抑制癲癇發作的雙極性刺激器以及在低電壓製程下負高壓產生器設計

Abstract

在臨床醫學上，生醫晶片的推動改變了多數醫療方法，也解決很多以往不能解決的疾病，例如植入視網膜晶片，使盲人重見光明。廣義來說，結合微電子技術、醫學以及生物化學，可以製造應用不同疾病醫療之生物晶片，例如癲癇晶片。

抑制癲癇的方法為輸出定電流抑制，然而電極植入不同大鼠腦組織之等效阻抗皆不同，必須做刺激器電路針對不同大鼠樣本皆能產生定電流週期性脈波輸出。在刺激器刺激下，需要一個相對應的反向電流使腦內電荷平衡，避免電極的氧化還原電荷影響人體。刺激方式分為兩種：兩根針(雙極性)刺激以及一根針(單極性)刺激。雙極性刺激為輸出高低電位之兩根電極做刺激，其高低電位會互換，使電流周期性地正負反向；單極性刺激為一根電極對地做刺激，當輸出刺激電流時電極輸出電壓為正電壓，反向電流時電極電壓為負電壓。

在具有雙極性刺激的癲癇晶片內，輸出級需要4~10V的高電壓，又系統晶片之供應電壓只有1.8V，必須建立直流-直流變壓器將1.8V升到4~10V之高壓以供應不同阻抗行電刺激。在此研究中提出在低電壓製程下實現負載適應性之變化，並內嵌入有效變頻可調式高壓產生器，一來降低電壓轉換率，使電極上電流不易發生突波；二來，在電極植入不深之情況下，在兩電極不同間距時可以有較低功耗。本刺激器可支援雙極性及單極性刺激，並加入數位類比轉換器調整輸出電流之大小以供動物實驗用。本次雙極性刺激器可選擇輸出電流20uA, 30uA和40uA，在刺激的電流30uA下可刺激的電極阻抗之電容值在4nF到200nF、10kΩ到250kΩ，並在TSMC 0.18um 1.8V/3.3V 低電壓製程下實現。

在生醫晶片單極性刺激下，需要一個負高壓產生器(~-8V)供給刺激器負電壓，而設計一個在低電壓製程不會造成閘極可靠度問題且無閂鎖效應之負高壓產生器是一件具有挑戰性的事情。本負高壓產生器可穩在-8V，其輸出電流可高達320uA，在負載電流200uA時功率轉換率為42.26%，電源電壓調整率為0.166V/V，負載調整率為0.194mV/uA。

Nowadays, the clinical therapy changes since the emerging of the biomedical chips. In addition, more diseases could be cured thanks to the invention, e.g. the artificial retina. By extension, the biomedical chip is made by the combination of microelectronics, medicine and biochemical such as epilepsy prosthetic SoC.

The methodology to suppress epilepsy seizure is constant current stimulation. However, there are different values of electrode-tissue impedance through different kinds of electrode and sample rat. The stimulus driver must provide the constant periodic current pulses to different rats and electrodes. For avoiding the electrochemical process to damage the tissue, the reversed current pulses which amplitude is equal to the stimulus current is required after stimulating. The stimulation methodology is divided into two types: two leads per site (bipolar stimulation) and one lead per site (monopolar stimulation). For bipolar stimulation, two electrodes supply high and low voltage to the tissue respectively. The voltage levels of two electrodes exchange periodically so that the stimulus current flowing through the tissue becomes positive or negative alternately. For monopolar stimulation, one electrode supplies the adaptive voltage to the ground. When stimulating, the electrode provides positive voltage to generate the positive stimulus current. After stimulating, the electrode provides negative voltage to generate the negative reversed current.

In epilepsy prosthetic SoC, the high voltage potential 4~10V is required in the output stage. However, the power supply of the SoC is only 1.8V. DC-DC boost converter should be required to raise the voltage potential for the stimulus driver. In the report, we introduce the stimulus driver with loading adaptive consideration in the low-voltage process. Besides, the positive high voltage generator with effective PFM controller is embedded within the stimulus driver to control the switching speed and dynamic power effectively. First, it reduces the slew rate to free from the glitch current on the electrode. Second, when stimulating, it consumes lower power within the electrode implanted shallower (low capacitance). The stimulus driver supports monopolar and bipolar stimulation. In addition, with DAC applied, the output stimulus current could be 20uA, 30uA and 40uA within the electrode-tissue impedance from 4nF to 200nF and from 20kΩ to 250kΩ at stimulus current 30uA in the TSMC 0.18um 1.8V/3.3V general purpose process.

In monopolar stimulation of biomedical chips, the negative high voltage generator (~-8V) is needed. With the potential for mass production, CMOS technologies are more attractive to realize the system on a chip (SoC). Therefore, the positive and negative high voltage generators should be feasible in the commercial low-voltage CMOS processes. The proposed negative high voltage generator could be regulated at -8V. The maximum output current is up to 320uA. When the output current is 200uA, the power efficiency is 42.26%. The line regulation is 0.166V/V. The load regulation is 0.194mV/uA.