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Light Absorption Measurement With a CMOS Biochip for Quantitative Immunoassay Based Point-of-Care Applications
IEEE Transactions on Biomedical Circuits and Systems ( IF 3.8 ) Pub Date : 2021-05-25 , DOI: 10.1109/tbcas.2021.3083359
Alexander Hofmann , Michael Meister , Alexander Rolapp , Peggy Reich , Friedrich Scholz , Eric Schafer

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 μ\boldsymbol{\mu }m x 100 μ\boldsymbol{\mu }m photodiodes that serve as signal transducers. The ASIC was developed in a normal 0.35-μ\boldsymbol{\mu }m 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.

中文翻译:


使用 CMOS 生物芯片进行光吸收测量,用于基于定量免疫分析的护理点应用



我们推出了一种基于 CMOS 生物芯片的光度计,用于定量免疫分析诊断。该光度计根据光吸收来量化抗原浓度,从而无需昂贵的光学元件即可实现低成本实施。我们提出了一种光控制器,可将光源的启动和稳定时间降低至 30 秒,以促进快速测量启动,并减少总体测量时间。专用集成电路 (ASIC) 包含一个 6 x 7 传感器阵列,该阵列具有 100 μ\boldsymbol{\mu }mx 100 μ\boldsymbol{\mu }m 光电二极管,用作信号传感器。该 ASIC 采用普通 0.35-μ\boldsymbol{\mu }m CMOS 技术开发,无需昂贵的后 CMOS 工艺。我们提出了 ASIC 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) 进行定量。在CMOS传感器阵列的顶面进行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0.5 ng/ml,满足临床测试要求。我们的总体变异系数 (CV) 为 7%,与其他即时护理 (PoC) 系统相比,这已经相当不错了。
更新日期:2021-05-25
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