Needle-implantable sensor with multi-sensing elements for accurate glucose monitoring

 描述(申请人提供)：在过去的五年里，Biorasis，Inc.一直在开发一种完全可植入的生物传感器平台(0.5x0.5x5 mm)，能够连续监测血糖。开发这种微型化传感器的基本原理取决于利用光作为动力源和通信链路的极端微型化。这种植入物尺寸的缩小导致在植入过程中对组织的损害最小。各种组织反应调节剂的局部释放也提供了长期传感器功能所需的有效的炎症控制和纤维化抑制。该平台的传感元件基于新颖的5层器件架构，在选择性、线性度、响应时间和灵敏度方面具有高性能。体内研究表明，在14天的时间里，我们的传感器测量的血糖水平与参考标准之间的总平均绝对相对差异(MARD)值为11-13%。虽然这已经可以与目前市场上的经皮传感器相媲美，但我们的分析表明，如果考虑到传感器元件内对影响葡萄糖扩散的通透性变化的可变性，传感器的MARD值可以进一步降低到5-6% 和其他共基质。目的/假设：将葡萄糖敏感元件对葡萄糖和其他共基质渗透性变化的反应关联起来，可以显著提高传感器在较长时间内(3个月)对低血糖和高血糖区域的准确度(MARD值降至5-6%)。研究设计：这项第一阶段的研究将集中于在正常和糖尿病大鼠身上进行为期1个月的全集成设备的概念验证演示。为此，我们目前的原型设备将配备一个新的电子芯片，包括两个额外的恒电位器和传感器选择电路，以及三个传感元件。此外，还将进行微电子/光电子元件和传感元件的晶片级集成和封装，以进行体内研究和验证。相关性：鉴于全球糖尿病患者数量的不断增加，对能够准确检测血糖水平的设备有巨大的需求。与使用非侵入性方法监测血糖相关的困难不同，完全可植入的设备的极端微型化以及保证的准确性和长期操作提供了一种可行的替代方案。拟议的多传感元件平台解决了小型化和准确的血糖读数问题。此外，无线通信和延长使用寿命使其成为糖尿病护理的有效设备，以及在临床前动物研究中监测代谢物的强大工具。

 DESCRIPTION (provided by applicant): Over the past five years, Biorasis, Inc. has been developing a totally implantable biosensor platform (0.5 x 0.5 x 5 mm) capable of continuously monitoring glucose. The underlying principle in developing this miniaturized sensor hinges on extreme miniaturization utilizing light, both as a powering source and a communication link. Such implant size reduction results in minimal tissue damage during implantation. The localized release of various tissue response modifiers has also afforded effective inflammation control and fibrosis suppression, needed for long-term sensor functionality. The sensing element of this platform is based on a novel 5-layer device architecture that yields high performance in terms of selectivity, linearity, response time and sensitivity. In vivo studies have indicated an aggregate mean absolute relative difference (MARD) value of 11-13% between our sensor-measured glucose levels and reference standards over a period of 14- days. While this is already comparable to the transcutaneous sensors currently in market, our analysis has shown that the sensor MARD values can be further lowered to 5-6% if one takes into consideration the variability within the sensing element to permeability changes that affect the diffusion of glucose and other co- substrates. Objective/Hypothesis: Correlating the response of the glucose sensing element to the permeability changes for glucose and other co-substrates, can substantially improve sensor accuracy (with MARD values down to 5- 6%) for both hypo- and hyperglycemic regions over extended periods of time (3 months). Study Design: This Phase I study will be focused on proof-of-concept demonstration of the fully-integrated device for 1-month in normal and diabetic rats. For this, our current prototype device will be outfitted with a new electronic chip comprising of two additional potentiostats and sensor-select circuitry, along with the three sensing elements. Furthermore, wafer-level integration and packaging of the micro-/optoelectronic components and sensing elements will be carried out for in vivo studies and validation. Relevance: In view of the growing number of diabetics worldwide, there is a tremendous need for devices that provide accurate detection of glucose levels. In lieu of the difficulties associated with glucose monitoring using non-invasive methods, extreme miniaturization of a totally implantable device together with assured accuracy and long-term operation, present a viable alternative. The proposed multi-sensing element platform addresses miniaturization and accurate glucose readings. In addition, the wireless communication and prolonged lifetime render it an effective device for diabetic care as well as a powerful tool for metabolite monitoring in pre-clinical animal research.