IEEE Trans Biomed Circuits Syst. 2021 Jun;15(3):369-379. doi: 10.1109/TBCAS.2021.3083359. Epub 2021 Aug 12.
We present a CMOS biochip-based photometer for quantitative immunoassay diagnostics. The photometer quantifies the concentration of antigens based on light absorption, which allows for a low-cost implementation without expensive optical components. We propose a light controller to lower the start-up and settling time of the light source to 30 seconds, to facilitate fast measurement starts, and to decrease the overall measurement times. The application-specific integrated circuit (ASIC) contains a 6 x 7-sensor array with 100 μm x 100 μm photodiodes that serve as signal transducers. The ASIC was developed in a normal 0.35- μm CMOS technology, avoiding the need for expensive post-CMOS processes. We present our strategy for the assembly of the ASIC and the immobilization of antibodies. For its first time, we demonstrate the quantification of prostate specific antigen (PSA) with an optoelectronic CMOS biochip using this approach. A PSA immunoassay is performed on the top surface of the CMOS sensor array, enzyme kinetics and PSA concentration are measured within 6 minutes with a limit of detection (LoD) of 0.5 ng/ml, which meets clinical testing requirements. We achieve an overall coefficient of variation (CV) of 7%, which is good compared to other point-of-care (PoC) systems.
我们提出了一种基于 CMOS 生物芯片的光电比色计，用于定量免疫分析诊断。该光电比色计基于光吸收来量化抗原浓度，从而实现了低成本的实现，无需昂贵的光学元件。我们提出了一种光源控制器，可将光源的启动和稳定时间降低到 30 秒，以方便快速进行测量，并减少整体测量时间。专用集成电路 (ASIC) 包含一个 6x7 传感器阵列，每个传感器由 100μm x 100μm 的光电二极管组成，用作信号转换器。该 ASIC 是在标准的 0.35-μm CMOS 技术中开发的，避免了昂贵的后 CMOS 工艺的需求。我们介绍了 ASIC 的组装和抗体固定的策略。我们首次展示了使用这种方法通过光电 CMOS 生物芯片对前列腺特异性抗原 (PSA) 的定量检测。在 CMOS 传感器阵列的顶表面上进行 PSA 免疫分析，在 6 分钟内测量酶动力学和 PSA 浓度，检测限 (LoD) 为 0.5ng/ml，满足临床测试要求。我们实现了总体变异系数 (CV) 为 7%，与其他即时检测 (PoC) 系统相比表现良好。
