CMOS-Integrated Fluorescence Biochip Arrays

CMOS型集成荧光生物芯片阵列 摘要 阵列技术在基因组学和蛋白质组学方面取得了大量的发现。 然而，它们需要复杂和高度精确的仪器。如今，庞大的体积、成本和 阵列读取器的复杂性已成为其在医疗点(PoC)应用中采用的障碍。的确有 因此，对可在核心之外使用的坚固、便携、低成本和易用系统的需求巨大 设施。 在这个方案中，我们将为这个问题开发一个半导体集成的解决方案：一个集成的cmos 荧光生物芯片。该系统通过集成黄金标准检测来提供“两全其美” 使用市面上可买到的常规半导体的生物技术(荧光检测)模式 制造工艺(互补金属-氧化物-半导体、CMOS)。该有源阵列基板 不仅包括传感所需的单个传感器，还包括低噪声和高噪声 动态范围传感器电路和电子信号分析模块。我们的初步结果是 展示了通过使用CMOS，我们不仅将提供前所未有的检测动态范围，而且还将 使得集成生物芯片阵列的成本可以忽略不计。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(实际上是读取器)是一次性的，从而实现集成。 在这个第一阶段的项目中，我们计划为广泛使用的DNA设计和优化一个生物芯片系统 具有1000个DNA捕获点的分子诊断应用中的微阵列。集成的生物芯片将 能够在可见范围内(？=400 nm到？)进行高性能和多色荧光检测 800 nm)，阵列大小为1000，像素间距为100？m。本项目的具体任务为：(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)创建与微阵列兼容的 用于无缝实验的流体模块。 我们第一阶段SBIR的最终定量目标是通过实验验证整个系统的DNA 微阵列应用，并在第二阶段进一步开发和商业化这项技术。

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.