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.

连续血糖监测 (CGM) 涉及重复测量生理葡萄糖浓度 密切监测并及时纠正糖尿病患者有问题的血糖模式 从而降低糖尿病相关并发症的风险，并最终实现闭环血液 血糖监测和胰岛素管理。使用电化学的市售 CGM 传感器 目前的方法受到准确性低等局限性的阻碍（尤其是在低血糖情况下） 浓度），稳定性差，滞后时间长。我们的目标是通过开发一个解决这些问题的方法 皮下植入式亲和微传感器，用于连续监测间质液中的葡萄糖。 该微传感器采用微机电系统 (MEMS) 技术创建，将具有小型化、 灵活的设计，可实现葡萄糖与合成生物相容性物质的亲和力结合的差异测量 水凝胶。亲和结合，其中葡萄糖特异性且可逆地结合到水凝胶上，而无需葡萄糖- 现有葡萄糖传感器中常见的消耗化学反应提供了高稳定性。 MEMS- 基于亲和力结合的差异测量能够快速、准确地测定葡萄糖 面对非特异性干扰时，尤其是在低血糖范围内的浓度。这些功能 以小型化、灵活的设计实现，最大限度地减少设备与组织相互作用的影响。 在设计中，微传感器位于柔性基板上，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。具有数百个有源感应区域 该设备尺寸为微米，通过小针植入腹部区域的皮肤下方。 在操作过程中，组织中的葡萄糖分子快速进入微传感器并与传感元件可逆地结合 水凝胶，其介电性能相应改变。同时，参考水凝胶的介电常数 属性仅在非特定干扰（例如温度）下发生变化。因此，微分介电常数 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用于经皮植入的差分亲和力微传感器 运行时间为 5-7 天，具有高度的稳定性和准确性。具体目标包括（1） 功能性水凝胶合成，(2) 器件设计和制造，以及 (3) 水凝胶和器件表征 体外和体内。该设备将来将进一步开发，以允许长期（数月或更长时间） 植入手术，并包含在人工胰腺中以实现闭环血糖控制。

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