A Differential Dielectric Affinity Microsensor for Stable and Accurate Glucose Mo

一种稳定、准确测量血糖的差分介电亲和微传感器

• 批准号: 8642995
• 负责人: Qiao Lin
• 金额: $ 110万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642995
• 关键词: Abdomen; Acute; Address; Adsorption; Adverse effects; Affinity; Animals; Artificial Pancreas; Behavior; Binding; Biocompatible; Biocompatible Materials; Biological Assay; Blood Glucose; Blood capillaries; Boronic Acids; Calibration; Complications of Diabetes Mellitus; Consumption; Detection; Device Designs; Device or Instrument Development; Devices; Diabetes Mellitus; Electrodes; Electronics; Encapsulated; Enzymes; Equilibrium; Foreign-Body Reaction; Future; Glucose; Goals; Gold; Hydrogels; Hypoglycemia; Implant; In Situ; In Vitro; Inflammatory; Insulin; Intercellular Fluid; Lead; Measurement; Measures; Mechanics; Membrane; Methods; Monitor; Needles; Patients; Pattern; Perforation; Physiological; Polymers; Population; Property; Proteins; Public Health; Reaction; Reaction Time; Resistance; Risk; Signal Transduction; Silicon; Skin; Solutions; Subcutaneous Tissue; Surface; System; Technology; Temperature; Testing; Time; Tissues; base; biomaterial compatibility; blood glucose regulation; capillary; chemical reaction; design; dielectric property; electric impedance; experience; flexibility; glucose monitor; glucose sensor; implantable device; implantation; implanted sensor; improved; in vitro testing; in vivo; innovation; miniaturize; minimally invasive; operation; parylene; public health relevance; receptor; response; sensor; surface coating

Continuous glucose monitoring (CGM) involves repetitive measurement of physiological glucose concentration to enable close monitoring and timely correction of problematic blood sugar patterns of patients with diabetes mellitus, thereby reducing the risk of diabetes-related complications and ultimately allowing closed-loop blood sugar monitoring and insulin administration. Commercially available CGM sensors that use electrochemical methods are currently hindered by limitations such as low accuracy (especially at hypoglycemic glucose concentrations), poor stability, and long lag times. We aim to address these issues by developing a subcutaneously implantable affinity microsensor for continuous monitoring of glucose in interstitial fluid. The microsensor, created using microelectromechanical systems (MEMS) technology, will have a miniaturized, flexible design to realize differential measurement of affinity binding of glucose to a synthetic, biocompatible hydrogel. Affinity binding, in which glucose binds specifically and reversibly to the hydrogel without glucose- consuming chemical reactions commonly found in existing glucose sensors, affords high stability. MEMS- based differential measurement of affinity binding enables rapid, accurate determination of glucose concentration, in particular in the hypoglycemic range, in the face of nonspecific disturbances. These functions are realized in a miniaturized, flexible design, which minimizes the effects of device-tissue interactions. In design, the microsensor resides on a flexible substrate and is integrated with a glucose-binding (sensing) hydrogel and a glucose-insensitive (reference) hydrogel. With an active sensing region hundreds of micrometers in size, the device is implanted (via a small needle) beneath the skin in the abdominal region. During operation, glucose molecules in tissue rapidly enter the microsensor and bind reversibly to the sensing hydrogel, whose dielectric properties change accordingly. Meanwhile, the reference hydrogel's dielectric properties change only with nonspecific disturbances (e.g., temperature). Thus, differential dielectric measurement allows accurate determination of the glucose concentration in the interstitial fluid. The direct goal of this project is to develop the differential affinity microsensor for percutaneously implanted operation over a period of 5-7 days with a high level of stability and accuracy. The specific aims include (1) functional hydrogel synthesis, (2) device design and fabrication, and (3) hydrogel and device characterization in vitro and in vivo. The device will in the future be further developed to allow long-term (months or longer) implanted operation, and be included in an artificial pancreas to enable closed-loop glucose control.

连续葡萄糖监测（CGM）涉及对生理葡萄糖浓度的重复测量 为了仔细监测并及时纠正糖尿病患者的血糖模式 Mellitus，从而降低了与糖尿病相关并发症的风险，并最终允许闭环血液 糖监测和胰岛素给药。使用电化学的市售CGM传感器 目前，方法受到诸如低精度之类的限制（尤其是在降血糖葡萄糖时）的限制 浓度），稳定性差和较长的滞后时间。我们旨在通过开发一个 皮下植入的亲和力微传感器，用于连续监测间质液中的葡萄糖。 使用微电动系统（MEMS）技术创建的微型传感器将具有微型化， 灵活设计，以实现葡萄糖与合成，生物相容性的亲和力结合的差异测量 水凝胶。亲和力结合，其中葡萄糖特异性地结合了无葡萄糖的水凝胶 在现有的葡萄糖传感器中通常发现的化学反应可提供高稳定性。 mems- 基于亲和力结合的基于差异测量可以快速，准确地确定葡萄糖 面对非特异性干扰，浓度，尤其是在降血糖范围内。这些功能 以微型，灵活的设计实现，从而最大程度地减少了设备组织相互作用的影响。 在设计中，微型传感器位于柔性底物上，并与葡萄糖结合（传感）集成 水凝胶和葡萄糖不敏感（参考）水凝胶。具有积极的感应区域数百个 尺寸的微米，该设备在腹部区域的皮肤下面植入（通过一根小针头）。 在操作过程中，组织中的葡萄糖分子迅速进入微传感器并可逆地与感应结合 水凝胶，其介电特性会发生相应的变化。同时，参考水凝胶的介电 性质仅随非特异性干扰（例如温度）而变化。因此，差分介电 测量可以准确测定间质液中的葡萄糖浓度。 该项目的直接目标是开发经皮植入的差异亲和力微传感器 在5-7天的时间内运行，具有高水平的稳定性和准确性。具体目的包括（1） 功能水凝胶合成，（2）设备设计和制造，以及（3）水凝胶和装置表征 体外和体内。将来将进一步开发该设备，以允许长期（几个月或更长时间） 植入的操作，并包括在人造胰腺中以实现闭环葡萄糖控制。

项目成果

A hydrogel-based glucose affinity microsensor.

• DOI: 10.1016/j.snb.2016.03.146
• 发表时间: 2016-12
• 期刊: SENSORS AND ACTUATORS B-CHEMICAL
• 影响因子: 8.4
• 作者: Shang, Junyi;Yan, Jing;Zhang, Zhixing;Huang, Xian;Maturavongsadit, Panita;Song, Bing;Jia, Yuan;Ma, Tieying;Li, Dachao;Xu, Kexin;Wang, Qian;Lin, Qiao
• 通讯作者: Lin, Qiao

A graphene-based affinity nanosensor for detection of low-charge and low-molecular-weight molecules.

• DOI: 10.1039/c5nr08866f
• 发表时间: 2016-03-21
• 期刊: Nanoscale
• 影响因子: 6.7
• 作者: Zhu Y;Hao Y;Adogla EA;Yan J;Li D;Xu K;Wang Q;Hone J;Lin Q
• 通讯作者: Lin Q