CMOS biosensor system for on-chip cell culture with read-out circuitry and microfluidic packaging

CMOS biosensor system for on-chip cell culture with read-out circuitry and microfluidic packaging
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用于片上细胞培养的 CMOS 生物传感器系统,具有读出电路和微流体封装

DOI:
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发表时间:
2012
期刊:
Annual International Conference of the IEEE Engineering in Medicine and Biology Society
影响因子:
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通讯作者:
J. Christen
J. Christen
中科院分区:
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文献类型:
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作者:
D. Welch;J. Christen

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设计了带有传感器的 1.5 mm × 3 mm CMOS 芯片,用于监测片上细胞培养物。该芯片采用 0.5 μm CMOS 工艺设计,具有 3 层金属层和 2 层多晶硅层,采用 5 伏工艺。该芯片包含离子敏感场效应晶体管 (ISFET) 以及带有读出电路的 ISFET,用于监测芯片顶部溶液的 pH 值。叉指电极结构 (IDES) 使用该工艺的顶部金属制成,用于通过阻抗感测细胞附着和增殖。包括 IDES 读出电路和 IDES 测试结构。该芯片还包含测试放大器、带隙参考测试结构以及用于后处理的连接。我们设计的芯片能够适应封装到直接暴露于细胞培养环境的环境中。具体来说,我们设计的芯片在芯片中心附近集成了传感器,从而可以使用环氧树脂或类似材料密封芯片边缘周围的连接,以防止短路。我们放大器的初步电气特性结果表明增益为 48 dB、带宽为 1.65 kHz、共模抑制比 (CMRR) 为 72 dB。我们还提出了一种使用柔性 PCB 基板的封装技术。
A 1.5 mm × 3 mm CMOS chip with sensors for monitoring on-chip cell cultures has been designed. The chip is designed in a 0.5 μm CMOS process which has 3 metal layers and 2 poly layers and is a 5 volt process. The chip contains ion sensitive field effect transistors (ISFETs), as well as ISFETs with read-out circuitry, for monitoring the pH of solutions placed on top of the chip. Interdigitated electrode structures (IDESs) are made using the top metal of the process to be used for sensing cellular attachment and proliferation via impendence. IDES read-out circuits and IDES test structures are included. The chip also contains test amplifiers, bandgap reference test structures, and connections for post-processing. We designed the chip to accommodate packaging into an environment where it will be directly exposed to a cell culture environment. Specifically we designed the chip to have the incorporated sensors near the center of the chip allowing for connections made around the edge of the chip to be sealed off using an epoxy or similar material to prevent shorting. Preliminary electrical characterization results for our amplifier indicate a gain of 48 dB, a bandwidth of 1.65 kHz, and a common mode rejection ratio (CMRR) of 72 dB. We also present a packaging technique using a flexible pcb substrate.
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