HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials and Instruments
2.1.1. Hydraulic Unit
2.1.2. Electric Unit
2.1.3. Control Unit
2.2. Target-Holder Architecture
2.3. Temperature Measurements
2.4. Cell Line and Cell Culture
2.5. Validation of HyCHEED
2.5.1. Choice and Evaluation of Pulse Settings and Target Temperatures
- a significant temperature difference compared to 37 °C, allowing us to demonstrate the capability of HyCHEED to operate at different temperatures;
2.5.2. Operation Protocol of HyCHEED
2.6. Evaluation of In Vitro Experiments Using HyCHEED
2.6.1. Establishing the Electrical Specific Conductivity of the Target Volume
2.6.2. Cell Viability Assays/Reagents
2.6.3. Statistical Analyses
3. Results
3.1. Validation of HyCHEED
3.1.1. Read-Outs of Electrical Parameters
3.1.2. Temperature Measurements
3.2. Effects of Thermally Controlled Irreversible Permeabilization on the Electrical Specific Conductivity and Cell Viability
3.2.1. Electrical Specific Conductivity
- Temperature only:
- In Figure 7B, the σav ratio for the control at 46 °C increased by 1.2-fold with respect to the control at 37 °C.
- Electric-field strength only; during the pulse in the presence of the electric field (focus on Figure 7A):
- In Figure 7A, the σav ratios for 1250 V·cm−1 at 37 °C and 46 °C increased by 2.5 and 2.9-folds, while the σav ratios for 500 V·cm−1 at 37 °C and 46 °C increased by 2.0 and 2.4-folds.
- Electric-field strength only; post-treatment in the absence of the electric field (focus on Figure 7B):
- In Figure 7B, the σav ratios for 1250 V·cm−1 at 37 °C and 46 °C increased by 1.2 and 2.1-folds, while the σav ratios for 500 V·cm−1 at 37 °C and 46 °C increased by 1.1 and 1.6-folds.
- In Figure 7B, the σav ratio for the control at 46 °C increased by 1.2-fold, while in the σav ratios for 500 V·cm−1 and 1250 V·cm−1 at 46 °C increased by 1.6 and 2.1-fold.
- Presence of electric field during the treatment:
- Combined effects of electric-field strength and temperature; during the 90th pulse in the presence of the electric field (focus on Figure 7A):
- In Figure 7A, the σav ratios for 500 V·cm−1 and 1250 V·cm−1 during the 90th pulse at 46 °C increased by 2.4 and 2.9-folds, while the σav ratios for the same pulse parameters at 37 °C increased by 2.0 and 2.5-folds.
- Combined effects of electric-field strength and temperature; post-treatment in the absence of the electric field (focus on Figure 7B):
- In Figure 7B, the σav ratios for 500 V·cm−1 and 1250 V·cm−1 post-treatment at 46 °C increased by 1.2 and 2.1-folds, while the σav ratios for the same pulse parameters at 37 °C increased by 1.1 and 1.6-folds.
3.2.2. Cell Viability
4. Discussion
4.1. Main Research Objective: HyCHEED Was Validated
4.2. Secondary Research Objective: Irreversible Electroporation Characteristics Are Influenced by Electric-Field Strength and Temperature
4.3. HyCHEED Is Suitable for Investigation of Electroporation Treatment Modalities
4.4. HyCHEED Is Suitable for Investigation of Radio-Frequency Treatments
4.5. Future Directions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations and Definitions
Abbreviations and symbols of quantities | Unit | Definition |
C-container | Container with demineralized water intended to cool off a target volume. | |
Demi-water | Demineralized water. | |
IRE | Irreversible electroporation. | |
IPE | Irreversible permeabilization effect (we chose IPE instead of IRE effect to distinguish between only the permeabilization effect, and the permeabilization and the thermal effects jointly produced by IRE). | |
H-container | Container with demineralized water intended to heat a target volume. | |
HF-IRE | High-frequency irreversible electroporation. | |
HyCHEED | Hydraulically controllable heat exchange electroporation device. | |
NA | Not applicable. | |
Post-treatment σav | [S·m−1] | Average electrical specific conductivity of a target volume that is measured after the treatment. |
