Coincident Gas Detector for Auger and Beta Electrons

描述（由申请人提供）：我们实施了多粒子检测系统（MPD），其能够将免疫测定（IA/MPD）的灵敏度提高约500倍，低至1 fg/ml。所提出的基于气体的MPD实施将允许吞吐量增加约10倍，以及灵敏度的进一步增加。此外，所提出的检测系统几乎是理想的诊断蛋白质组学应用。我们将实施基于气体的MPD阅读器，以增强P芯片（P芯片/MPD）。 然而，对生物医学界来说，更重要的是新探测器的使能特性。它将使一个专有的系统，用于研究蛋白质-蛋白质相互作用，其灵敏度比目前的技术高出数百倍。这种蛋白质-蛋白质相互作用定量系统利用MPD的精密仪器灵敏度，即使对于低丰度蛋白质也能实现最高灵敏度检测和合理的通量。超高的灵敏度和非常大的动态范围结合联合收割机，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的上级。这个过程的特殊性质允许估计从“供体”到“受体”分子的距离。在另一个实施方案中，其允许阐明特定大分子的完整性和拓扑构型。使用适当的底物，其允许非常特异性地测量通过适当的酶对靶大分子的切割。 该提案中提出的最重要的发展要素是创新的基于气体的电子检测器，它允许在方便的96井格式同时测量许多蛋白质的相互作用。它基于对气体中电子的检测，需要广泛的电子和软件开发。

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.