CMOS-Integrated Fluorescence Biochip Arrays

CMOS集成荧光生物芯片阵列 摘要 阵列技术已经为基因组学和蛋白质组学的大量发现负责。 然而，它们需要复杂且高度精确的仪器。今天，笨重，成本， 阵列读取器的复杂性已经成为其在护理点（Point-of-Care，简称POS）应用中采用的障碍。有 因此，对坚固、便携、低成本和易于使用的系统有着巨大的需求，这些系统可以在核心之外使用 设施 在本提案中，我们将针对该问题开发半导体集成解决方案：CMOS集成 荧光生物芯片该系统通过集成黄金标准检测， 使用市售常规半导体的生物技术模式（荧光检测） 制造工艺（互补金属氧化物半导体，CMOS）。所述有源阵列基板 不仅包括传感所需的单个传感器，而且还包括低噪声和高 动态范围传感器电路和电子信号分析块。我们的初步结果显示 通过使用CMOS，我们不仅可以提供前所未有的检测动态范围， 使得集成生物芯片阵列的成本可以忽略。后者是一个真正独特的标准，因为它证明了 通过允许生物芯片阵列（有效地为读取器）是一次性的，这是集成努力的结果。 在第一阶段计划中，我们计划设计和优化一个广泛使用的DNA生物芯片系统， 在分子诊断应用中具有<1000个DNA捕获点的微阵列。集成生物芯片将 能够在可见光范围内（λ = 400 nm至 800 nm），阵列尺寸为1000，像素间距为100 μ m。本项目的具体任务是：（1） 设计和制造这种CMOS生物芯片所需的电子电路，（2）集成 发射过滤器，（3）优化表面功能化方案，以及（4）创建微阵列兼容的 流体模块，用于无缝实验。 我们的第一阶段SBIR的最终定量目标是实验验证整个系统的DNA 微阵列应用，并进一步发展和商业化这一技术的第二阶段。

CMOS-Integrated Fluorescence Biochip Arrays Abstract Array technologies have been responsible for a multitude of discoveries in genomics and proteomics. However, they require sophisticated and highly accurate instrumentation. Today, the bulkiness, cost, and complexity of array readers have become barriers to their adoption in point-of-care (PoC) applications. There is thus a huge demand for rugged, portable, low cost, and ease-of-use systems that can be used outside of core facilities. In this proposal, we will develop a semiconductor-integrated solution for this problem: a CMOS-integrated fluorescence biochip. This system offers the "best of both worlds" by integrating the gold standard detection modality of biotechnology (fluorescence detection) with commercially available, conventional semiconductor manufacturing processes (complementary metal-oxide-semiconductor, CMOS). The active array substrates include not only the individual transducers required for sensing, but also the low-noise and high dynamic range sensor circuitry and electronic signal analysis blocks. Our preliminary results have demonstrated that by using CMOS, we will not only offer unprecedented detection dynamic range, but also make the cost of the integrated biochip arrays negligible. The latter is a truly unique criterion, as it justifies integration efforts by allowing the biochip array (effectively the reader) to be disposable. In this Phase I project, we plan to design and optimize a biochip system for the widely used DNA microarrays in molecular diagnostics applications with <1000 DNA capturing spots. The integrated biochip will be capable of high performance and multicolor fluorescence detection within the visible-range (¿=400nm to 800nm) with an array size of 1000 and a pixel pitch of 100 ¿m. The specific tasks in this project will be to (1) design and fabricate the electronics circuits that are required for such CMOS biochips, (2) integrate the emission filter, (3) optimize the surface functionalization protocols, and (4) create a microarray-compatible fluidics module for seamless experimentation. Our ultimate quantitative goal of this Phase I SBIR is to experimentally validate the whole system for DNA microarray applications and further develop and commercialize this technology in Phase II.