Lagrangian detection of biomolecular interactions

描述（由申请人提供）：基因表达模式和蛋白质谱目前正在彻底改变对生物学和疾病的理解，并可能成为诊断和预后工具。一旦建立了这些模式，就需要实施这些模式的方法。我们设计了一个平台，可以快速将未知样品的特征与已建立的表达或蛋白质谱相匹配。该方法的特点是由计算机控制的测试模式的功能与自适应反馈，以增加灵敏度和可靠性。它将具有最大的实用性，用于识别根据100到1000个关键分子结构的存在或浓度描述的已建立的模式。 目前用于分析未知样品的高通量方法，例如用于基因表达分析的DNA微阵列，可以表征为欧拉设计-已知的捕获探针通过附着到固体基底上在空间中固定，并通过靶扩散杂交。生物识别是低效的，仅查询靶溶液的一部分，靶-探针相互作用缓慢发生，并且靶-探针结合在均匀条件下发生。本申请描述了一种替代的拉格朗日设计-探针被布置在细丝上并移动通过纳升反应区，用于生物识别测试、处理和分析。极小的尺寸使得能够实现完全、快速和完全的靶-探针相互作用。灵活和自适应的功能允许定制反应条件，以每个捕获探针-靶相互作用。 我们已经确定了对这种新平台技术的成功至关重要的几个关键组件。这些是一个适当的纤维，探针的沉积，小体积的反应室与不混溶的表面张力阀的发展，和一个专门的计算机控制的纤维运输通过多个反应室的设备的识别。虽然我们的实验数据有限，但我们所拥有的数据表明，所提出的系统的每个关键组件都是可行的。 这项技术将提供一种新的工具，用于识别基因表达或蛋白质谱中存在的模式，使这些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.