Coincident Gas Detector for Auger and Beta Electrons

描述(申请人提供)：我们实现了多粒子检测系统(MPD)，它使免疫分析(IA/MPD)的灵敏度提高了约500倍，降至1 fg/ml。拟议的基于GAS的MPD实现将允许吞吐量增加约10倍，并进一步提高灵敏度。此外，所提出的检测系统几乎是诊断蛋白质组学应用的理想选择。我们将基于GAS的MPD读取器实现到增强型P芯片(P芯片/MPD)。 然而，对生物医学界来说，更重要的将是新探测器的使能特性。它将使一个研究蛋白质-蛋白质相互作用的专有系统比目前的技术灵敏数百倍。这种蛋白质-蛋白质相互作用定量系统利用MPD精致的仪器灵敏度，即使对低丰度蛋白质也能实现最高灵敏度的检测和合理的吞吐量。超高的灵敏度和极大的动态范围相结合，使俄歇电子介导的能量转移方法(AEMET)远远优于其他功能蛋白质组学方法。这一过程的特殊性质使我们能够估计从“供体”分子到“受体”分子的距离。在另一实施方式中，它允许阐明特定大分子的完整性和拓扑构型。在适当的底物下，它允许非常具体地测量适当的酶对目标大分子的裂解。 这项提议中提出的发展中最重要的元素是创新的基于气体的电子探测器，它允许以方便的96孔格式同时测量许多蛋白质的相互作用。它以探测气体中的电子为基础，需要广泛的电子学和软件开发。

DESCRIPTION (provided by applicant): We implemented multiparticle detection system (MPD), which enabled the improvement of sensitivity of immunoassays (IA/MPD) by about a factor 500 down to 1 fg/ml. The proposed gas based implementation of MPD will permit the throughput increase about 10-fold, as well as some further increase of sensitivity. Furthermore, the proposed detection system is almost ideal for the diagnostic proteomics applications. We will implement gas based MPD Readers to enhanced P-chips (P-chips/MPD). However, even more important to biomedical community will be the enabling properties of new detector. It will enable a proprietary system for studies of protein-protein interactions that is about hundred times more sensitive than current techniques. This protein-protein interaction quantification system capitalizes on MPD's exquisite instrumental sensitivity to enable the highest sensitivity detection and reasonable throughput even for low abundance proteins. The ultra high sensitivity and very large dynamic range combine to make Auger Electrons Mediated Energy Transfer method (AEMET) far superior to other methods of functional proteomics. The particular properties of this process permit to estimate the distance from "donor" to "acceptor" molecule. In another implementation, it permits to elucidate the integrity and topological configuration of a particular macromolecule. With appropriate substrate, it permits to very specifically measure the cleavage of target macromolecules by appropriate enzymes. The most important element of the development proposed in this proposal is the innovative gas based detector of electrons, which permits in to measure in convenient 96 well format interactions of many proteins concurrently. It is based on detection of electrons in gas and will require extensive development of electronics and software.