Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Profusa, Inc., South San Francisco, CA, USA.
J Diabetes Sci Technol. 2020 Mar;14(2):204-211. doi: 10.1177/1932296819886928. Epub 2019 Nov 9.
Continuous glucose monitors (CGMs) enable people with diabetes to proactively manage their blood glucose and reduce the risk of hypoglycemia. Commercially available CGMs utilize percutaneous electrodes that, after days to weeks of implantation, are subjected to the foreign body response that severely reduces sensor accuracy. The previous work demonstrated the use of hydrogels containing a glucose-responsive viologen that quenches a nearby fluorophore. Here, we investigate the immobilization of this sensing motif onto a nanoparticle surface and optimize local surface concentrations for optical glucose sensing.
A viologen quencher-fluorescent dye system was incorporated into poly(2-hydroethyl methacrylate) hydrogels in varying quantities to assess the effect of quencher-fluorophore concentration on glucose responsiveness. The sensing motif was then immobilized onto silica nanoparticles by carbodiimide chemistry. Nanosensors with a range of dye and quencher concentrations were challenged for glucose responsiveness to determine the optimal sensor formulation.
When incorporated into a hydrogel, high concentrations of viologen quencher and fluorophore were required to permit electron transfer between the two components and yield a detectable glucose response. Immobilization of this glucose-responsive system onto a silica nanoparticle facilitated this electron transfer to yield detectable responses at even low concentrations. Increasing quencher concentration on the nanoparticle, relative to the fluorophore, resulted in the greatest apparent glucose response.
The nanoparticle sensors demonstrated excellent glucose response in the physiological range and are a promising tool for real-time glucose tracking.
连续血糖监测仪（CGM）使糖尿病患者能够主动管理血糖，降低低血糖风险。市售的 CGM 使用经皮电极，在植入几天后到几周后，会发生异物反应，严重降低传感器的准确性。之前的工作已经证明了使用含有葡萄糖响应型紫罗碱的水凝胶的方法，该紫罗碱可以猝灭附近的荧光团。在这里，我们研究了将这种传感基序固定在纳米粒子表面上，并优化用于光学葡萄糖传感的局部表面浓度。
将紫罗碱猝灭剂-荧光染料系统以不同的量掺入聚（2-羟乙基甲基丙烯酸酯）水凝胶中，以评估猝灭剂-荧光团浓度对葡萄糖响应性的影响。然后通过碳二亚胺化学将传感基序固定在二氧化硅纳米粒子上。用一系列染料和猝灭剂浓度挑战纳米传感器以测试其葡萄糖响应性，以确定最佳传感器配方。
当掺入水凝胶中时，需要高浓度的紫罗碱猝灭剂和荧光团才能允许两个组件之间的电子转移，并产生可检测的葡萄糖响应。将这种葡萄糖响应系统固定在二氧化硅纳米粒子上，即使在低浓度下也可以促进这种电子转移，从而产生可检测的响应。与荧光团相比，纳米粒子上猝灭剂浓度的增加导致了最大的表观葡萄糖响应。
纳米粒子传感器在生理范围内表现出出色的葡萄糖响应，是实时葡萄糖跟踪的有前途的工具。
