用于综合生物分子处理的全集成无气无磁 CMOS 铁流体平台。

Dongwon Lee, Fuze Jiang, Hangxing Liu, Kyung-Sik Choi, Doohwan Jung, Ying Kong, Marco Saif, Zhikai Huang, Jing Wang, Hua Wang
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摘要

本文介绍了一种完全集成的 CMOS 铁流体平台,该平台具有片上三电极电化学电池、温度调节器和磁传感器。拟议的平台由 25 个铁流体像素和 2 个磁传感器组成。每个铁流体像素包括一个螺旋感应器、一个三电极电化学电池、一个温度传感器和一个局部焦耳加热器。与基于气动的平台不同,这种铁流体平台不需要外部气动泵来驱动液滴。相反,片上螺旋电感器产生磁场来操纵铁流体液滴。此外,这些电感器还可用作热辐射器。CMOS 铁流体平台采用 45 纳米 CMOS SOI 工艺实现。对铁流体控制和磁感应进行了理论分析,以了解铁流体运动条件与集成磁传感器之间的关系。使用不同浓度的亚甲基蓝溶液对片上电化学恒电位仪进行了表征,并测量了电化学传感器的变化。作为概念验证,演示了使用片上实时重组酶聚合酶扩增(RT-RPA)进行生物测量。拟议的平台为铁流体操作、传感和温度调节提供了完全集成的解决方案,无需外部笨重的设备,从而支持先进的生物分子处理。虽然 RT-RPA 在此仅用于演示目的,但我们的铁流体多功能 CMOS 阵列平台也能够处理其他多种分子分析物。这种多功能性凸显了该平台在分子诊断和生物分析研究领域的广泛应用潜力。
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Fully Integrated Pneumatic-Free and Magnet-Free CMOS Ferrofluidic Platform for Comprehensive Biomolecular Processing.

This article presents a fully integrated CMOS ferrofluidic platform featuring on-chip three-electrode electrochemical cells, temperature regulators, and magnetic sensors. The proposed platform consists of 25 ferrofluidic pixels and 2 magnetic sensors. Each ferrofluidic pixel comprises a spiral inductor, a three-electrode electrochemical cell, a temperature sensor, and a localized Joule heater. Unlike pneumatic-based platforms, this ferrofluidic platform does not require an external pneumatic pump to drive droplets. Instead, the on-chip spiral inductors generate magnetic fields to manipulate the ferrofluidic droplets. Additionally, these inductors are repurposed as heat radiators. The CMOS ferrofluidic platform is implemented using a 45-nm CMOS SOI process. Theoretical analyses of ferrofluidic control and magnetic sensing are conducted to understand the relationship between ferrofluidic movement conditions and the integrated magnetic sensor. The on-chip electrochemical potentiostat is characterized using various concentrations of methylene blue solution, and the variation in the electrochemical sensor is measured. As proof of concept, biological measurements with on-chip real-time recombinase polymerase amplification (RT-RPA) are demonstrated. The proposed platform offers a fully integrated solution for ferrofluidic manipulation, sensing, and temperature regulation without the need for external bulky equipment, thereby supporting advanced biomolecular processing. While RT-RPA is used here solely for demonstration purposes, our ferrofluidic multi-functional CMOS array platform is also capable of processing a wide range of other molecular analytes. This versatility underscores the platform's potential for broad applications in molecular diagnostics and bioanalytical research.

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