用於術中成像的基於駐波震盪器的可編程近場圖像傳感器

Abstract

在乳房腫瘤切除手術中，我們最關心的是腫瘤是否已完全切除。因此，腫瘤邊緣評估是必不可少的。快速的邊緣評估可以確保腫瘤被完全切除，並在手術過程中確認清晰的邊緣，並且能減少二次手術的可能性。為了達到診斷的準確性，圖像感測儀需要高解析度。此外，在癌症診斷中，深度解析度對於邊緣分析至關重要，以確定體內剩餘物的數量。換句話說，我們需要高解析度的三維成像儀。 以往的工作展示了用於細菌測量和指紋的2-D近場射頻成像儀帶有LC振盪器，但由於讀取方法的限制，其填充因子(filling factor)並不理想。至於三維感測，在過去的工作中使用了兩個垂直堆疊的螺旋感測器振盪器，但只能進行兩級深度感測。另一種方法使用電氣阻抗層析成像（EIT），但這僅適用於MHz頻率，不適用於腫瘤成像。我們通過實施一種新型的近場影像傳感器來解決上述挑戰。 本論文提出了一種新型的三維射頻近場影像傳感器，用於乳腺癌手術中的術中成像，包括快速邊緣評估和深度解析度。與以前的技術相比，射頻近場影像傳感器的解析度和填充因子得到了改善。我們提出了一種以場可編程差分傳輸線（t-line）配置為駐波振盪器（SWO）傳感器的方法，以實現64％填充因子下的51.2μm × 50μm像素解析度和1μm深度解析度。我們通過使用NMOS電晶體調製來自傳輸線的電場。駐波振盪器傳感器以13GHz運行，因為腫瘤和正常組織的介電常數在這個頻率下變化最為明顯。 該圖像儀包括除64除頻鏈和32位頻率計數器和串行器作為讀出。此圖像儀是在180nm CMOS技術中實現的，每個駐波振盪器傳感器的總功率為107.8毫瓦（或4.9毫瓦/像素）。我們在PCB背面使用散熱器來維持效能。此外，在40毫秒的門時間下，測量的Allan偏差達到0.54 ppm的噪聲底線(noise floor)。我們使用去離子水和異丙醇（IPA）的混合物進行液體校準，以研究傳感器的靈敏度。 我們採用後CMOS等離子增強化學氣相沉積（PECVD）來對芯片表面進行20nm的保護層塗覆，以保護所有電極，並以生物相容性環氧樹脂（Epo-Tek 302-3M）將晶片整合在PCB板以便進行生物測量。我們呈現了帶有迂曲微流道和正福林中白血病腫瘤的初步2-D圖像結果。我們通過使用變形的微流道，驗證了三維感測功能。我們還使用琼脂凝膠樣本呈現了三維成像結果。

In breast tumor removal surgery, what we are most concerned about is whether the tumor has been completely removed. Therefore, tumor margin assessment is essential. Rapid margin assessment can ensure the complete removal of the tumor and reduce the likelihood of a second surgery by confirming clear margins during the operation. For diagnostic accuracy, high resolution is required. In addition, depth resolution is crucial for margin analysis in cancer diagnosis to ascertain the quantity of remaining residue inside the body. In other words, a high-resolution 3-D imager is needed. Previous work demonstrates the 2-D Near-field RF imager with an LC oscillator for bacteria measurement and fingerprint. However, due to limitations in the readout method, their filling factor was not optimal. As for 3-D sensing, past work employs two vertically-stacked spiral inductors oscillator sensor but it can only perform two-level depth-sensing. And the other one uses electrical impedance tomography (EIT), but this can only work in MHz, which is not suitable for tumor imaging. We address the challenges above by implementing a new type of near-field image sensor. This thesis presents a new type of 3-D RF near-field image sensor for intraoperative imaging including rapid margin assessment and depth resolution in breast cancer surgery. The RF near-field image sensor has improved resolution and filling factor compared to previous technologies. We propose a field-programmable differential transmission line (t-line) configured as a standing-wave oscillator (SWO) sensor to achieve 51.2μm × 50μm pixel resolution at 64% filling factor and 1μm depth resolution. We modulate E-fields from a transmission line with NMOS transistors. The Standing-wave oscillator sensor operates at 13-GHz because the dielectric constant changes of tumor and normal tissue are most pronounced at this frequency. The imager includes divide-by-64 frequency divider chains and a 32-bit frequency counter and serializer as the readout. This work is implemented in 180-nm CMOS technology and each SWO sensing chain consumes a total power of 107.8 mW (or 4.9 mW/pixel). A heat sink is applied from the PCB backside. The measured Allan Deviation achieves a noise floor of 0.54 ppm at a gate time of 40 msec. Liquid calibration using a mixture of de-ionized water and isopropyl alcohol (IPA) is utilized to study the sensor sensitivity. We adopt post-CMOS Plasma Enhanced Chemical Vapor Deposition (PECVD) to coat the chip surface with a 20nm passivation layer to achieve all the electrodes protected and use biocompatible epoxy (Epo-Tek 302-3M) for bio-measurements. We demonstrate 2-D image with a meander microfluidic channel and a preliminary 2-D image result of Leukemia Cancer Tumor in formalin. 3-D function capability is verified by using the deformed microfluidic channel. We demonstrate 3-D imaging with agar gel phantom.