this region useless for impedance sensing using the gate current.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481393&req=5

f1: Noise-based impedance sensing with OECTs.a. Wiring diagram of an OECT for noise based sensing. VD = −0.6 V, applied VG is uniform white noise of amplitude 100 mV, IG and ID can be measured individually or simultaneously. b. Raw noise recording of applied white noise, VG (black), as well as the measured current noise (ID, green; IG, blue) with cells (light colors) and without (dark colors). The FFT of 2 min noise recordings for the ID based measurements (c.) yielding the transconductance vs. frequency response of the ionic circuit, and of the IG based measurements (d.), providing an estimate of the system impedance. Dotted yellow lines are measurements of the same systems through a harmonic frequency sweeping approach. The grey region in (d.) is dominated by ambient current noise, rendering data in this region useless for impedance sensing using the gate current.
Mentions: The OECT is wired as shown in Fig. 1a, measuring both drain and gate current simultaneously, with VD = −0.6 V [Ref. 20]. The geometry (50 × 50 μm2, ~130 nm thick) of the OECT is selected such that the maximum transconductance (gm = ∂ID/∂VG) is attained at VG = 0 V, so that the applied gate noise requires no offset, and excessive biasing across the cell monolayer can be minimized23. A Ag/AgCl gate electrode is immersed in cell culture media, the electrolyte in this case, and uniform white noise of 100 mV amplitude is applied while the resulting current noise is measured (Fig. 1b). The data analysis relies on the fast Fourier transform (FFT) of the resulting signals; shown in Fig. 1c,d as the FFT of a 2 min recording, smoothed over 50 pts. The measurement of the applied white noise confirms the uniform contributions of signal at all frequencies in the 1 Hz–20 kHz range. The ratios of the absolute value of the measured current and voltage FFTs provide the frequency dependent transconductance, gm = /FFT(ID,noise)///FFT(VG,noise)/, and impedance, /Z/ = /FFT(VG,noise)///FFT(IG,noise)/. The shape and magnitude of the transconductance and impedance are in good agreement with results from a frequency scan experiment. In the latter case, a sinusoidal signal is applied at the gate, and the ratios of the input and output sine wave amplitudes yield the dotted yellow traces in Fig. 1. The deviation in /Z/ of the noise results from the harmonic results at low frequencies is attributed to ambient noise in the measurement of low frequency gate current. The applied noise amplitude is selected carefully to minimize the exposure of excessive bias to the cells, but also to allow for proper recording of resulting device currents above the ambient background noise. An example of the transconductance dependence on VG noise amplitude is shown in Supplementary Figure S1, where the drain current is almost entirely dominated by ambient noise when the applied noise is <~1 mV. These results suggest lower applied bias can be utilized for a more restricted frequency range, in environments with lower ambient noise, or with a transistor of higher transconductance. The effect of shorter duration recordings is also included as a reference (Supplementary Figure S2); as expected, the minimum duration of a noise recording depends on the frequency range of interest.

Bottom Line: These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening.By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers.We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioelectronics, Ecole Nationale Superieure des Mines, CMP-EMSE, MOC, 13541 Gardanne, France.

ABSTRACT
Impedance sensing of biological systems allows for monitoring of cell and tissue properties, including cell-substrate attachment, layer confluence, and the "tightness" of an epithelial tissue. These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening. Organic transistors based on conducting polymers offer a promising route to efficiently transduce ionic currents to attain high quality impedance spectra, but collection of complete impedance spectra can be time consuming (minutes). By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers. We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

No MeSH data available.