Real-time biosensor for mapping the function of the pancreas

用于绘制胰腺功能的实时生物传感器

• 批准号: 10170068
• 负责人: HYONGSOK Tom SOH
• 金额: $ 145.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170068
• 关键词: Animals; Area; Binding; Biological Assay; Biological Markers; Biosensor; Biotechnology; Communication; Communities; Data; Development; Development Plans; Devices; Diabetes Mellitus; Electronics; Equilibrium; Feedback; Generations; Glucagon; Glucose; Goals; Hormones; Insulin; Kinetics; Light; Maps; Measurement; Measures; Molecular Biology; Molecular Conformation; Mus; Neuromodulator; Organ; Organ Model; Pancreas; Performance; Peripheral Nerve Stimulation; Pharmaceutical Preparations; Physiological; Play; Process; Production; Research; Research Personnel; Resolution; Role; Signal Transduction; Source; System; Technology; Testing; Therapeutic; Time; Universities; aptamer; blood glucose regulation; chemical group; cytokine; in vitro testing; in vivo; in vivo evaluation; insight; interest; programs; prototype; scale up; screening; sensor; small molecule; temporal measurement

Project Summary: The capability to manipulate pancreatic function through peripheral nerve stimulation offers exciting therapeutic potential, but will require a deeper understanding of underlying molecular biology as well as inter-organ signaling and communication. Such processes are difficult to study in vivo because they occur on time-scales of seconds to minutes—far faster than can be measured by conventional assays. The primary goal of this project is to develop real-time in vivo biosensors that can continuously measure the physiological concentrations of glucose, insulin and glucagon in specific areas of the pancreas of freely moving animals. Our biosensors will detect these three biomarkers with high sensitivity (pM~nM), spatial resolution (~10 μm) and temporal resolution (~1 minute), and thereby offer unprecedented insights into the molecular biology of the pancreas. We will be building upon aptamer biosensor technology previously developed by our group, with which we have already demonstrated the first continuous measurement of small molecule drugs in vivo as well as closed-loop feedback control in live animals. This is a “platform” technology that can be readily adapted to measure a wide range of biomarkers by swapping the aptamer probes, as we have demonstrated previously. Upon successful development of this real-time biosensor for the pancreas, we will expand the range of targets to 20 other biomarkers, including neuromodulators and cytokines that play important roles in peripheral nerve stimulation. To make these biosensor systems available to other researchers, a startup company (RT Biotech) will refine the prototypes and produce them at low volumes for other groups within the SPARC program within 3 years.

项目摘要：通过周围神经刺激来操纵胰腺功能的能力提供了 令人兴奋的治疗潜力，但需要更深入地了解潜在的分子生物学以及 器官间信号和通信。这样的过程很难在体内研究，因为它们发生在 时间刻度从几秒到几分钟--远远快于传统的检测方法。首要目标 该项目的重点是开发实时在体生物传感器，这种传感器可以连续测量生理 自由活动动物胰腺特定区域的葡萄糖、胰岛素和胰高血糖素浓度。我们的 生物传感器将以高灵敏度(PM~NM)、空间分辨率(~10μm)和 时间分辨率(~1分钟)，从而提供了前所未有的洞察力 胰腺。我们将建立在我们团队以前开发的适体生物传感器技术的基础上，通过 我们已经展示了第一个在体内连续测量小分子药物以及 活体动物的闭环反馈控制。这是一种“平台”技术，可以很容易地适应 通过交换适体探针来测量广泛的生物标记物，正如我们之前所演示的那样。 在成功开发这种胰腺实时生物传感器后，我们将扩大靶标的范围 至20个其他生物标志物，包括在周围神经中发挥重要作用的神经调节剂和细胞因子 刺激。为了使这些生物传感器系统可供其他研究人员使用，一家初创公司(RT Biotech) 将改进原型，并在3年内为SPARC计划内的其他小组小批量生产它们 好几年了。