簡易檢索 / 詳目顯示

研究生: 張聖任
論文名稱: 應用於細胞膜外量測之CMOS微加工神經電晶體感測系統
CMOS-micromachined, Neuro-Transistor Microsystem for Extracellular Neural Recording
指導教授: 陳新
Chen, Hsin
口試委員: 盧向成
葉世榮
鍾文耀
蔡嘉明
陳新
學位類別: 博士
Doctor
系所名稱: 電機資訊學院 - 電子工程研究所
Institute of Electronics Engineering
論文出版年: 2012
畢業學年度: 101
語文別: 英文
論文頁數: 113
中文關鍵詞: 金氧半電晶體細胞膜外量測
外文關鍵詞: MOSFET, Extracellular neural recording
相關次數: 點閱:1下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 近年來,神經工程的研究,如腦機介面及腦傷輔具等逐漸受到重視,此方面知識技術的拓展有助於藥學、醫學上的進步,另一方面亦可增進人們對於腦的瞭解。甚至可幫助中風或腦傷的病人恢復部分的自主能力,而腦與機電儀器的介面,主要的功能為紀錄神經細胞活動時所產生的電訊號,或用電訊號刺激神經細胞。測量神經的電訊號的方法,又分為細胞膜內與膜外記錄兩種,相較於膜內紀錄,膜外記錄優點在於非侵入式記錄適合長時間以及同時記錄大批樣本測量,但缺點就是記錄到訊號較小,較容易受雜訊干擾。
    本論文試圖設計一種低雜訊且與標準CMOS製成相容的神經-矽介面並應用於細胞膜外訊號記錄。而記錄電路與感測器的整合更降低感測器陣列系統在於佈局上的複雜。感測介面是採用金屬氧化物半導體為基礎(MOSFET),並透過晶粒等級後製程加工為氧半電晶體(OSFET)。在實際的測量中發現氧半電晶體存在著一些不理想特性,包含著製程變異造成電性誤差、臨限電壓(Vth)的飄移以及後製程後電晶體雜訊的增加。因此在電路設計中,最後採用臨限電壓自動補償迴路克服製程變異以及臨限電壓飄移所造成陣列系統量測之不便。雜訊的增加,則發現為水溶液中離子被閘極氧化層表面缺陷捕抓所形成。
    論文中將詳細介紹後段製程加工、神經-矽介面特性分析、閘極(gate)與基底(bulk)偏壓對氧半電晶體雜訊的影響、電路設計考量,以及實際生物訊號測量結果。


    Recently, research on the neuroscience is becoming a potential subject and holds a lots attraction, such as Brain Machine Interface (BMI) or the Brain-Computer Interface (BCI). The development of neuroscience not only promotes the progress of the medicine and pharmacology but also the understanding of brain function. Furthermore, the neural prosthesis is useful for patients with neural diseases to restore part of their physiological functions. The bidirectional communication is based on recording neural activity and stimulating neurons. Intracellular recording and extracellular recording are both approaches to monitored neural activity. Compared with Intracellular recording, extracellular recording has the ability to record large amount of samples and the synchronized activities.
    This thesis proposes a low-noise, CMOS-compatible, neuro-silicon interface for extracellular recording. For the multi-channel array system, CMOS-compatible sensor can be integrated with the recording circuit to decrease the routing complexity. The interface is based on the OSFET, which is a MOSFET with several micromachined process steps. In the experimental results, we find that OSFETs have some unideal characteristics, process variation、threshold-voltage drift and increased noise after post process. Finally, the automatic Vth-compensation feedback loop is used to overcome the biasing complex for array system.
    The post-CMOS process, characteristics of neuro-silicon interface, the circuit design, the influence of gate to bulk voltage for OSFET noise,and the results of biological tests are introduced in the thesis.

