CAREER: Biosensing in thermal space

虽然已经发现了许多对癌症具有一定特异性的生物标志物，但由于缺乏肿瘤特异性，显然没有一种生物标志物能够理想地区分致死性癌症和惰性癌症。在寻找更具体的生物标志物的同时，一种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，由于峰值重叠、缺乏探针特异性或读出系统的复杂性，现有技术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，该方法将设计、生产一系列具有尖锐和离散熔融峰的固液相变材料（金属和共晶合金）的成分编码纳米颗粒，并用一系列配体进行修饰，并用于多种生物标志物的体外检测。一种生物标志物和一种纳米颗粒之间将建立一对一的对应关系。每个生物标志物的存在和浓度将由相应纳米颗粒的熔化峰和熔化焓得出。多重结果将用于使用模式识别方法在早期阶段区分致命癌症。知识优势：热生物传感利用了一个众所周知的，但尚未开发的固体热现象：固体的温度不会超过其熔点，直到整个固体融化，金属或共晶合金在线性热扫描时具有成分依赖的熔点和尖锐的熔点。热生物传感技术将过去的相图知识与纳米颗粒的尺寸优势独特地结合起来，在生物标志物检测中具有独特的特点。通过填补生物传感、冶金和纳米技术之间的知识空白，使用相变纳米颗粒的热生物传感代表了从现有的电、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方面的技术突破。致命癌症的早期发现将提高患者的生存能力，降低诊断和治疗费用，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。热生物传感也可以扩展到各种应用，包括生物医学，食品生产和加工，以及多种细菌，病毒和生物毒素的快速检测，用于生物安全，生物战防御和环境应用。该教育计划的目标是吸引学生进入生物纳米工程领域，并通过启发年轻人的思想对学生产生持久的影响，并通过保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.