Lagrangian detection of biomolecular interactions

描述(由申请人提供)：基因表达模式和蛋白质图谱目前正在彻底改变对生物学和疾病的理解，并有可能成为诊断和预后的工具。一旦建立了这些模式，将需要实现它们的方法。我们设计了一个平台，可以将未知样本的特征与已建立的表达或蛋白质图谱快速匹配。该方法的特点是对图案特征进行计算机控制的测试，并采用自适应反馈来提高灵敏度和可靠性。它将在识别根据关键分子结构的存在或浓度描述的已建立的模式方面具有最大的效用。 目前用于未知样本分析的高通量方法，如用于基因表达分析的DNA微阵列，可以被描述为欧拉设计-已知的捕获探针通过附着在固体底物上而固定在空间中，并通过目标扩散进行杂交。生物识别只查询目标溶液的一小部分是低效的，目标-探针相互作用发生得很慢，并且目标-探针结合发生在统一的条件下。本申请描述了另一种拉格朗日设计-将探针布置在细丝上，并通过纳升反应区移动，以进行生物识别测试、处理和分析。极小的尺寸实现了完全、快速和完全的目标-探测器相互作用。灵活和自适应的特征允许为每个捕获探针-目标相互作用量身定制反应条件。 我们已经确定了这一新平台技术成功的几个关键组件。其中包括合适纤维的鉴定、探头的沉积、带有不相容表面张力阀的小体积反应室的开发，以及用于通过多个反应室的计算机控制的纤维输送的专用设备。尽管我们有有限的实验数据，但我们确实有的数据表明，拟议系统的每个关键组件都是可行的。 这项技术将为识别基因表达或蛋白质图谱中存在的模式提供一种新的工具，使这些图谱能够充分用于诊断和预后目的。

DESCRIPTION (provided by applicant): Patterns of gene expression and protein profiles are currently revolutionizing the understanding of biology and disease and are likely to become diagnostic and prognostic tools. Once these patterns are established, methods to implement them will be required. We have designed a platform which rapidly matches the characteristics of an unknown sample with established expression or protein profiles. The approach is characterized by computer controlled testing for pattern features with adaptive feedback to increase sensitivity and reliability. It will have greatest utility for identifying established patterns described in terms of the presence or concentration of 100s to 1000s of key molecular structures. Current high-throughput methods for profiling of an unknown sample, such as DNA microarrays for gene expression profiling, can be characterized as Eulerian design - known capture probes are fixed in space by attachment to a solid substrate and hybridized by target diffusion. Biorecognition is inefficient querying only a fraction of the target solution, target-probe interactions occur slowly, and target-probe binding occurs under uniform conditions. This application describes an alternative Lagrangian design - probes are arranged on a filament and moved through nanoliter reaction zones for biorecognition testing, processing, and analysis. The extremely small dimensions enable complete, rapid, and complete target-probe interactions. The flexible and adaptive features permit tailoring reaction conditions to each capture probe-target interaction. We have identified several key components that are critical to the success of this new platform technology. These are the identification of an appropriate fiber, deposition of probe, development of the small volume reaction compartment with immiscible surface tension valves, and a specialized apparatus for computer controlled fiber transport through multiple reaction chambers. Although we have limited experimental data, the data we do have, suggests that each of the key components of the proposed system is feasible. This technology will provide a new tool for the identification of patterns present in gene expression or protein profiles enabling these profiles to be fully utilized for diagnostic and prognostic purposes.