An Implantable Biosensor Platform Enabled by Novel Porous Oxide Protection of Electrochemical Aptamer Working Electrodes

在美国，管理慢性病是医疗保健系统的最大成本，而且随着人口老龄化，这种情况将会恶化。没有病人，没有医生，当然也没有保险公司对慢性疾病治疗的复杂性和病人的结果感到满意。然而，随着可穿戴式血糖监测在糖尿病患者中的广泛应用，慢性病护理的改善毫无疑问已经实现。持续的可穿戴式监测对心脏病和糖尿病的影响是如此巨大，以至于已经出现了一种用于监测血糖和心脏功能的长效植入式监测设备。然而，由于传感器必须持续一年或更长时间的连续运行，因此只有少数措施可以使用植入式传感器。这是不幸的，因为从理论上讲，植入式监测器可以降低成本（减少到医生办公室进行检查的次数），通过更及时和可操作的数据改善患者的结果，并且由于它们的简单性（几乎不需要用户的努力）对患者的生活方式选择有更大的影响。因此，我们需要一种新技术，它不仅能测量体内多种类型的分子，而且能在一年或更长时间内可靠地运行，从而使植入式应用变得实用和可取。该项目的具体目标是展示分子传感器在体内监测多年所需的基本构建模块，从而实现首个可推广到多种慢性疾病的植入式监测平台。该项目的工作计划集中在适体传感器上，它将DNA链放在电极上，DNA捕获并允许电子测量在全身循环的分子。从本质上讲，这些适体传感器提供的信息与医生办公室的血液检查相同，但它们将一直测量体内的情况。使这些传感器持续足够长的时间用于植入手术是一个主要的挑战，也是这个项目的具体科学重点。为了实现一年以上的运行，该项目将用坚固的多孔氧化物稳定传感器表面，目标是1个月的可靠运行，然后开发一种带有12个传感器的设备设计，这些传感器每隔一个月在体内暴露一次，这样至少可以运行12个月。实现12个月的手术为植入传感器提供了可能，患者和医生可以持续获取健康状况，并以更简单、更有效的方式管理患者的慢性疾病。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。

Managing chronic diseases in the United States is the biggest cost to the health care system and is poised to worsen as the population ages. Not patients, not doctors, and certainly not insurance companies are satisfied with the complexity of care and patient outcomes for chronic diseases. However, improved care in chronic disease has without question been achieved with the wide-spread use of wearable monitoring of glucose for diabetics. The impact of continuous wearable monitoring has been so substantial for heart disease and for diabetes that there is already a commercial emergence of long-lasting implantable monitors for glucose and heart function. However, only a small number of measures are possible with implantable sensors due to the ultra-difficult requirement of the sensors having to last a year or more of continuous operation. This is unfortunate, because implanted monitors can in theory reduce costs (less trips to the doctor’s office for tests), improve patient outcomes by more timely and actionable data, and by virtue of their simplicity (almost no user effort) have greater impact on patient lifestyle choices. A need therefore exists for a new technology that can not only measure many types of molecules in the body, but do so with reliable operation for a year or more such that implantable use becomes practical and desirable.The specific objective of this project is to demonstrate the fundamental building blocks needed for molecular sensors to monitor inside the body for multiple years, and therefore enable the first ever implantable monitoring platform that is generalizable to multiple chronic diseases. The project work plan focuses on aptamer sensors, which place strands of DNA on an electrode, and the DNA captures and allows electronic measurement of molecules circulating throughout the body. These aptamer sensors essentially provide the same type of information achieved with a blood test at the doctor’s office, but instead will be measuring all the time inside the body. Making these sensors last long enough for implanted operation is a major challenge and is the specific scientific focus of this project. To enable more than one year of operation this project will stabilize the sensor surface with robust porous oxides with a goal of 1 month of reliable operation, then develop a device design with 12 sensors that are sequentially exposed at one-month intervals inside the body such that at least 12 months of operation is achieved. Achieving 12-month operation then opens the possibility for an implanted sensor, where patients and doctors have continuous access to health status and a simpler and more impactful way to manage a patient’s chronic disease.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.