A Chronically Implantable Microsensor Array for Monitoring Biomarkers Relevant to

用于监测相关生物标志物的长期植入式微传感器阵列

• 批准号: 7656638
• 负责人: Florian Solzbacher
• 金额: $ 20.46万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-12 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7656638
• 关键词: Acidosis; Acrylamides; Activities of Daily Living; Acute; Age; American; Americas; Area; Behavioral; Bicarbonates; Biocompatible; Biocompatible Coated Materials; Biological Markers; Biopsy; Blood; Blood Glucose; Carbohydrates; Carbon Dioxide; Computer Systems Development; Consumption; Custom; Data; Development; Diabetes Mellitus; Diet; Dietary Fats; Disease; Drops; Electronics; Energy Intake; Energy Metabolism; Environment; Epidemic; Equilibrium; Evaluation; Exercise; Fatty Acids; Fatty acid glycerol esters; Figs - dietary; Financial compensation; Future; Generations; Glucose; Glycogen; Goals; Hydrogels; Hypoglycemia; Implant; In Vitro; Individual; Investigation; Ketone Bodies; Ketoses; Ketosis; Life; Liver Glycogen; Measurement; Measures; Membrane; Metabolic; Metabolism; Minor; Monitor; Muscle; Obesity; Operative Surgical Procedures; Outpatients; Persons; Physiological; Plasma; Power Sources; Pressure Transducers; Procedures; Process; Reaction Time; Relative (related person); Research; Research Personnel; Rest; Sensitivity and Specificity; Signal Transduction; Silicones; Source; Staging; Study Section; Swelling; System; Techniques; Telemetry; Testing; United States National Institutes of Health; Utah; Weight maintenance regimen; Wireless Technology; Work; base; biomaterial compatibility; copolymer; cost; design; diabetic; diet and exercise; energy balance; falls; fatty acid oxidation; fighting; fitness; in vitro testing; parylene; pressure; prototype; respiratory; response; sensor; silicon carbide; small molecule; tool

DESCRIPTION (provided by applicant): Obesity is one of the most popular and growing diseases in America. Popular approaches to weight control such as exercise plans or low carbohydrate diets have failed to halt the American obesity epidemic. Obesity occurs when there is a persistent long-term excess in energy intake over energy expenditure, and will only be resolved when the individual makes behavioral changes that correct this energy imbalance. One reason that such behavioral changes fail to occur is that it is currently very difficult to monitor the effects of behavioral changes on the various components of energy balance under typical daily life conditions. Hence we propose the development of an implantable microsensor array that could be used to conveniently monitor biomarkers relevant to carbohydrate and fat utilization without interfering with daily life activities. Fats and carbohydrates are the body's two major sources of fuel, and their relative rates of utilization depend on factors such as age, diet, exercise intensity, and fitness level. The proposed sensor array could be used to continuously monitor systemic levels of glucose, pH, and pCO2/bicarbonate in the body both at rest and during exercise. We hypothesize that such a sensor will be sensitive enough to detect substantial increases (or decreases) in dietary fat consumption both on short term and also long term basis. In the proposed work we will develop, fabricate, and test an implantable sensor platform based on smart hydrogels and micromachined pressure sensors that would continuously measure glucose, pH, and CO2 with high long term stability and biocompatibility. The proposed equilibrium sensor array will consist of four hydrogels, in independent microcavities, that respond by swelling proportionally to the concentrations of glucose, CO2 and to the pH, the fourth hydrogel acts as a reference. The tendency of hydrogels to increase in volume in confined wells is captured by the pressure transducers. This project will be accomplished in three specific aims. The first one focuses on development and long term testing of hydrogels. Second specific aim focuses on developing the SiC platform and the third specific aim on biocompatibility coating tests and long term in vitro tests. This project will be conducted very diligently by the team of experts in the fields necessary to accomplish the goal. This project is designed to develop an implantable microsensor to continuously monitor the body's metabolism for a long term. A person may be implanted with such a sensor through a minor out patient surgery and it will not hinder the daily activities in anyway. Such a sensor would cost $30 to $50 and greatly benefit people fighting obesity and trying to restore energy balance.

