CAREER: Biosensing in thermal space

1055599 SuCAREER：尽管已经鉴定出许多对癌症具有一定特异性的生物标志物，但很明显，由于缺乏肿瘤特异性，没有一种生物标志物是区分致死性癌症和惰性癌症的理想选择。与寻找更具体的生物标志物的努力并行，提供更好预测价值的可行方法是检测多种生物标志物。然而，现有技术由于峰重叠、缺乏探针特异性或读出系统的复杂性而不能用于检测大量生物标志物。本CAREER项目将研究一种新的生物传感方法，即，热生物传感，其中将设计、生产、用一系列配体修饰具有尖锐和离散熔融峰的固-液相变材料（金属和共晶合金）的一系列组合物编码纳米颗粒，并用于多种生物标志物的体外检测。将在一种类型的生物标志物和一种类型的纳米颗粒之间建立一一对应。每种生物标志物的存在和浓度将从相应纳米颗粒的熔融峰和熔融焓导出。多个结果将用于使用模式识别方法在早期阶段区分致命癌症。智力优势：热生物传感利用了一种众所周知但尚未探索的固体热现象：固体的温度不会上升到熔点以上，直到整个固体熔化，以及金属或共晶合金在线性热扫描期间具有成分相关的熔点和尖锐的熔化峰的事实。通过独特地结合过去获得的相图知识和纳米颗粒的尺寸优势，热生物传感具有用于生物标志物检测的独特特征。通过填补生物传感、冶金和纳米技术之间的知识空白，利用相变纳米颗粒的热生物传感代表了现有电、电子、磁、机械或光子系统的范式转变。更广泛的影响：热生物传感可能导致致命癌症检测和治疗的技术突破。致命癌症的早期检测将提高患者的生存能力，降低诊断和治疗成本，并通过治愈癌症和减少与癌症相关的焦虑来改善生活质量。热生物传感还可以扩展到各种应用，包括生物医学，食品生产和加工，以及用于生物安全，生物战防御和环境应用的多种细菌，病毒和生物毒素的快速检测。该教育计划旨在吸引学生进入生物纳米工程，并将通过启发年轻人的思想对学生产生持久的影响，并通过维持高素质的劳动力对社会产生持久的影响。

1055599SuCAREER: Biosensing in thermal spaceAlthough numerous biomarkers with certain specificity to cancers have been identified, it is clear that no single biomarker is ideal to distinguish lethal cancers from indolent ones due to lack of tumor specificity. Parallel to efforts of finding more specific biomarkers, a feasible way of providing better predictive value is to detect multiple biomarkers. However, existing techniques cannot be used to detect a large number of biomarkers due to peak overlapping, lack of probe-specific property or complexity of readout systems. This CAREER project will study a new biosensing method, i.e., thermal biosensing, in which a series of composition-encoded nanoparticles of solid-liquid phase change materials (metals and eutectic alloys) that have sharp and discrete melting peaks will be designed, produced, modified with a series of ligands, and used for in vitro detection of multiple biomarkers. A one-to-one correspondence will be established between one type of biomarker and one type of nanoparticles. The presence and concentration of each biomarker will be derived from the melting peak and fusion enthalpy of according nanoparticle. The multiple results will be used to distinguish lethal cancers at early stages using pattern recognition method. Intellectual Merit: Thermal biosensing uses a well-known, but unexplored thermal phenomenon of solids: the temperature of a solid will not rise above its melting point until the entire solid is molten, and the fact that metal or eutectic alloy has composition-dependent melting point and sharp melting peak during linear thermal scan. By uniquely combining phase diagram knowledge gained in the past with size advantage of nanoparticles, thermal biosensing has distinct features for biomarker detection. By filling knowledge gap among biosensing, metallurgy and nanotechnology, thermal biosensing using phase change nanoparticles represents a paradigm shift from existing electric, electronic, magnetic, mechanical or photonic systems.Broader Impact: Thermal biosensing could lead to technological breakthroughs in detection and treatment of lethal cancers. The early detections of lethal cancers will enhance survivability of patients, reduce costs of diagnosis and treatment, and improve quality of life by curing cancer and reducing anxiety associated with cancer. Thermal biosensing can also be extended to a variety of applications including biomedicine, food production and processing, and rapid detections of multiple bacteria, viruses, and biotoxins for bio-safety, bio-warfare defense and environmental applications. The educational plan is targeted to attract students into Bio-Nano engineering, and will generate lasting impacts on students by enlightening young minds, and to society by maintaining high-quality workforces.