Implantable biosensors for real-time in vivo interrogation of biological phenomena

Sayler1159344这项研究致力于将发光(生物发光)人体细胞系与集成电路微发光仪相结合，以创建用于动物生理内部监测的微型、可植入的生物传感接口。传统的成像技术依靠外部摄像机来穿透和识别嵌入在小动物受试者体内的发光细胞特征。不幸的是，由于吸收、衰减和散射，即使是最灵敏的超冷相机也无法探测到活组织中几厘米深以外的光信号。如果不在工程细胞的成像硬件灵敏度和/或光信号发射强度方面取得重大进展，承诺实时、非侵入性地可视化小动物健康状况的生物成像应用可能永远不会实现在大型动物(即人类)中成像、跟踪和诊断疾病的变革性飞跃。据推测，内部成像可能比外部成像更可行和实用，能够检测来自工程人类细胞的光的植入式光学芯片的生物工程可能是有效的全身成像的解决方案。这项研究的学术价值是一种变革性的新成像技术，它使我们更接近生物传感战略，朝着自主感知和响应的人类生物疗法发展，在这种生物疗法中，疾病状态被自动识别和治疗，其结果允许实时和远程的患者与医生的关系，并以极大的降低成本实现个性化医疗和疾病护理管理的转变。更广泛的影响包括博士后培训和本科生融入研究项目，生命科学和工程学科之间的多学科合作，研究成果的广泛传播，以及以K-12科学、技术、工程和数学(STEM)倡议为中心的外展努力。

Sayler1159344This research effort is focused on the merging of light-emitting (bioluminescent) human cell lines with integrated circuit microluminometers to create miniaturized, implantable biosensing interfaces for internal monitoring of animal physiology. Conventional imaging technology relies on external cameras to penetrate and identify light-emitting cellular signatures embedded within small animal subjects. Unfortunately, due to absorption, attenuation, and scattering, even the most sensitive ultracooled cameras are unable to detect light signals beyond depths of a few centimeters in living tissue. Without major advances in imaging hardware sensitivity and/or light signal emission strength of engineered implanted cells, bioimaging applications that promise real-time, noninvasive visualization of health status in small animals may never achieve the transformational leap towards imaging, tracking, and diagnosing diseases in larger animals (i.e., humans). It is hypothesized that it may be more feasible and practical to image internally rather than externally, and that the bioengineering of an implantable optical chip capable of detecting light from engineered human cells tuned to human disease states may be a solution for effective whole-body human imaging. The intellectual merit of this research is a transformative new imaging technology that brings us closer to biosensing strategies evolved towards autonomous sense-and-respond human biotherapies where disease states are automatically recognized and treated, the outcome of which permits real-time and remote patient to doctor relationships and transformations in personalized medicine and disease care management at greatly reduced costs. Broader impacts include postdoctoral training and integration of undergraduate students within the research project, multidisciplinary collaborations between the life sciences and engineering disciplines, broad dissemination of research results, and outreach efforts centered on K-12 Science, Technology, Engineering & Mathematics (STEM) initiatives.