描述（由申请人提供）：肥胖是美国最流行且日益严重的疾病之一。运动计划或低碳水化合物饮食等流行的体重控制方法未能阻止美国肥胖症的流行。当能量摄入持续长期超过能量消耗时，肥胖就会发生，并且只有当个人做出行为改变来纠正这种能量失衡时，肥胖才会得到解决。这种行为改变未能发生的原因之一是，目前很难在典型的日常生活条件下监测行为改变对能量平衡各个组成部分的影响。因此，我们建议开发一种可植入的微传感器阵列，可用于方便地监测与碳水化合物和脂肪利用相关的生物标志物，而不干扰日常生活活动。脂肪和碳水化合物是人体的两种主要燃料来源，它们的相对利用率取决于年龄、饮食、运动强度和健身水平等因素。所提出的传感器阵列可用于连续监测休息和运动期间体内葡萄糖、pH 值和 pCO2/碳酸氢盐的全身水平。我们假设这种传感器足够灵敏，可以检测短期和长期膳食脂肪消耗的大幅增加（或减少）。在拟议的工作中，我们将开发、制造和测试基于智能水凝胶和微机械压力传感器的植入式传感器平台，该平台将连续测量葡萄糖、pH 值和二氧化碳，具有高度的长期稳定性和生物相容性。所提出的平衡传感器阵列将由四个水凝胶组成，位于独立的微腔中，它们通过与葡萄糖、CO2 的浓度和 pH 值成比例地膨胀来响应，第四个水凝胶充当参考。压力传感器捕获水凝胶在有限井中体积增加的趋势。该项目将实现三个具体目标。第一个重点是水凝胶的开发和长期测试。第二个具体目标侧重于开发 SiC 平台，第三个具体目标侧重于生物相容性涂层测试和长期体外测试。该项目将由实现目标所需领域的专家团队非常努力地进行。 该项目旨在开发一种植入式微传感器，以长期持续监测人体的新陈代谢。一个人可以通过一个小型的门诊手术植入这样的传感器，并且无论如何都不会妨碍日常活动。这种传感器的成本为 30 至 50 美元，对于对抗肥胖和试图恢复能量平衡的人们来说将大有裨益。

项目成果

Development, Fabrication, and Characterization of Hydrogel Based Piezoresistive Pressure Sensors with Perforated Diaphragms.

• DOI: 10.1016/j.sna.2010.05.023
• 发表时间: 2010-06
• 期刊: SENSORS AND ACTUATORS A-PHYSICAL
• 影响因子: 4.6
• 作者: Orthner, M. P.;Buetefisch, Sebastian;Magda, J.;Rieth, L. W.;Solzbacher, F.
• 通讯作者: Solzbacher, F.

Hydrogel based sensor arrays (2 × 2) with perforated piezoresistive diaphragms for metabolic monitoring (in vitro).

• DOI: 10.1016/j.snb.2010.01.063
• 发表时间: 2010-03-19
• 期刊: SENSORS AND ACTUATORS B-CHEMICAL
• 影响因子: 8.4
• 作者: Orthner, M. P.;Lin, G.;Avula, M.;Buetefisch, S.;Magda, J.;Rieth, L. W.;Solzbacher, F.
• 通讯作者: Solzbacher, F.

Free swelling and confined smart hydrogels for applications in chemomechanical sensors for physiological monitoring.

• DOI: 10.1016/j.snb.2008.11.001
• 发表时间: 2009-02-02
• 期刊: SENSORS AND ACTUATORS B-CHEMICAL
• 影响因子: 8.4
• 作者: Lin, G.;Chang, S.;Kuo, C. -H.;Magda, J.;Solzbacher, F.
• 通讯作者: Solzbacher, F.

Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties.

• DOI: 10.1016/j.snb.2011.09.079
• 发表时间: 2011-12-15
• 期刊: SENSORS AND ACTUATORS B-CHEMICAL
• 影响因子: 8.4
• 作者: Horkay, F.;Cho, S. H.;Tathireddy, P.;Rieth, L.;Solzbacher, F.;Magda, J.
• 通讯作者: Magda, J.

Smart hydrogel based microsensing platform for continuous glucose monitoring.

基于智能水凝胶的微传感平台，用于连续血糖监测。

• DOI: 10.1109/iembs.2010.5626231
• 发表时间: 2010
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
• 作者: Tathireddy,Prashant;Avula,Mahender;Lin,Genyao;Cho,SeungHei;Guenther,Margarita;Schulz,Volker;Gerlach,Gerald;Magda,JulesJ;Solzbacher,Florian
• 通讯作者: Solzbacher,Florian