集成氧化锌薄膜晶体管的固态纳米孔单分子生物电荷传感器件

The detection of biomolecular charges at the single-molecular level may be realized by integrating field-effect transistors with solid-state nanopores, which may offer an important single-molecular research tool and therefore becomes a front of nanopore research. But so far such attempts have not been successful, mainly due to difficulties associated with physical effects such as ionic screening in solutions and grand challenges in device fabrications. This project for the first time proposes a novel type of solid-state nanopore devices, which integrate ZnO thin-film transistors (TFTs) into the inner walls of nanopores via atomic layer deposition method and thus detect charges of biomolecules passing through nanopores. This type of devices utilizes the conformal and flexible TFT fabrication processes and greatly reduces the difficulty of fabrications; the TFTs are integrated into the inner walls and thus can ensure biomolecule detection at close range with reduced effect of screening. We will study the key process steps, fabricate the devices, experimentally measure translocation signals from two types of molecules, lambda-DNA (negatively charged) and PEG (charge neutral), and compare and study the response of TFTs to the charges. Furthermore, we will combine experiments and simulations to study the effects of ionic concentrations and voltage biases, study and elucidate the sensing mechanisms as well as physical effects such as the field-effect coupling between biological charges and semiconductors and ionic screening. This project will be a new attempt to realize single bio-molecular charge sensing; the studied mechanisms, fabrication and measurement methods for this novel type of devices may provide new insights into the integration of microelectronics and nanopore technologies.

在固态纳米孔中集成场效应晶体管有可能检测单个生物分子的本征电荷，提供一种重要的单分子研究手段，因而成为纳米孔研究前沿。但迄今这方面努力尚未成功，主要困难在于溶液中离子屏蔽等物理效应及工艺上巨大挑战。本项目首次提出一种新型固态纳米孔器件，在孔壁内用原子层沉积法集成氧化锌薄膜晶体管（TFT）以检测过孔生物分子的电荷。该器件利用TFT工艺的保形性和灵活性极大降低工艺难度；且TFT集成在孔内壁，确保对生物分子近距离检测以减少屏蔽影响。我们将研究关键工艺、制备器件并实测lambda DNA（负电）及PEG（电中性）两类分子过孔信号，对比研判TFT对电荷的响应度；更进一步，将结合实验与仿真研究离子浓度、电偏压的影响，研究阐明传感机制及生物电荷与半导体场效应耦合、离子屏蔽等物理效应。本项目是为实现单分子生物电荷传感的新尝试；对该新型器件机理、工艺及测量手段的研究将为微电子与固态纳米孔的结合提供新思路。

在本课题中，我们在国际上首次提出并实现了内嵌集成垂直沟道氧化锌薄膜晶体管（TFT）的固态纳米孔器件，并用于基于电荷的生物分子过孔传感。我们探索开发了一整套器件工艺流程，包括采用溅射技术在10纳米厚的氮化硅薄膜正反面形成ITO源漏极、采用TEM技术穿透薄膜形成~40纳米的初始纳米孔、采用原子层沉积（ALD）工艺在孔内壁依次共型沉积10纳米厚的氧化锌半导体层和5纳米厚的氧化铝栅绝缘层、以及用含待测生物分子的离子溶液形成溶液栅极。通过工艺控制，最终形成的TFT纳米孔器件的晶体管沟道长度和纳米孔直径均达~10纳米范围。我们使用TFT纳米孔器件对分别lambda-DNA和牛血清白蛋白分子进行了过孔检测，并在离子阻塞电流和TFT晶体管电流两路同时检测到单分子过孔信号。对这两类分子，TFT信号呈现相反极性，与他们各自所携带的负电荷与正电荷相符。TFT信号也探测出DNA分子的折叠打结的高阶形态。我们进一步在不同电压和溶液离子浓度条件下进行过孔实验，揭示了TFT信号传感机制与传统的离子阻塞电流不同。通过分析信号统计并结合TCAD仿真，我们确认TFT信号与基于场效应的单生物分子电荷检测机制一致。电荷是生物分子的重要性质，并在其生理功能中起到及其广泛和关键的作用。本项目的完成是实现基于电荷的单生物分子传感技术的重要一步，在基础生物研究手段和早期疾病检测方面均有应用前景。