T-holder | Target holder. | |
TV | Target volume. | |
E | [V·m−1] or [V·cm−1] | Electric-field vector. |
J | [A·m−2] | Electric-current density. |
J · E | [W·m−3] | The Joule Heating term; the heat generation rate per unit volume. |
cp | [J·kg−1·°C−1] | Specific heat capacity of a medium. |
d | [m] | Distance between electrode plates of an electroporation cuvette. |
fP | [Hz] | Pulse frequency. |
HV | [W·m−3·°C−1] | Volumetric heat transfer coefficient between the target volume and its direct ambiance. |
t | [s] or [min] | Time. |
t0, t1, …, t5 | [min] | Time points. |
tinit | [s] | Initial time at which irreversible electroporation treatment starts. |
tP | [s] | Pulse duration. |
σ | [S·m−1] | Electrical specific conductivity of a target volume. |
σav | [S·m−1] | Average electrical specific conductivity of a target volume. |
A | [m2] | Surface of a target volume that is contacting the electrode plate of an electroporation cuvette. |
E = |E | | [V·m−1] or [V·cm−1] | Magnitude of an electric-field vector. |
EIRE(th) | [V·m−1] | Electric-field threshold of irreversible electroporation; minimum electric-field value that ablates target cells/tissue during the irreversible electroporation. |
I | [A] | Measured electric current. |
SD | Standard deviation. | |
T | [°C] | Temperature. |
Ttarget | [°C] | Target temperature. |
TA | [°C] | Temperature of the direct ambient of the target volume. |
Tav | [°C] | Average temperature evolution over time. |
Φ | [V] | Measured voltage. |
Appendix A—Mathematical Description of Stable Temperature Control in Treated Volume
- Pretreatment (E = 0 V·m−1), HyCHEED has to heat the TV up to Ttarget. This implies that at t = 0 s the temperature of the TV is lower than TA, and in time the temperature must reach Ttarget. Therefore, TA = Ttarget. See Figure 1A.
- During the treatment (E > 0 V·m−1), a stable temperature is maintained when the temperature rise caused purely by the electric pulses (Figure 1B) is combined with the temperature decrease caused solely by the cooling effect of term HV · (T − TA) (Figure 1C) to obtain a steady temperature as in Figure 1D. To satisfy this condition, TA must be adjusted at t = tinit such that TA < Ttarget. Using the combination of Equations (A1) and (A3), we can calculate TA by reducing Equation (A1) into
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Ttarget [°C] | Temperature of H-Container [°C] | Temperature of C-Container [°C] |
---|---|---|
37 | 37.5 | 32.4 |
46 | 46.1 | 44.2 |
Ttarget [°C] | E [V·cm−1] | |
---|---|---|
500 | 1250 | |
37 | 36.75 ± 0.58 | 36.86 ± 0.34 |
46 | 46.44 ± 0.82 | 46.66 ± 0.70 |
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Agnass, P.; Rodermond, H.M.; Zweije, R.; Sijbrands, J.; Vogel, J.A.; van Lienden, K.P.; van Gulik, T.M.; van Veldhuisen, E.; Franken, N.A.P.; Oei, A.L.; et al. HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings. Sensors 2020, 20, 6227. https://doi.org/10.3390/s20216227
Agnass P, Rodermond HM, Zweije R, Sijbrands J, Vogel JA, van Lienden KP, van Gulik TM, van Veldhuisen E, Franken NAP, Oei AL, et al. HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings. Sensors. 2020; 20(21):6227. https://doi.org/10.3390/s20216227
Chicago/Turabian StyleAgnass, Pierre, Hans M. Rodermond, Remko Zweije, Jan Sijbrands, Jantien A. Vogel, Krijn P. van Lienden, Thomas M. van Gulik, Eran van Veldhuisen, Nicolaas A. P. Franken, Arlene L. Oei, and et al. 2020. "HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings" Sensors 20, no. 21: 6227. https://doi.org/10.3390/s20216227
APA StyleAgnass, P., Rodermond, H. M., Zweije, R., Sijbrands, J., Vogel, J. A., van Lienden, K. P., van Gulik, T. M., van Veldhuisen, E., Franken, N. A. P., Oei, A. L., Kok, H. P., Besselink, M. G., & Crezee, J. (2020). HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings. Sensors, 20(21), 6227. https://doi.org/10.3390/s20216227