Enabling Millimeter Scale Deeply Implanted Glucose Sensors through Ultrasonic Power Transfer and a Novel Glucose Sensing Mechanism

提案标题：通过超声能量传输实现毫米级深度植入的血糖传感器和一种新的血糖传感机制提案目标：拟议的项目的目标是实现一种新的模式，用于将能量传输到深度植入的腔内血糖监测器并与其通信。集成电路和MEMS传感技术的当前技术水平使植入传感器的立方毫米尺寸的复杂系统得以实现。然而，由于必要的电力和通信系统太大，这样的实现从未真正实现。在非常小的尺寸和大的植入深度下，通过人体组织的声能量传输从根本上比近场电磁(EM)或远场(RF)更有效。这项研究的长期目标是建立一个超声能量和通信平台，通过植入的传感和治疗设备实现对健康状况的非显眼的长期监测。非技术摘要：在过去的几十年里，糖尿病和肥胖症的患病率急剧上升。这些慢性疾病的主要并发症是心脏病、肾功能衰竭导致透析、视网膜病变导致失明，以及神经病变和血管功能不全导致截肢。无论是在金融方面还是在人类痛苦方面，这些都造成了巨大的损失。我们的研究直接解决了这个问题，开发了新技术，使长期植入式血糖监测仪不需要经皮线。该项目解决了植入式葡萄糖传感器技术现状的两个基本问题：缺乏合适的电源或电力传输机制，以及基于葡萄糖氧化酶的传感器寿命短且需要频繁重新校准。作为该项目的一部分，PI将创建一个超声波能量传输平台，允许葡萄糖传感器(或任何高度微型化的植入式生物传感器)直接由超声波能量供电。在非常小的尺寸和较大的植入深度下，通过人体组织的声能量传输从根本上比为植入的传感器供电的两种最常见的方法近场电磁(EM)或远场(RF)更有效。该项目将研究微尺度声换能器的设计和结构，使其能够实现比通过人体组织的EM或RF传输更高的功率密度。为了解决技术水平的第二个基本问题，PI将探索一种新的血糖传感方法，使用嵌入磁性颗粒的水凝胶。这种方法克服了困扰当前酶连续葡萄糖传感器的几个限制，还允许电子设备牢固地封装，因为电子传感元件不必与水凝胶直接接触。总而言之，这些进步有望极大地改进感知血糖的方法，并向任何高度微型化的植入式生物传感器供电。技术摘要：这项研究解决了限制植入式生物传感器，特别是血糖监测器潜力的两大挑战。第一种是以足够的密度传递能量，以实现极端的小型化。虽然仍然比射频或电磁能量传输更有效，但在非常小的范围内，由于最佳设备厚度、声波波长和组织中声波吸收的频率相关性之间的相互作用，标准超声波换能器很快就会开始失去效率。我们的指导性假设是，在这些小尺寸的情况下，替代的压电结构将更加有效。我们的工作将结合声传输模型、换能器设计和实验工作，以经验性地确定在非常小的规模下探测声发电极限的关键交互影响。其次，研究将解决葡萄糖传感器的一个重要问题，即它们的寿命严重有限，并且必须频繁重新校准，因为它们依赖于葡萄糖氧化酶和氧气的可用性来执行准确的测量。PI将探索一种新的方法，使用嵌入有排列的磁性颗粒的水凝胶来感知葡萄糖，而不是传统的电化学过程。这些功能化的水凝胶在葡萄糖存在下会膨胀。通过放置在水凝胶旁边的微型线圈的电感值的变化来感知膨胀。这种方法不仅克服了困扰当前酶连续葡萄糖传感器的几个限制，而且还允许电子设备牢固地封装，因为传感线圈不必与水凝胶直接接触。在毫米尺度的系统演示中，传感线圈将是多用途的，用于从植入物传回数据。总而言之，这项工作的三个不同方面可以为从根本上更小、更长寿命的植入传感器提供基础。

Proposal Title:Enabling Millimeter Scale Deeply Implanted Glucose Sensors through Ultrasonic Power Transfer and a Novel Glucose Sensing Mechanism Proposal Goal:The goal of the proposed project is to enable a new mode for power transfer to and communication with a deeply implanted intraluminal glucose monitor. The current state of the art in integrated circuit and MEMS sensing technologies enables cubic mm size implementations of complex systems for implanted sensors. However, such implementations are never actually realized because the necessary power and communications systems are too large. At very small sizes and large implantdepths acoustic energy transfer through human tissue is fundamentally more efficient than either near field electromagnetic (EM) or far field (RF). The long term goal of this research is to create an ultrasonic power and communications platform that will enable unobtrusive long term monitoring of health status through implanted sensing and therapeutic devices.Nontechnical Abstract: The past few decades have seen a dramatic increase in the prevalence of diabetes mellitus and obesity. The chief complications of these chronic diseases are cardiac disease, kidney failure leading to dialysis, retinopathy leading to blindness, and neuropathy and vascular insufficiency leading to amputations. These exert a huge toll, both in financial terms and in human suffering. Our research directly addresses this problem by developing new technologies that will enable long term implantable glucose monitors without the need for transcutaneous wires. This project addresses two fundamental problems with the current state of the art in implantable glucose sensors: lack of a suitable power supply or power transmission mechanism, and the short lifetime