    Abstract 摘要 致謝 Contents i List of Figures v List of Tables xii 1. Introduction 1 1.1 Motivation 1 1.2 Chapter Layout 2 2. Literature Review 5 2.1 Electrophysiology of Neurons 5 2.2 The Neuro-Electronic Interfaces 8 2.2.1 Conventional Electrophysiology Setup 8 2.2.2 Models of the Neuro-Electrode Interface 10 2.2.3 Planar Micro-Electrode Arrays 13 2.2.4 Planar Neuron-Transistor Arrays 16 2.3 Neural Recording Circuits 19 2.4 Noise Characteristics of Field-Effect Transistors 23 3. Characterization of Neuro-Transistors 25 3.1 The Fabrication of Oxide-Semiconductor, Field-effect Transistors(OSFETs) 25 3.1.1 The Structure Design 26 3.1.2 Post-Micromachining Processes 28 3.2 The 1st Neuro-Transistor Chip 31 3.3 Electric Characteristics of OSFETs 39 3.2.1 Comparison between MOSFETs and OSFETs …. 40 3.2.2 Threshold-Voltage Drift 42 3.2.3 Noise Characteristics of OSFETs 47 3.2.4 Noise Characteristics of Hybrid-Mode OSFETs 51 4. Design of Recording Circuits for Neuro-Transistors 53 4.1. Current-Mode Recording Circuit 53 4.1.1 Monolithically-Integrates Circuitry Design 53 4.1.2 Experimental Result and Discussion 54 4.2 The 2nd Neuro-Transistor Chip 58 4.3 Drift-Compensation Recording Circuit 60 4.3.1 Design Considerations and Circuit Architecture 60 4.3.1 Experimental Result and Discussion 64 4.4 Surface Modification with Si3N4 69 4.5 Summary 73 5. The Neuro-Transistor Microsystem 74 5.1 Design Considerations 74 5.2 The Improved Recording Circuit 75 5.2.1 Automatic Drift-Compensation Recording Circuit 75 5.2.2 Drift-Tolerable, Low-Noise Recording Circuit 79 5.3 Simulation Results 82 5.3.1 Simulation Result of Automatic Drift-Compensation Recording Circuit 82 5.3.2 Simulation result of Drift-tolerable, Low-Noise Recording Circuit 85 5.4 Chip Layout and Specifications 86 6. Experimental results of the Neuro-tranistor System 89 6.1 Electrical Tests 89 6.1.1 Testing Result of the Automatic Drift-Compensation Recording Circuit 90 6.1.2 Testing Result of the Drift-tolerable, Low-Noise Recording Circuit ……………………………….93 6.2 Biological Tests …………………………………… 102 6.3 Summary for Neuro-Transistor System …………… 104 7. Conclusion and Future work 106 7.1 Conclusion 106 7.2 Future work 107 Reference 108

    [1] B. He, Neural Engineering, 1st ed. Kluwer Academic, 2005.
    [2] ”Cell membrane” [online]. Available: mmdays.com/2007/11/10/action_potential/
    [3] S. References, A. Hodgkin, and A. Huxley, “A quantitative description of membrane current and its application to conduction and excitation in nerve,” J Physiol, vol.117, no. 4, pp. 500–544, 1952.
    [4] Eric R. Kandel, James Schwartz, and Thomas Jessell., Principles of Neural Science, 4th ed. McGraw-Hill, New York
    [5] Jenkner, M.; Tartagni, M.; Hierlemann, A.; Thewes, R. “cell based cmos sensor and actuator arrays” IEEE Journal of Solid-State Circuits, vol. 39, pp. 2431 – 2437, 2004.
    [6] F. Patolsky and et. al., “Detectioin, stimulation, and inhibition of neuronal signals with high density nanowire transistor arrays,” Science, vol. 313, pp. 1100 – 1104, 2006.
    [7] P. Fromherz and et al., “Membrane transistor with giant lipid vesicle touching a silicon chip,” APPLIED PHYSICS A-MATERIALS SCIENCE and PROCESSING, vol. 69, no. 5, pp. 571 – 576, 1999.
    [8] K. Wise and et. al., “Wireless implantable microsystems: High-density electronic interfaces to the nervous system,” Proceedings of the IEEE, vol. 92, no. 1, pp. 76–97, 2004.
    [9] M. Ho and et. al., “Cmos micromachined probes by die-level fabrication for extracellular neural recording,” Journal of MicroMech.and MicroEng., vol. 17, pp. 283–290, 2006.
    [10] R. Weis and P. Fromherz, “Frequency dependent signal transfer in neuron transistors,” Physical Review E, vol. 55, no. 1, pp. 877–889, 1997.
    [11] P. Fromherz, “Extracellular recording with transistors and the distribution of ionic conductances in a cell membrane,” European Biophysics Journal, vol.28, no.3, pp. 254–258, 1999.
