Plasmonic optophysiology

生物分析科学的下一个前沿领域之一需要设计能够提供区分健康和疾病组织的分子变化的完整图像的传感器。这种化学传感装置需要解锁疾病起源的特定分子机制，调查治疗对组织的影响，并最终可能为监测治疗进展或诊断疾病提供分子内窥镜。植入组织的分子传感器将使分析化学以及最终的生命科学实现重大飞跃。这是我研究计划中心面临的下一个挑战。等离子体光生理学这一新兴领域将光子器件的概念应用于在细胞或组织的分子水平上测量生理参数。DG的主要目标是设计基于细胞和组织中工作的(局域化)表面等离子体共振(SPR或LSPR)的分析传感器。这笔赠款将用于建立等离子体光学生理学的分析、材料和光学基础。具体地说，我们将构建基于LSPR和嵌入在光纤上的经典SPR的新型传感器。我们将研究放置在纳米纤维上的纳米颗粒的消光(反射/透射谱)或散射(暗场光谱)特性，因为它以前没有被研究过用于等离子体传感。然后，折射率传感器将通过使用分子捕捉剂的纳米颗粒的功能化来构建，这将导致能够检测生物分子(如核酸、肽或蛋白质)的空间可寻址的微观等离子体传感器。我们将构建在细胞和组织中进行等离子体光生理学所需的仪器。利用模型系统，我们将验证等离子体光生理学在研究局部组织或附近培养细胞中信号肽或蛋白质表达的性能，为评估这些重要神经化学物质的分泌提供新的可能性。除了这笔赠款的范围外，我们预计血浆光学生理学最终将对药物的药理学筛选非常有用，以设计新的疗法或从现有疗法中找到最佳治疗方法，进一步推动精确医学的发展。

One of the next frontiers in bioanalytical sciences requires the design of sensors capable of providing a complete picture of the molecular changes distinguishing healthy and diseased tissues. Such chemical sensing devices are needed to unlock specific molecular mechanisms at the origin of diseases, to survey the impact of therapies on tissues and they may ultimately provide molecular endoscopes for monitoring the progress of therapies or diagnose diseases. Molecular sensors that are implantable in tissues will enable a significant leap in analytical chemistry and ultimately in life sciences. This is the next challenge at the center of my research program. The nascent field of plasmonic optophysiology applies concepts of photonic devices for the measurement of physiological parameters at the molecular level in cells or tissues. The major aim of this DG is the design analytical sensors based on (localized) surface plasmon resonance (SPR or LSPR) working in cells and tissues. This grant will serve to establish the analytical, material, and optics fundamentals for plasmonic optophysiology. Specifically, we will construct novel sensors based on LSPR and classical SPR embedded on optical nanofibers. We will investigate the extinction (reflection/transmission spectroscopy) or scattering (dark field spectroscopy) properties of nanoparticles placed on nanofibers as it has not been previously studied for plasmonic sensing. Refractometric sensors will then be constructed from the functionalization of the nanoparticle with molecular capture agents that will lead to spatially addressable microscopic plasmonic sensors capable of detecting biomolecules, such as nucleic acids, peptides or proteins. We will construct the instrumentation needed to perform plasmonic optophysiology in cells and tissues. Using model systems, we will validate the performance of plasmonic optophysiology in studying the expression of signaling peptides or proteins locally in tissues or near cultured cells, providing new possibilities to evaluate the secretion of these important neurochemicals. Extending beyond the scope of this grant, we envision that plasmonic optophysiology will ultimately be highly useful for the pharmacological screening of drugs to design new therapies or find optimal treatments from existing therapies, further advancing precision medicine.