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Design of a microscopic electrical impedance tomography system for 3D continuous non-destructive monitoring of tissue culture.

Lee EJ, Wi H, McEwan AL, Farooq A, Sohal H, Woo EJ, Seo JK, Oh TI - Biomed Eng Online (2014)

Bottom Line: We developed a new micro-EIT system and report on simulation and experimental results of its macroscopic model.From numerical and experimental results, we estimate that at least 20 × 40 electrodes with 120 μm spacing are required to monitor the complex shape of ingrowth neotissue inside a scaffold with 300 μm pore.Future challenges include manufacturing a bioreactor-compatible container with a dense array of electrodes and a larger number of measurement channels that are sensitive to the reduced voltage gradients expected at a smaller scale.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Impedance Imaging Research Center, Kyung Hee University, 46-701 Yongin, Korea. tioh@khu.ac.kr.

ABSTRACT

Background: Non-destructive continuous monitoring of regenerative tissue is required throughout the entire period of in vitro tissue culture. Microscopic electrical impedance tomography (micro-EIT) has the potential to monitor the physiological state of tissues by forming three-dimensional images of impedance changes in a non-destructive and label-free manner. We developed a new micro-EIT system and report on simulation and experimental results of its macroscopic model.

Methods: We propose a new micro-EIT system design using a cuboid sample container with separate current-driving and voltage sensing electrodes. The top is open for sample manipulations. We used nine gold-coated solid electrodes on each of two opposing sides of the container to produce multiple linearly independent internal current density distributions. The 360 voltage sensing electrodes were placed on the other sides and base to measure induced voltages. Instead of using an inverse solver with the least squares method, we used a projected image reconstruction algorithm based on a logarithm formulation to produce projected images. We intended to improve the quality and spatial resolution of the images by increasing the number of voltage measurements subject to a few injected current patterns. We evaluated the performance of the micro-EIT system with a macroscopic physical phantom.

Results: The signal-to-noise ratio of the developed micro-EIT system was 66 dB. Crosstalk was in the range of -110.8 to -90.04 dB. Three-dimensional images with consistent quality were reconstructed from physical phantom data over the entire domain. From numerical and experimental results, we estimate that at least 20 × 40 electrodes with 120 μm spacing are required to monitor the complex shape of ingrowth neotissue inside a scaffold with 300 μm pore.

Conclusion: The experimental results showed that the new micro-EIT system with a reduced set of injection current patterns and a large number of voltage sensing electrodes can be potentially used for tissue culture monitoring. Numerical simulations demonstrated that the spatial resolution could be improved to the scale required for tissue culture monitoring. Future challenges include manufacturing a bioreactor-compatible container with a dense array of electrodes and a larger number of measurement channels that are sensitive to the reduced voltage gradients expected at a smaller scale.

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Sample container and current driving electrodes for producing linearly independent current patterns.(a) The sample container includes the 9 gold coated electrodes used for injecting source and sink currents on the side walls. The 360 voltage sensing electrodes are located on the imaging plane 1, 2, and 3. (b) Detailed design and dimensions of the current driving electrodes.
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Fig3: Sample container and current driving electrodes for producing linearly independent current patterns.(a) The sample container includes the 9 gold coated electrodes used for injecting source and sink currents on the side walls. The 360 voltage sensing electrodes are located on the imaging plane 1, 2, and 3. (b) Detailed design and dimensions of the current driving electrodes.

Mentions: Figure 3 shows the sample container and the design of the current driving electrodes. As explained in the previous section, we needed to control the direction of injection current by the selection of the current driving electrode pairs. This required independent connection of current outputs to current driving electrodes. In the analog backplane, we used low-voltage, T-switches (MAX4529, Maxim, USA) to construct a ‘T’ configuration for handling rail-to-rail signals in either direction. The 360 voltage sensing electrodes on three imaging planes in Figure 1(b) were considered to be a single 24 × 15 electrode array. There are 15 electrodes in each row with a total of 24 rows equally placed in three sides of the container. The first voltmeter measures the differential voltage between electrode 1 and 2 in the same row. From the second voltmeter to the 14th voltmeter, they measure the differential voltage between two adjacent electrodes in a row in the same manner. The 15th voltmeter measures the voltage from electrode channel 15 with reference to the circuit ground. There is an additional measurement circuit used for measuring the amount of applied current inside the current source via a current sensing resistor. Each differential recording channel included a variable gain amplifier. The performance characteristics were measured in terms of crosstalk, amplitude stability error (ASE), total harmonic distortion (THD), and signal to noise ratio (SNR) to evaluate the proposed method. The ASE is measured as the standard deviation divided by the mean of the output current amplitude recorded over 1 h. The THD was computed by 5 using 9 harmonic components. The SNR is defined as the ratio of the mean to standard deviation of the repeated measurements. Figure 3


Design of a microscopic electrical impedance tomography system for 3D continuous non-destructive monitoring of tissue culture.

