• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Single photon counting for ultra-weak fluorescence detection: System design, characterization and application to DNA-sequencing.
【24h】

Single photon counting for ultra-weak fluorescence detection: System design, characterization and application to DNA-sequencing.

机译：用于超弱荧光检测的单光子计数：系统设计，表征和在DNA测序中的应用。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The objective of the proposed research is to design and characterize single photon counting systems (SPCSs) for detecting ultra-weak fluorescent signals in various biomedical applications, our application being DNA-sequencing. This thesis investigates the feasibility of designing cost-effective, SPCSs to perform fast, high performance DNA-sequencing at low cost.;Recently solid-state alternative to the traditional photomultiplier tube (PMT) called silicon photomultiplier (SiPM) became commercially available. SiPMs are analog detectors (output signal proportional to number of input photons) that are primarily used in applications in fields such as nuclear physics, nuclear medicine etc., where the incoming photons usually arrive simultaneously in few numbers. SiPM is designed using standard CMOS technology and offer exciting advantages, but it is not used in photon counting applications as digital detectors, mainly due to their high dark count rate (DCR). This thesis investigates the photon counting properties of SiPM and demonstrates, for the first time, their use for detecting very weak fluorescence signals. SiPMs have high level of noise such as cross-talk and after-pulsing. This thesis investigates the noise of SiPM when used as a photon counter. Furthermore, this work demonstrates, for the first time, DNA-sequencing with SiPM, opening up a new application area, and potentially more, for this device. Multi-channel photon counting systems based on large-area SPAD (>200mum diameter) are needed in some applications, for e.g. multi-lane DNA-sequencing, but are unavailable. SiPM arrays are relatively easy to design and fabricate (CMOS), facilitating design of multi-channel photon counting systems and hence high-throughput and highly sensitive DNA-sequencing at low-cost.;This thesis presents design, development and characterization of unique single-channel and multi-channel (16 and 32 channel) SPCSs based on a large-area single photon avalanche diode (SPAD) having 0.5mm diameter (model C30902S-DTC from Perkin Elmer Optoelectronics. A novel logic circuit for generating precise quench and reset delays in the quenching circuit is presented. Further, the developed SPCSs are integrated into DNA-sequencing instruments. Excellent DNA sequencing results, demonstrating single fluorescent molecule sensitivity is presented. Thus, for the first time, experimental evidence of the application of large-area SPAD for highly sensitive detection of DNA-sequences is demonstrated.
机译：拟议研究的目的是设计和表征用于在各种生物医学应用中检测超弱荧光信号的单光子计数系统（SPCS），我们的应用是DNA测序。本文研究了设计低成本，高成本效益的SPCS来以低成本进行快速，高性能DNA测序的可行性。固态替代传统光电倍增管（PMT）的最新固态器件称为硅光电倍增管（SiPM）进入市场。 SiPM是模拟检测器（与输入光子数量成正比的输出信号），主要用于核物理，核医学等领域的应用中，其中入射光子通常同时到达几个。 SiPM是使用标准CMOS技术设计的，具有令人兴奋的优势，但由于其高暗计数率（DCR）高，因此并未在光子计数应用中用作数字检测器。本文研究了SiPM的光子计数特性，并首次证明了其在检测非常弱的荧光信号中的用途。 SiPM具有高水平的噪声，例如串扰和后脉冲。本文研究了SiPM用作光子计数器时的噪声。此外，这项工作首次证明了使用SiPM进行DNA测序，为该设备开拓了一个新的应用领域，并有可能更多。在某些应用中，例如，需要使用基于大面积SPAD（直径大于200微米）的多通道光子计数系统。多通道DNA测序，但不可用。 SiPM阵列相对易于设计和制造（CMOS），从而简化了多通道光子计数系统的设计，并因此以低成本实现了高通量和高灵敏度的DNA测序。通道和多通道（16和32通道）SPCS，基于直径为0.5mm的大面积单光子雪崩二极管（SPAD）（Perkin Elmer Optoelectronics的C30902S-DTC型）。进一步介绍了将已开发的SPCS整合到DNA测序仪中的优异DNA测序结果，证明了单个荧光分子的敏感性，从而首次证明了大面积应用的实验证据。显示了用于DNA序列高灵敏度检测的SPAD。

著录项

  • 作者

    Dhulla, Vinit H.;

  • 作者单位

    State University of New York at Stony Brook.;

  • 授予单位 State University of New York at Stony Brook.;
  • 学科 Engineering Electronics and Electrical.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 260 p.
  • 总页数 260
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号