Charge sensitive optical detection for high throughput study of small molecules

描述（由申请人提供）：涉及小分子生物化学反应的小分子和翻译后蛋白质修饰的高通量检测对于理解癌症发生和进展的潜在机制、发现能够进行早期癌症检测的适当生物标志物以及筛选有效癌症治疗的候选药物至关重要。最广泛使用的技术使用荧光标记，这对于尺寸与荧光染料相当的小分子来说是有问题的。已经开发了各种无标记技术，但它们的灵敏度随着分子的大小而降低，使得检测小分子极具挑战性。为了满足这一需求，本项目将开发电荷敏感光学检测器。该技术特别适用于检测小分子和涉及小质量变化的生化相互作用。该检测方法使用与标准微孔板技术兼容的光学探针，使其对于高通量检测具有吸引力。该项目的成功将导致一种新的检测技术来测量小分子相互作用，如药物-靶标相互作用，膜蛋白信号传导，蛋白质磷酸化和其他翻译后修饰，涉及电荷转移的氧化和还原反应。其中许多过程对于癌症的研究、诊断和治疗非常重要。 公共卫生相关性：一种新的电荷敏感光学检测技术将被开发用于小分子相互作用的无标记测量。该项目的成功将为包括癌症在内的疾病的研究、诊断和治疗带来一种新的高通量筛选工具。

DESCRIPTION (provided by applicant): High-throughput detection of small molecules and post translational protein modifications that involve small molecule biochemical reactions are critical for understanding the mechanisms underlying cancer initiation and progression, for discovering proper biomarkers that enable early cancer detection, and for screening drug candidates for effective cancer treatment. The most widely used technology uses fluorescence labels, which is problematic for small molecules whose sizes are comparable to those of the fluorescent dyes. Various label- free techniques have been developed, but their sensitivity diminishes with the size of the molecules, making it extremely challenging to detect small molecules. To address the need, a charge sensitive optical detection will be developed in this project. The technology is particularly suitable for the detection of small molecules, and biochemical interactions that involve small mass changes. The detection method uses optical probes that compatible with the standard microplate technology, making it attractive for high-throughput detection. The success of the project will lead to a new detection technology to measure small molecule interactions, such as drug-target interactions, membrane protein signaling, protein phosphorylation and other post translational modifications, oxidative and reduction reactions that involves charge transfer. Many of these processes are highly important for the research, diagnostic and treatment of cancer. PUBLIC HEALTH RELEVANCE: A new charge sensitive optical detection technology will be developed for label-free measurement of small molecule interactions. The success of the project will lead to a new high-throughput screening tool for research, diagnostic and treatment of diseases including cancer.