Thermal conductivity and diffusivity of human cells as biomarkers in early-stage ovarian cancer detection

目前，尚无可靠的检测方法可用于首次或复发上皮性卵巢癌的早期诊断。该项目将开发一种新的微吸管温度成像技术，如果成功，将导致对癌症进展机制、早期癌症检测和早期癌症诊断的新见解。这项研究提出，特定的细胞类型具有对热的特征反应，可以用来识别细胞类型。对这一特性的表征可能会为正常或疾病细胞引入一类新的细胞热标记。重大的更广泛的影响包括对热学研究生、本科生和高中生的培训和指导。这将通过在纳米和生物工程项目中的实践学习经验来实现，该项目将结合不同研究领域的方法来揭示关于生命过程的信息。当前的项目目标是：(1)确定浆液性上皮性卵巢癌进展的细胞系的热特征曲线。将准备一个上皮性卵巢癌的3D模型作为试验床。微传感器和以前发表的工作中用于测量热导率和热扩散率的技术方法将被用于临床相关的浆液性卵巢癌细胞系；(2)将热特征曲线与增殖特征曲线相关联，作为上皮性卵巢癌的过渡预测模型。随后对热探针细胞的分析将使用荧光分析来确定检测到的Reazurin的增殖。将进行线性回归分析，以确定热特征曲线和增殖特征曲线是否与癌症转移相关。值得注意的是，新的热性质可以取代目前强调依赖广泛的基因组和蛋白质组分析的范式。此外，该项目的附加值是识别(并继续探索了解)细胞的固有热特性。如果成功，这项技术和方法将允许一种非侵入性工具，通过加快下一步生物标本检测来更快地诊断上皮性卵巢癌，以早期验证方法和技术。事实上，这项对细胞热力学性质的经验研究将推进最近提出的关于代谢重编程、生物能量学和氧化还原代谢状态在癌细胞生存中的热传递作用的理论。这种新的发现将为新的治疗方法打开大门。此外，未来在相关细胞位置的实时诊断，当与腹腔镜术相结合时，可能会导致早期发现和诊断。这项技术表面上将扩展到其他循环血液肿瘤和疾病模型，为未来癌症检测和治疗解决方案的进步提供依据。代表不足的学生将成为北得克萨斯大学麦克奈尔学者计划、国家科学基金会本科生研究体验计划的首选招生对象。得克萨斯数学与科学学院的高中项目也将包括在内。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Currently, there is no reliable test for early diagnosis of first time or recurrent epithelial ovarian cancers. This project will develop a new technique of micropipette thermography, which, if successful, will lead to new insights into mechanisms of cancer progression, early cancer detection, and early cancer diagnosis. This research proposes that specific cell types possess characteristic responses to heat that can be used to identify the cell type. Characterization of this property may introduce a new class of cellular thermal markers for normal or diseased cells. Significant broader impacts included the training and mentorship of graduate, undergraduate and high school students in thermal sciences. This will occur through hands-on learning experiences in the nano and bioengineering program that will combine approaches from different fields of study to reveal information about a life process.The current project objectives are: (1) to determine the thermal characterization profiles of a cell line panel of serous epithelial ovarian cancer progression. A 3D model of epithelial ovarian cancer will be prepared as a test bed. Microsensors and the accompanying technical method for both the thermal conductivity and thermal diffusivity from previous published work will be used on clinically relevant serous epithelial ovarian cancer cell lines; (2) to correlate the thermal characterization profile with the proliferation characterization profile as a Transition Prediction Model in epithelial ovarian cancer. Subsequent analysis of the thermal-probed cells will use fluorescence analysis to determine resazurin-detected proliferation. A linear regression analysis will be performed to determine whether the profiles for thermal characterization along with proliferation characterization are correlated with cancer transition. It is noted that novel thermal properties could supersede the current paradigm which emphasizes the reliance on extensive genomic and proteomic analyses. Moreover, the added value of this project is the identification of (and continued inquiry to understand) cellular inherent thermal properties. The technology and method, if successful, will allow for a non-invasive tool, faster diagnosis of epithelial ovarian cancer with expedited next step bio-specimen determinations for early validation of the method and technology. Indeed, this empirical study of thermodynamics cell properties will advance recently proposed theories of heat transfer roles in metabolic reprogramming, bioenergetics, and oxidation-reduction metabolism status in cancer cell survival. This kind of novel discovery will open doors for new therapies. Furthermore, future real-time diagnosis at the location of the cells in question, when combined with laparoscopy, may result in early detection and diagnosis. This technology ostensibly will extend to other circulating blood tumors and disease models, providing for future advancements in cancer detection and therapy solutions. Underrepresented students will be the first-choice recruits through the University of North Texas McNair Scholars Program, National Science Foundation Research Experience for Undergraduates program. Texas Academy of Mathematics and Sciences high school program will also be included.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.