An Injectable Glucose Biosensor Based on a Self-cleaning Membrane & NIR FRET Assay

糖尿病影响着美国数以百万计的人。为了避免严重的健康风险，必须测量血糖并将其保持在正常水平。连续的血糖监测仪被用来取代手指刺痛试验。这使得白天和晚上都可以测量血糖水平。目前的连续血糖监测仪使用一个小的传感器探头，就像插入皮肤的电线一样。通常放在手臂上，大约每两周更换一次。传感器上方的皮肤上放置了一个发射器，用于与智能手机通信。这项研究旨在开发一种更容易使用的糖传感器。传感器将是一粒大米的大小。这种小尺寸允许用针将其注射到手腕的组织中。然后，可以使用手表之类的设备轻松地监测血糖水平。这种新的传感器预计将使用30天或更长时间。它会像电流传感器一样对糖的变化很敏感。它的使用也会很方便。本研究也将为高中生和大学生提供培训经验。该项目旨在开发一种米粒大小的可注射葡萄糖生物传感器，使其能够通过可穿戴设备进行连续监测。这将通过分别通过创新的生物材料和分析化学来解决与生物兼容性和光学葡萄糖传感相关的挑战来实现。科学目标包括：(1)开发一种由自清洁膜和近红外(NIR)荧光葡萄糖传感分析组成的可注射生物传感器，并用自闭帽将该分析封闭在膜的中央空腔内。(2)开发一种可穿戴的光学检测系统来询问生物传感器并测量血糖水平(由LED和光电二极管对组成，不需要固定的发射器)。(3)评估生物传感器监测体内葡萄糖水平的能力(大鼠模型)，以及膜减少异物反应(FBR)的能力。除了允许非手术注射外，这种生物传感器设计还提供了方便、非侵入性的检测，仅使用类似手表的设备。近红外荧光光学传感预计将能够对所有肤色和体重指数(BMI)的个人进行血糖检测。这项工作的结果将对其他植入式生物传感器和设备的开发产生广泛的影响。自清洁膜将提高人们对主动机制而不是被动机制在生物污染控制中的作用的认识，从而改善生物相容性。近红外荧光分析将促进光学传感方法的知识，这些方法实现了非凡的体外稳定性、可逆性、动态范围和灵敏度。该奖项反映了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。

Diabetes affects millions of people in the United States. To avoid serious health risks, blood sugar must be measured and kept at normal levels. Continuous blood sugar monitors are used to replace finger prick tests. This allows measurement of sugar levels both day and night. Current continuous sugar monitors use a small sensor probe like a wire that is inserted through the skin. This is usually put in the arm and is replaced about every two weeks. A transmitter is put on the skin over the sensor to communicate to a smartphone. This research seeks to develop a sugar sensor that is easier to use. The sensor will be the size of a grain of rice. This small size allows it to be injected into the tissue of the wrist with a needle. Then the sugar levels can be comfortably monitored with a device like a watch. This new sensor is expected to last 30 days or more. It will be sensitive to the change in the sugar like current sensors. It will also be convenient to use. This research will also provide training experiences to high school students and university students. This project seeks to develop a grain-of-rice size, injectable glucose biosensor to enable continuous monitoring with a wearable device. This will be accomplished by addressing challenges related to biocompatibility and optical glucose sensing through innovative biomaterials and assay chemistries, respectively. The scientific objectives include: (1) Develop an injectable biosensor comprised of a self-cleaning membrane and a near-infrared (NIR) fluorescence glucose sensing assay and sealing the assay within the membrane’s central cavity with self-closing caps. (2) Develop a wearable optical detection system to interrogate the biosensor and measure glucose levels (comprised of an LED and photodiode pair, without the need for an affixed transmitter). (3) Assess the biosensor’s ability to monitor glucose levels in vivo (rat model), as well as the membrane’s reduction of the foreign body reaction (FBR). Beyond allowing non-surgical injection, such a biosensor design affords convenient, non-invasive detection exclusively with a watch-like device The NIR fluorescence optical sensing is expected to enable glucose detection for individuals of all skin tones and body mass indices (BMIs). The results of this work are poised to have broad impact in the development of other implantable biosensors and devices. The self-cleaning membrane will advance knowledge in the role of active mechanisms rather than passive mechanisms for biofouling control, and hence improved biocompatibility. The NIR fluorescence assay will advance the knowledge of optical sensing methods that achieve exceptional in vitro stability, reversibility, dynamic range, and sensitivity.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.