申请人:The Trustees of Columbia University In The City Of New York
公开号:US10718732B2
公开(公告)日:2020-07-21
Electrochemical sensing of biomolecules eliminates the need for bulky optical instruments required in traditional fluorescence-based sensing assays. Integration of the sensor interface electrodes and active electrochemical detection circuitry on CMOS substrates miniaturizes the sensing platform, enhancing portability for point-of-care applications, while enabling high-throughput, highly-parallel analysis. One embodiment includes a four-by-four active sensor array for multiplexed electrochemical biomolecular detection in a standard 0.25-μm CMOS process. Integrated potentiostats, including control amplifiers and dual-slope ADCs, stimulate the electrochemical cell and detect the current flowing through on-chip gold electrodes at each sensor site resulting from biomolecular reactions occurring on the chip surface. Post-processing techniques for fabricating biologically-compatible surface-electrode arrays in CMOS that can withstand operation in harsh electrochemical environments are described. Demonstrations showing example operation of the active CMOS array for biomolecular detection include cyclic voltammetry of a reversible redox species, DNA probe density characterization, and quantitative and specific DNA hybridization detection in real time.
生物大分子的电化学传感无需使用传统荧光传感检测所需的笨重光学仪器。将传感器接口电极和有源电化学检测电路集成到 CMOS 基底面上,可使传感平台小型化,增强了护理点应用的便携性,同时实现了高通量、高并行分析。其中一个实施方案包括一个四乘四的有源传感器阵列,用于在标准 0.25μm CMOS 工艺中进行多路复用电化学生物分子检测。集成的恒电位仪(包括控制放大器和双斜率模数转换器)可刺激电化学电池,并检测芯片表面发生的生物分子反应所产生的流经每个传感器位置的片上金电极的电流。介绍了在 CMOS 中制造生物兼容表面电极阵列的后处理技术,这种阵列可在恶劣的电化学环境中运行。示例显示了用于生物分子检测的有源 CMOS 阵列的运行情况,包括可逆氧化还原物种的循环伏安法、DNA 探针密度表征以及定量和特异性 DNA 杂交实时检测。