CMOS-Based Electrokinetic Microfluidics With Multi-Modal Cellular and Bio-Molecular Sensing for End-to-End Point-of-Care System

CMOS-Based Electrokinetic Microfluidics With Multi-Modal Cellular and Bio-Molecular Sensing for End-to-End Point-of-Care System
复制标题

基于 CMOS 的电动微流体,具有多模式细胞和生物分子传感,适用于端到端护理点系统

DOI:
10.1109/tbcas.2021.3136165
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发表时间:
2021
影响因子:
5.1
通讯作者:
Sengupta, Kaushik
Sengupta, Kaushik
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhu, Chengjie;Maldonado, Jesus;Sengupta, Kaushik

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新型冠状病毒肺炎(COVID-19,即2019冠状病毒病)大流行爆发后,能够快速分析的床旁(POC)生物分子诊断的重要性变得非常明显。虽然用于基于蛋白质和核酸的测定的感测接口已经用芯片级系统证明,但紧凑形状因子的样品制备通常是实现端到端POC诊断的主要瓶颈。端到端系统的小型化需要解决前端样品处理问题,如果没有前端样品处理,低成本POC诊断的目标仍然难以实现。在本文中,我们解决了大量的流体处理与AC-渗透的电动流体流,可以完全控制,处理和自动化的CMOS集成电路,在台积电65纳米LP工艺制造。在这里,我们结合了联合收割机大量的流体流量控制与生物分子传感,细胞操作,细胞计数和分离,所有这些都是控制与硅芯片的所有功能于一身的生物传感设备。在100 × 50 m2的微流通道中,实现了CMOS控制的无湍流体相流体流动,流体速度可达160 m/s。我们结合电极阵列,以允许精确控制和聚焦细胞流(2米精度),用于稳健的细胞计数和后续分离。我们还将一个16元阻抗谱接收器阵列的细胞和无标记的蛋白质传感。CMOS驱动的微流体、操纵和传感的巨大可扩展性可以带来新的设计空间和一类新的小型化传感技术。
The importance of point-of-care (POC) bio-molecular diagnostics capable of rapid analysis has become abundantly evident after the outbreak of the Covid-19 pandemic. While sensing interfaces for both protein and nucleic-acid based assays have been demonstrated with chip-scale systems, sample preparation in compact form factor has often been a major bottleneck in enabling end-to-end POC diagnostics. Miniaturization of an end-to-end system requires addressing the front-end sample processing, without which, the goal for low-cost POC diagnostics remain elusive. In this paper, we address bulk fluid processing with AC-osmotic based electrokinetic fluid flows that can be fully controlled, processed and automated by CMOS ICs, fabricated in TSMC 65 nm LP process. Here, we combine bulk fluid flow control with bio-molecular sensing, cell manipulation, cytometry, and separation—all of which are controlled with silicon chips for an all-in-one bio-sensing device. We show CMOS controlled pneumatic-free bulk fluid flow with fluid velocities reaching up to 160m/s within a microfluidic channel of 100 × 50mof cross-sectional area. We incorporate electrode arrays to allow precise control and focused cell flows (2m precision) for robust cytometry, and for subsequent separation. We also incorporate a 16-element impedance spectroscopy receiver array for cell and label-free protein sensing. The massive scalability of CMOS-driven microfluidics, manipulation, and sensing can lead to a new design space and a new class of miniaturized sensing technologies.