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Journal of Information Technology and Applications Vol. 7, No. 2, pp. 30-33 2013 Cell Membrane of Biologic Cells for Gate Dielectric Application I. J. Hsieh Department of Electrical Engineering, Chung-Hua University, Hsinchu, Taiwan, R.O.C. E-mail: [email protected] Abstract In the future, according to the continuous scaling down of device, the thickness of gate oxide has to be reduced. The thickness of gate oxide will be decreased to the limitation. It has been investigated into the feasibility of the biological cell, in order to substitute for the gate dielectric. Then it is experimented with the relationship between the cell and the electric field. Keywords: gate oxide, biological cell, and dielectric * Corresponding author. 30 Journal of Information Technology and Applications Vol. 7, No. 2, pp. 30-33 2013 1. Introduction The CMOS technology is being continuously scaled towards smaller dimensions region due to the increasing need for higher speed, integration density, as well as lower power consumption applications [1-2]. The continuous scaling down of device, the thickness of gate oxide has to be reduced. The thickness of gate oxide will be decreased to the limitation. It is the purpose to investigate the feasibility of the biological cell, in order to substitute for the gate dielectric in this paper. The penetration of cell membrane is important for the cloning of Dolly sheep. One role played by the electric field used in cloning is to cause recoverable transient breakdown of cell membrane for both donor and recipient cells. However, there is only little understanding of cell membrane integrity dependence on electric field as shown in Fig.1 [3]. In addition, it is wondering if it is possible to control the transient breakdown in multi- parallel, which is important for certain applications like bio-computers. For these purposes, we have integrated the human placenta TL and lung cancer cell A549 into 3D trap arrays on Si substrate and studied the electrically stimulated cell membrane breakdown phenomenon. The applied electric field can break down the cell membrane and destroy the cell. The dependence of cell membrane breakdown distributions on electric field have been measured. From measured data, the survival rate of cells under the electric field stress is similar to the gate dielectric reliability of MOSFET as shown in Fig.2 [4]. Fig.2 The Cell membrane is similar to the gate dielectric in the MOSFET. 2. Experiments KOH was used to etch the 4-in Si wafer to a designed deep trench array structure after depositing 300 nm Si3N4 for masking. The average depth of the trench was 50 m , which was deep enough for locating and fixing the cells. Then a 200 nm SiO2 was grown for electrically isolating the low-resistivity Si substrate. Depositing 2 m thick aluminum layer and subsequent patterning fabricated the electrode. The human placenta TL and lung cancer cell A549 were directly cultured on the fabricated 3D traps by immerging the Si chip into the culture medium. The cell membrane breakdown was studied by applying voltage to the electrode pad of 3D traps. The survival rate was calculated by counting the Trypan blue stained cells, since the cell membrane was already broken under the applied electric field to allow the blue dye to diffuse into the cells. 3. Results and Discussions Since the cell membrane was made of lipids and proteins with relatively poor electrical conductivity as shown in Fig.3. It can be treated as a dielectric layer similar to gate dielectric used in Si MOSFET. Fig.4 shows the fabricated 3D trap arrays and metal lines on Si substrate for cell culture. Fig.5 reveals the current flowing through the cells under applied voltage. The cell membrane behaves like an insulator layer when the voltage is smaller than 3 V, since only small current was flowing through the cells and closed to dummy culture medium. However, the current density increased linearly with increasing voltage, as the voltage is larger than 5 V, indicating that some cell membranes were broken to release ions from cytoplasm and nucleus. Fig.1 The principle of the cell membrane is integrity dependence on the electric field. 31 Journal of Information Technology and Applications Vol. 7, No. 2, pp. 30-33 2013 (a) (b) (c) Fig.3 (a) The TEM picture of a human placenta cell, (b) the structure of a MOSFET, and (c) the TEM picture of the gate dielectric in the MOSFET. by using Trypan Blue stain, which stained the cell cytoplasm if there were leaks on the cell membrane. Fig.6 (a) and (b) show the comparison of human placenta TL cells before and after applied voltage, respectively, where the dyes only stain the cells if the membrane was damaged by electric field. Fig.4 The picture of the fabricated 3-D cell traps on Si with electrical electrode patterns. The trench is for allocating and restraining the cells. (a) (b) Fig.6 The pictures of the human placenta TL cells (a) before and (b) after Electric field applying, and stained by Typan Blue is applied to both case but only stains the cells after applying voltage because of the leaks on the cell membranes. By counting the number of the stained cells (broken cell membrane) and unstained cells, we analyzed the relationship between the applied electric field and the survival rate of the cells. Fig.7 shows the survival rate of human placenta cells after 20 sec electric stress. The survival rate started to decrease abruptly after increasing electric field > 40 V/cm and reached <4 % at 80 V/cm. The measured reducing survival rate trend of human placenta cells with increasing electric field was consistent with those of human lung cell A549 shown in Fig.8 shows the survival rate vs. distance between two electrodes for human lung cancer cell A549 after applied 0 ~ 20 V linearly sweep voltage. The survival rate reached a higher value of 97 % at the distance of 3000 μm but reduced to 74 % at 1000μm, which suggests that the electric field breakdown the cell membranes are similar to that of the gate dielectric in MOSFET. Fig.5 The current density flowing through the cells with the applied voltage. Some cell membrane started to breakdown and broken at above 4V. The dummy cultivation liquid keeps very low conductivity over the whole voltage range. At higher electric field, the cell membranes were completely broken and the nucleus was exposed as analyzed by transmission electric microscope (TEM). The status of the cell membrane could be investigated 32 Journal of Information Technology and Applications Vol. 7, No. 2, pp. 30-33 2013 [4] Fig.7 The survival rate of the human placental TL cells with the applied electric field. The survival rate reduces from ~100 % to < 4 % after 40 V/cm. Fig.8 The survival rate of the human lung cancer cells with the applied electric field. The reduction trend with increasing electric field is similar to that of the human placenta TL cells shown in Fig.6. 4. Conclusions The integration of cells into 3D trenched trap arrays in Si substrate and the electrical control of the cell membranes integrity are important for future biomedical applications. In order to substitute for the gate dielectric, the stability of the biological cell has been investigated. References [1] [2] [3] K. Rim, J. Welser, J. L. Hoyt and J. F. Gibbons, "Enhanced hole mobilities insurface-channel strained-Si p-MOSFETs," Electron Devices Meeting, pp. 517-520, (1995). K. Ismail, J. O. Chu and B. S. Meyerson, “High hole mobility in SiGe alloys for device applications,” Appl. Phys. Lett, 3124, (1994). J. A. Lundqvist, F. Sahlin, M. A. I. Å berg, A. Strömberg, P. S. Eriksson, and O.Orwar, “Altering the biochemical state of individual cultured cells and organelles with ultramicroelectrodes,” The National Academy of 33 Sciences , Vol.95, pp. 10356-10360 ,September (1998). H. M. Eppich, R. Foxall, K. Gaynor, D. Dombkowski, N. Miura, T. Cheng, S. S. Arrieta, R.H. Evans, J. A. Mangano, F. I. Preffer, and D. T. Scadden, “Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants”, Nature Bio-technology, Vol.18 Aug. (2000)