SCH: INT Wireless Implantable Electronic Biosensors for Tumor Monitoring

SCH：用于肿瘤监测的 INT 无线植入式电子生物传感器

• 批准号: 8897547
• 负责人: David Blaauw
• 金额: $ 46.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8897547
• 关键词: Acid-Base Equilibrium; Area; Biochemical; Biological Markers; Biopsy; Biosensor; Cancer Biology; Characteristics; Charge; Chemotherapy-Oncologic Procedure; Clinical; Development; Devices; Discipline; Disease; Education; Educational Curriculum; Electronics; Environment; Generations; Harvest; Healthcare; Image; Implant; Individual; Infrared Rays; Instruction; Intercellular Fluid; Life; Liquid substance; Malignant Neoplasms; Measures; Medical; Medical Research; Medicine; Metabolic; Methods; Monitor; Organ; Patients; Physiology; Positioning Attribute; Positron-Emission Tomography; Power Sources; Research Personnel; Solid Neoplasm; System; Technology; Time; Tissues; Treatment Failure; Wireless Technology; age group; cancer therapy; chemotherapy; design; extracellular; implantable device; improved; in vivo; interstitial; malignant breast neoplasm; meetings; mouse model; preclinical study; pressure; programs; response; seal; sensor; success; transmission process; treatment response; tumor; tumor metabolism; voltage

 DESCRIPTION (provided by applicant): Technologies to non-invasively, continuously measure biochemical, metabolic, and biophysical changes in living tissues and organs have the capability to transform medical research and health care. Imaging and biopsies currently are the predominant methods to analyze disease status. Since these approaches provide only a limited number of snapshots over extended periods of time, researchers and clinicians may miss critical changes in physiology and disease status. We propose to overcome this fundamental medical problem by developing a new generation of ultra-low power, wireless, implantable, mm- scale biosensors for real-time, continuous monitoring of interstitial fluid pressure or extracellular pH n tumors. Elevated interstitial fluid pressure and acidic pH are characteristic features of almost al solid tumors, and prior studies suggest that changes in these parameters may be sensitive, early biomarkers for treatment response in many different malignancies. We will design sensors for percutaneous insertion into a tumor before starting chemotherapy. Sensors will remain in place over the multi-week course of treatment, continuously recording pressure or extracellular pH for periodic wireless transmission to an external readout device. We expect changes in interstitial pressure or pH in tumors will occur before alterations in tumor size and at least as soon as changes in tumor metabolism measured by clinical positron emission tomography (PET) imaging. To meet the challenge of extended tumor monitoring, we will advance our biosensor technology in four new areas: 1) through-tissue energy harvesting of infrared (IR) radiation, which will enable implantable devices to operate essentially perpetually in a non-invasive manner; 2) a new self-starting voltage converter to allow system charging after encapsulation is completed, facilitating high quality sealing of the electronics from the in vivo environment; 3) new pressure sensing and pH readout circuits for stable readout under unregulated sensor power supplies; and 4) pre-clinical studies to determine response to therapy in a mouse model of breast cancer. The combined expertise of our multi-disciplinary team uniquely positions us to develop transformative new biosensor technology for continuous monitoring of tumor environments, which will advance understanding of cancer biology and ultimately improve personalized cancer therapy. RELEVANCE (See instructions): We will develop mm-scale electronic biosensors that can be implanted into a tumor to continuously monitor response to several weeks of cancer therapy. By measuring changes in fluid pressure or acid-base balance in a tumor, we expect to detect success or failure of treatment within days of beginning chemotherapy. We expect this biosensor technology ultimately will provide a cheaper, more accurate method to determine efficacy of cancer therapy, allowing doctors to tailor chemotherapy protocols to individual patients and increase patients cured of cancer.

 描述(由申请人提供)：非侵入性、连续测量活组织和器官中的生化、代谢和生物物理变化的技术有能力改变医学研究和卫生保健。目前，影像和活检是分析疾病状态的主要方法。由于这些方法在较长的时间内只提供有限数量的快照，研究人员和临床医生可能会错过生理和疾病状态的关键变化。我们建议通过开发新一代超低功耗、无线、可植入的毫米级生物传感器来克服这一根本医学问题，该传感器用于实时、连续地监测肿瘤的间质液体压力或细胞外pH。间质液体压力升高和酸性pH是几乎所有实体肿瘤的特征，先前的研究表明，这些参数的变化可能是许多不同恶性肿瘤治疗反应的敏感、早期生物标志物。在开始化疗之前，我们将设计用于经皮插入肿瘤的传感器。传感器将在为期数周的治疗过程中保持不变，连续记录压力或细胞外pH，以便定期无线传输到外部读数设备。我们预计肿瘤间质压力或pH值的改变将在肿瘤大小改变之前发生，至少在临床正电子发射断层扫描(PET)测量到的肿瘤代谢改变时发生。为了迎接扩展的肿瘤监测的挑战，我们将在四个新领域推进我们的生物传感器技术：1)通过组织收集红外线(IR)辐射的能量，这将使植入式设备能够基本上以非侵入性方式运行；2)新的自启动电压转换器，使系统在封装完成后能够充电，促进电子设备与体内环境的高质量密封；3)新的压力传感和pH读出电路，用于在不受调节的传感器电源下稳定地读出数据；4)临床前研究，以确定乳腺癌小鼠模型的治疗反应。我们的多学科团队的综合专业知识使我们能够开发变革性的新生物传感器技术，用于持续监测肿瘤环境，这将增进对癌症生物学的理解，并最终改进个性化癌症治疗。相关性(参见说明书)：我们将开发毫米级电子生物传感器，可以植入肿瘤中，持续监测几周癌症治疗的反应。通过测量肿瘤内液体压力或酸碱平衡的变化，我们希望在开始化疗的几天内检测治疗的成功或失败。我们预计，这种生物传感器技术最终将提供一种更便宜、更准确的方法来确定癌症治疗的疗效，使医生能够为个别患者量身定做化疗方案，并增加癌症治愈的患者。