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

目前，对于首次或复发性上皮性卵巢癌，尚无可靠的早期诊断方法。本项目将开发一种新的微管热成像技术，如果成功，将为癌症进展机制、早期癌症检测和早期癌症诊断提供新的见解。本研究提出，特定的细胞类型具有对热的特征反应，可用于识别细胞类型。这种特性的表征可能会为正常或病变细胞引入一类新的细胞热标志物。显著的更广泛的影响包括培训和指导研究生，本科生和高中生在热科学。这将通过纳米和生物工程项目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生命过程的信息。目前的项目目标是：(1)确定浆液上皮性卵巢癌进展细胞系面板的热特性。准备一个上皮性卵巢癌的3D模型作为实验平台。微传感器和伴随的热导率和热扩散率技术方法将用于临床相关浆液上皮卵巢癌细胞系；(2)将热表征谱与增殖表征谱相关联，作为上皮性卵巢癌的过渡预测模型。热探针细胞的后续分析将使用荧光分析来确定reazurin检测的增殖。将进行线性回归分析，以确定热表征和增殖表征是否与癌症转移相关。值得注意的是，新的热特性可以取代当前强调依赖广泛的基因组和蛋白质组学分析的范式。此外，该项目的附加价值是识别（并继续探究以了解）细胞固有的热性能。该技术和方法如果成功，将成为一种非侵入性的工具，可以更快地诊断上皮性卵巢癌，并加快下一步生物标本的测定，以便对方法和技术进行早期验证。事实上，这项对热力学细胞特性的实证研究将推进最近提出的传热在代谢重编程、生物能量学和氧化还原代谢状态中在癌细胞存活中的作用理论。这种新发现将为新疗法打开大门。此外，未来在有问题的细胞位置进行实时诊断，当与腹腔镜检查相结合时，可能会导致早期发现和诊断。表面上看，这项技术将扩展到其他循环血液肿瘤和疾病模型，为癌症检测和治疗解决方案提供未来的进步。代表性不足的学生将成为北德克萨斯大学麦克奈尔学者项目、国家科学基金会本科生研究经验项目的首选新兵。德克萨斯州数学与科学学院的高中课程也将包括在内。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.