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，情况可能会恶化。不是病人，不是医生，当然也不是保险公司对慢性病的护理和患者结果的复杂性感到满意。然而，随着糖尿病患者广泛使用可穿戴式血糖监测仪，慢性疾病的护理无疑得到了改善。持续的可穿戴监测对心脏病和糖尿病的影响是如此巨大，以至于已经出现了商业上出现的长期植入式血糖和心脏功能监测仪。然而，由于传感器必须持续一年或更长时间的连续运行的极端困难的要求，植入式传感器只有少量的措施是可能的。这是不幸的，因为植入式监护仪理论上可以降低成本(减少到医生办公室进行测试的次数)，通过更及时和可操作的数据改善患者的预后，并且凭借其简单性(几乎不需要用户的努力)对患者的生活方式选择产生更大的影响。因此，需要一种新技术，不仅可以测量体内多种类型的分子，而且可以可靠地运行一年或更长时间，从而使植入性使用变得实用和可取。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件，从而实现第一个可推广到多种慢性病的植入式监测平台。该项目工作计划的重点是适配子传感器，它将DNA链放置在电极上，DNA捕获并允许对全身循环的分子进行电子测量。这些适配子传感器基本上提供了与在医生办公室进行血液测试所获得的相同类型的信息，但将在体内始终进行测量。使这些传感器持续足够长的时间进行植入操作是一个重大挑战，也是该项目的具体科学重点。为了实现一年以上的运行，该项目将使用坚固的多孔氧化物稳定传感器表面，目标是实现1个月的可靠运行，然后开发具有12个传感器的设备设计，这些传感器在体内以一个月的间隔顺序暴露，从而实现至少12个月的运行。实现12个月的手术为植入传感器打开了可能性，患者和医生可以持续获得健康状态，并以更简单、更有效的方式管理患者的慢性病。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.