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）涉及重复测量生理葡萄糖浓度 能够密切监测和及时纠正糖尿病患者的有问题的血糖模式， 糖尿病，从而降低糖尿病相关并发症的风险，并最终允许闭环血液 血糖监测和胰岛素给药。使用电化学的市售CGM传感器 这些方法目前受到诸如低准确性（特别是在低血糖葡萄糖 浓度）、稳定性差和滞后时间长。我们的目标是通过制定一个 皮下植入亲和微传感器，用于连续监测组织液中的葡萄糖。 使用微机电系统（MEMS）技术创建的微传感器将具有小型化， 灵活的设计，以实现葡萄糖与合成的生物相容的 水凝胶。亲和结合，其中葡萄糖特异性地且可逆地结合至不含葡萄糖的水凝胶- 消耗现有葡萄糖传感器中常见的化学反应，提供高稳定性。MEMS- 基于亲和结合的差分测量能够快速、准确地测定葡萄糖 浓度，特别是在低血糖范围内，在面对非特异性干扰。这些功能 以小型化、灵活的设计实现，最大限度地减少了器械-组织相互作用的影响。 在设计中，微传感器驻留在柔性基板上，并与葡萄糖结合（传感） 水凝胶和葡萄糖不敏感（参比）水凝胶。有一个活跃的感应区， 该装置的尺寸为20微米，植入（通过一个小针头）腹部区域的皮肤下。 在操作过程中，组织中的葡萄糖分子迅速进入微传感器并与传感器可逆结合 水凝胶，其介电性质相应地改变。同时，参考水凝胶的电介质 特性仅随非特异性干扰而改变（例如，温度）。因此，差分电介质 测量允许精确确定间质液中的葡萄糖浓度。 本课题的直接目标是研制出一种用于生物植入的微分亲和微传感器 在5-7天的时间内运行，具有高水平的稳定性和准确性。具体目标包括：（1） 功能性水凝胶合成，（2）装置设计和制造，和（3）水凝胶和装置表征 在体外和体内。该设备将在未来进一步发展，以允许长期（数月或更长时间） 植入手术，并被包括在人工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