    [12] A. Lambacher, M. Jenkner, M. Merz, B. Eversmann, R.A. Kaul, F. Hofmann, R. Thewes and P. Fromherz, “Electrical Imaging of Neuronal Activity by Multi-Transistor-Array (MTA) Recording at 7.8 µm Resolution” Applied Physics A, vol. 79 , pp 1607-1611, 2004
    [13] B. Eversmann and et. al., “A 128x128 cmos biosensor array for extracellular recording of neural activity,” IEEE Journal of Solid-State Circuits, vol. 38, no. 12, pp. 2306 – 2317,2003.
    [14] L. Berdondini, P. Van der Wal, O. Guenat, N. de Rooij, M. Koudelka-Hep, P. Seitz, R. Kaufmann, P. Metzler, N. Blanc, and S. Rohr, “High-density electrode array for imaging in-vitro electrophysiological activity,” Biosensors and Bioelectronics, vol. 21,pp. 167–174, 2005.
    [15] L. Berdondini, P. Massobrio, M. Chiappalone, M. Tedesco, K. Imfeld, A. Maccione, M. Gandolfo, M. Koudelka-Hep, and S. Martinoia, “Extracellular recordings from locally dense microelectrode arrays coupled to dissociated cortical cultures,” Journal of Neuroscience Methods, vol. 177, no. 2, pp. 386–396, 2009
    [16] P. Bergveld. “Thirty years of ISFETOLOGY: What happened in the past 30 years and what may happen in the next 30 years.” Sensors & Actuators: B. Chemical, 88(1):1-20, 2003.
    [17] D.S. Kim, Y.T. Jeong, H.J. Park, J.K. Shin, P. Choi, J.H. Lee, and G. Lim. An FET-type charge sensor for highly sensitive detection of DNA sequence. Biosensors and Bioelectronics, 20(1):69-74, 2004.
    [18] S.V. Dzyadevych , A.P. Soldatkin, A.V. El’skaya, C. Martelet, and N. Ja.rezic-Renault. “Enzyme biosensors based on ion-selective field-effect transistors.” Analytical Chimica Acta, vol.568, pp. 248-258, 2006 .
    [19] P. Fromherz, and A.O. enhausser. “A neuron-silicon junction: A Retzius cell of the leech on an insulated-gate field-effect transistor.” SCIENCE, vol. 252, pp. 1290-1293, 1990.
    [20] M. Hutzler, and P. Fromherz “Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus.” European Journal of Neuroscience, vol.19, pp. 2231-2238, 2004.
    [21] R. Harrison and C. Charles, “A low-power low-noise CMOS amplifier for neural recording applications,” IEEE Journal of Solid-State Circuits , vol. 38, no. 6, pp. 958–965, 2003.
    [22] F. Heer and et. al., “Cmos microelectrode array for bidirectional interaction with neuronal networks,” IEEE Journal of Solid-State Circuits, vol. 41, no. 7, pp. 1620–1629, 2006.
    [23] F. Zhang Holleman, and Otis, B.P. J. “Design of Ultra-Low Power Biopotential Amplifiersfor Biosignal Acquisition Applications” IEEE Journal of Biomedical Circuits and Systems, vol. 6, no.4, pp. 344-355, 2012.
    [24] R. R. Harrison, “A Versatile Integrated Circuit for the Acquisition of Biopotentials.” Custom Integrated Circuits Conference, CICC '07. IEEE pp.115-122, 2007
    [25] M.J. Deen, and O. Marinov, “Effect of forward and reverse substrate biasing on low-frequency noise in silicon PMOSFETs.” IEEE Transactions on Electron Devices, vol. 9, pp.408-413, 2002.
    [26] “Neuron basic”[online]. Available: www.mindcretors.com /NeuronBasic.htm
    [27] W. Rutten, “Selective electrical interfaces with the nervous system,”Annual Review Biomedical Engineering, pp. 407–452, 2002.
    [28] A. Branner, R. Stein, and R. Normann, “Selective stimulation of cat sciatic nerve using an array of varying-length microelectrodes,” J. Neurophysiology, vol. 85, pp. 1585–1594, 2001.
    [29] B. Besel and P. Fromherz, “Transistor array with an organotypic brain slice: field potential records and synaptic currents,” European Journal of Neuroscience, vol. 15, no. 6, pp. 999–1005, 2002.