Lee EJ, Wi H, McEwan AL, Farooq A, Sohal H, Woo EJ, Seo JK, Oh TI - Biomed Eng Online (2014)

Sample container and current driving electrodes for producing linearly independent current patterns.(a) The sample container includes the 9 gold coated electrodes used for injecting source and sink currents on the side walls. The 360 voltage sensing electrodes are located on the imaging plane 1, 2, and 3. (b) Detailed design and dimensions of the current driving electrodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4196084&req=5

Fig3: Sample container and current driving electrodes for producing linearly independent current patterns.(a) The sample container includes the 9 gold coated electrodes used for injecting source and sink currents on the side walls. The 360 voltage sensing electrodes are located on the imaging plane 1, 2, and 3. (b) Detailed design and dimensions of the current driving electrodes.
Mentions: Figure 3 shows the sample container and the design of the current driving electrodes. As explained in the previous section, we needed to control the direction of injection current by the selection of the current driving electrode pairs. This required independent connection of current outputs to current driving electrodes. In the analog backplane, we used low-voltage, T-switches (MAX4529, Maxim, USA) to construct a ‘T’ configuration for handling rail-to-rail signals in either direction. The 360 voltage sensing electrodes on three imaging planes in Figure 1(b) were considered to be a single 24 × 15 electrode array. There are 15 electrodes in each row with a total of 24 rows equally placed in three sides of the container. The first voltmeter measures the differential voltage between electrode 1 and 2 in the same row. From the second voltmeter to the 14th voltmeter, they measure the differential voltage between two adjacent electrodes in a row in the same manner. The 15th voltmeter measures the voltage from electrode channel 15 with reference to the circuit ground. There is an additional measurement circuit used for measuring the amount of applied current inside the current source via a current sensing resistor. Each differential recording channel included a variable gain amplifier. The performance characteristics were measured in terms of crosstalk, amplitude stability error (ASE), total harmonic distortion (THD), and signal to noise ratio (SNR) to evaluate the proposed method. The ASE is measured as the standard deviation divided by the mean of the output current amplitude recorded over 1 h. The THD was computed by 5 using 9 harmonic components. The SNR is defined as the ratio of the mean to standard deviation of the repeated measurements. Figure 3

Bottom Line: We developed a new micro-EIT system and report on simulation and experimental results of its macroscopic model.From numerical and experimental results, we estimate that at least 20 × 40 electrodes with 120 μm spacing are required to monitor the complex shape of ingrowth neotissue inside a scaffold with 300 μm pore.Future challenges include manufacturing a bioreactor-compatible container with a dense array of electrodes and a larger number of measurement channels that are sensitive to the reduced voltage gradients expected at a smaller scale.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Impedance Imaging Research Center, Kyung Hee University, 46-701 Yongin, Korea. tioh@khu.ac.kr.

ABSTRACT

Background: Non-destructive continuous monitoring of regenerative tissue is required throughout the entire period of in vitro tissue culture. Microscopic electrical impedance tomography (micro-EIT) has the potential to monitor the physiological state of tissues by forming three-dimensional images of impedance changes in a non-destructive and label-free manner. We developed a new micro-EIT system and report on simulation and experimental results of its macroscopic model.

Methods: We propose a new micro-EIT system design using a cuboid sample container with separate current-driving and voltage sensing electrodes. The top is open for sample manipulations. We used nine gold-coated solid electrodes on each of two opposing sides of the container to produce multiple linearly independent internal current density distributions. The 360 voltage sensing electrodes were placed on the other sides and base to measure induced voltages. Instead of using an inverse solver with the least squares method, we used a projected image reconstruction algorithm based on a logarithm formulation to produce projected images. We intended to improve the quality and spatial resolution of the images by increasing the number of voltage measurements subject to a few injected current patterns. We evaluated the performance of the micro-EIT system with a macroscopic physical phantom.

Results: The signal-to-noise ratio of the developed micro-EIT system was 66 dB. Crosstalk was in the range of -110.8 to -90.04 dB. Three-dimensional images with consistent quality were reconstructed from physical phantom data over the entire domain. From numerical and experimental results, we estimate that at least 20 × 40 electrodes with 120 μm spacing are required to monitor the complex shape of ingrowth neotissue inside a scaffold with 300 μm pore.

Conclusion: The experimental results showed that the new micro-EIT system with a reduced set of injection current patterns and a large number of voltage sensing electrodes can be potentially used for tissue culture monitoring. Numerical simulations demonstrated that the spatial resolution could be improved to the scale required for tissue culture monitoring. Future challenges include manufacturing a bioreactor-compatible container with a dense array of electrodes and a larger number of measurement channels that are sensitive to the reduced voltage gradients expected at a smaller scale.

Show MeSH
Related in: MedlinePlus