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Administrative Supplement for Equipment: 6-axis Positioner to Improve 3D Print Quality and Print Size

设备管理补充：用于提高 3D 打印质量和打印尺寸的 6 轴定位器

基本信息

批准号：
10801667
负责人：
Troy Munro
金额：
$ 10万
依托单位：
BRIGHAM YOUNG UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-08-31
项目状态：
未结题

项目摘要

Project Summary This proposal aims to revolutionize the micro-calorimetry field by miniaturizing an adiabatic scanning calorimeter (ASC) to improve the accuracy of thermodynamic data of protein unfolding. Unlike the thousands of existing microscopic-DSCs (differential scanning calorimeters), a micro- ASC does not have to sacrifice accuracy for sensitivity during phase transitions, and actually improves in accuracy as the scan approaches a phase transition. This is particularly important as micro-calorimetry is the gold standard to provide experimental measurements of enthalpy, binding affinity, and heat capacity to calculate the entropy and Gibbs energy of protein structural changes. The significance of the proposed work is it will produce a suite of tools that can increase the pace of pharmacological and biological chemistry discoveries, by understanding the fundamental role thermodynamics has in disease occurrence, diagnosis, and treatment. Recent advancements in 3D printing of microfluidic devices can remove the roadblocks that have prevented taking advantage of ASC’s benefits when studying protein folding/unfolding and stability. Aim 1 will build on our previous experience with both 3D printing and injecting liquid materials to improve the capabilities of microfluidic devices by making micro-ASC devices. We will design a series of printed calorimeter sections using our custom digital light project stereolithography (DLP-SL) 3D printer. Each printed section can then be modified after printing to achieve a different function, including but not being limited to: (1) casting molds to make metallic enclosures, a thermoelectric generator composed of injectable materials, and (3) low thermal conductivity aerogel impregnated resins. Then, because the printer can print internal features as small as 7𝜇𝑚, we can make sure each section has a barb and a mating receptor to allow the different printed sections to be assembled together into a calorimeter. Aim 2 will use these functionalized sections to create the adiabatic conditions, low thermal conductance, low thermal noise, and high sensitivities needed for both a micro-ASC and a micro-ITC (isothermal titration calorimeter) on the same microfluidic platform. Aim 3 will use the micro-ASC/ITC devices to measure the unfolding dynamics of two amyloid proteins, amyloid-𝛽 (A𝛽) and lysozyme. This will show that the technology is suitable for improved thermodynamic measurements and can be applied to other protein systems. The overall objective of this study is develop a series of devices that can be widely accessible, and then use those tools to measure the fundamental thermodynamic behavior that dictates the stability of key amyloid proteins that can cause disease.

项目摘要该提案旨在通过将绝热的微热量测量方法应用于微热量测量领域，扫描量热仪（ASC），以提高蛋白质去折叠的热力学数据的准确性。与现有的数千种显微DSC（差示扫描量热仪）不同， ASC在相变期间不必牺牲灵敏度的准确性，实际上随着扫描接近相变，精度提高。这一点尤其重要，因为微量量热法是提供焓、结合、结合和/或结合的实验测量的黄金标准。亲和力和热容来计算蛋白质结构变化的熵和吉布斯能。这项工作的重要性在于，它将产生一套工具，药理学和生物化学的发现，通过了解热力学在疾病发生、诊断和治疗中的作用。微流体设备3D打印的最新进展可以消除在研究蛋白质折叠/解折叠时，稳定Aim 1将建立在我们之前在3D打印和注射液体方面的经验基础上材料，以通过制造微ASC装置来改善微流体装置的能力。我们我将设计一系列印刷热量计部分使用我们的定制数字光项目立体光刻（DLP-SL）3D打印机。每个打印部分可以在打印后进行修改以实现不同的功能，包括但不限于：（1）铸造模具，以使金属外壳，由可注射材料组成的热电发电机，以及（3）低热导电气凝胶浸渍树脂。然后，由于打印机可以将内部特征打印为小到7厘米，我们可以确保每个部分都有一个倒钩和一个交配受体，不同的打印部分组装成一个热量计。目标2将使用这些功能化的部分，以创建绝热条件，低热导率，低热噪声，以及微型ASC和微型ITC（等温滴定）所需的高灵敏度量热计）在相同的微流体平台上。Aim 3将使用微型ASC/ITC设备，测量两种淀粉样蛋白，淀粉样蛋白酶（Aβ）和溶菌酶的解折叠动力学。𝛽这将表明该技术适用于改进的热力学测量，适用于其他蛋白质系统。本研究的总体目标是开发一系列设备可以被广泛使用，然后使用这些工具来测量基本的热力学行为决定了可能导致疾病的关键淀粉样蛋白的稳定性。