and frequent need for re-calibration of glucose oxidase based sensors. As part of this project, the PIs will create an ultrasonic power transmission platform that will allow the glucose sensor (or any highly miniaturized implantable bio-sensor) to be directly powered by ultrasonic energy. At very small sizes and large implant depths acoustic energy transfer through human tissue is fundamentally more efficient than either near field electromagnetic (EM) or far field (RF), the two most common methods of powering implanted sensors. This project will investigate micro-scale acoustic transducer designs and architectures that enable higher power density transmission than either EM or RF transmission through human tissue. To address the second fundamental problem with the state of the art, the PIs will explore a new glucose sensing method using hydrogels with embedded magnetic particles. This method overcomes several limitations that plague current enzymatic continuous glucose sensors and also allows the electronics to be robustly encapsulated as the electronic sensing element does not have to be in direct contact with the hydrogel. Together these advancements promise to enable a vastly improved method of sensing blood glucose and delivering power to any highly miniaturized implantable bio-sensor.Technical Abstract: This research addresses two major challenges that limit the potential of implanted biosensors in general, and glucose monitors in particular. The first is transferring energy at sufficient densities to enable extreme miniaturization. While still more efficient than RF or EM energy transfer, at very small scales, standard ultrasonic transducers rapidly start to lose efficiency due to the interplay between the optimal device thickness, acoustic wavelength, and the frequency dependence of acoustic absorption in tissue. Our guiding hypothesis is that alternative piezoelectric structures will be more efficient at these small sizes. Our work will couple acoustic transmission models, transducer design, and experimental work to empirically determine key interaction effects probing the limits of acoustic power generation at very small scales.Secondly, the research will address a significant issue with glucose sensors, namely that their lifetime is severely limited and they must be frequently re-calibrated because of their reliance on the availability glucose oxidase and oxygen to perform accurate measurements. The PIs will explore a new method using hydrogels with embedded aligned magnetic particles to sense glucose rather than the traditional electrochemical process. These functionalized hydrogels swell in the presence of glucose. The swelling is sensed through the change in inductance value of a miniature coil placed next to the hydrogel. This method not only overcomes several limitations that plague current enzymatic continuous glucose sensors but also allows the electronics to be robustly encapsulated as the sensing coil does not have to be in direct contact with the hydrogel. The sensing coil will be multi-purposed to send data back from the implant in a mm scale system demonstration. Taken together, the three different aspects of this work could provide a basis for fundamentally smaller, longer life implanted sensors.