    [30] M. Jenkner, B. M¨uller, and P. Fromherz, “Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses,” Biological Cybernetics, vol. 84, no. 4, pp.239–249, 2001.
    [31] S. Vassanelli and P. Fromherz, “Transistor records of excitable neurons from rat brain,” Applied Physics A: Materials Science & Processing, vol. 66, no. 4, pp. 459–463, 1998.
    [32] Datasheet of 0.35um 2P4M process, TSMC, 2006.
    [33] K. Williams and R. Muller, “Etch rates for micromachining processing,” Journal of Microelec-tromechanical Systems, , vol. 5, no. 4, pp. 256–269, 1996.
    [34] K. Williams, “Etch rates for micromachining processing- partΠ,” Journal of Microelectromechanical Systems, vol. 12, no. 6, pp. 761–778, 2003.
    [35] J. Bausells, ; J. Ca rrabina, ; A. Errachid, and A. Merlos. “Ion-sensitive field-effect transistors fabricated in a commercial cmos technology.” Sensors and Actuators B, vol.57, pp.56-62, 1999.
    [36]. P.A. Hammond, D. Ali, and D.R.S. Cumming. “Design of a single-chip ph sensor using a conventional 0.6-um cmos process.” IEEE SENSORS JOURNAL, vol.4, no.6, pp.706-712, 2004
    [37] P.A. Hammond, D. Ali, and D.R.S. Cumming. “A system-on-chip digital ph meter for use in a 271 wireless diagnostic capsule.” IEEE Transactions on Biomedical Engineering, vol.52, no.4, pp.687-694, 2005.
    [38] P. Bergveld. “Development, operation, and application of the ion-sensitive field-effect transistor as tool for electrophysiology.” IEEE Transactions on Biomedical Engineering, vol.19, no.5, pp.342-351,1972.
    [39] M. Banu and Y. Tsividis, “Floating voltage-controlled resistors in CMOS technology,”Electronics Letters, vol. 18, p. 678, 1982.
    [40] R. Harrison, “A Versatile Integrated Circuit for the Acquisition of Biopotentials,” Custom Integrated Circuits Conference, CICC’07. IEEE, pp. 115–122, 2007.
    [41] P. Allen and D. Holberg, CMOS analog circuit design. Oxford University Press New York, 2002.
    [42] C. Mora Lopez, et. al., “A 16-channel low-noise programmable system for the recording of neural signals .” IEEE International Symposium on Circuits and Systems, pp. 1451 - 1454, 2011.
    [43] J. Holleman, et. al., “A sub-microwatt low-noise amplifier for neural recording.” Conf Proc IEEE EMBS, pp.3930-3933, 2007
    [44] Y. Nemirovsky, I. Brouk, and C. Jakobson, “1/f noise in cmos transistors for analog applications,”IEEE Trans. Electron Device., vol. 48, no. 5, pp. 921 – 927, 2001.
    [45] J. S. Lin, S. R. Chang, C. H. Chang,, and H. Chen, “CMOS-micromachined, Two-dimenisional Transistor Arrays for Neural Recording and Stimulation.” Conf Proc IEEE EMBS, pp. 2365-2368, 2007.
    [46] P. Bergveld, ‘The future of biosensors”. Sensors and Actuators A: Physical, vol. 56, pp. 65-73, 1996.
    [47] E. A. Vittoz, “MOS transistors operated in the lateral bipolar mode and their application in CMOS technology.” IEEE J. Solid-State Circuit, vol.18, pp.273–279, 1983.
    [48] D. MacSweeney, K.G. McCarthy, A. Mathewson, and B. Mason, “A SPICE compatible subcircuit model for lateral bipolar transistors in a CMOS process.” IEEE Trans. Electron Device., vol.45, pp.1978–1984, 1998
    [49] W.Y. Chung, ; C.H. Yang,; D.G. Pijanowska,; P.B. Grabiec,; W. Torbicz, “ISFET performance enhancement by using the improved circuit techniques.” Sensors and Actuators B: Chemical, vol.113, pp.555–562, 2006
    [50] M.J. Deen, O. Marinov, ‘”Effect of forward and reverse substrate biasing on low-frequency noise in silicon PMOSFETs” IEEE Trans. Electron Dev., vol.49, pp.409–413, 2002.

    無法下載圖示 全文公開日期 本全文未授權公開 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)
    全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
    QR CODE