Implantable multi-analyte sensors for the continuous monitoring of body chemistri

描述(由申请人提供)：现有的医疗保健系统要求个人访问医疗保健机构进行时间点测试，以监控甚至最基本的健康状态标记物，这些标记物可能会遗漏对准确诊断至关重要的身体化学变化，特别是在高危人群中。连续的多分析健康传感器有可能极大地改变医疗保健，为分散医疗保健服务铺平道路，并将重点从反应性治疗转移到预防性维护。PROFUSA，Inc.建议通过开发由发光组织集成材料组成的高度微型化、可植入的多分析物传感器来改变当前的生物传感范式，以连续监测人体化学成分。开发植入式传感器的最大障碍是异物反应(FBR)。通过使用独特的组织集成支架，与目前的植入式传感器相比，这是一项重大的创新改进，因为它们诱导毛细血管形成和生长，而不是典型的FBR纤维包膜形成，从而实现了近距离接触代谢标志物和其他感兴趣的分析物。分析物特定的发光传感化学物质嵌入到这些水凝胶支架中。所产生的传感器被注射到皮下，并使用微型、无线、创可贴般的读取器进行光学监测，以进行连续测量，或使用手持棒进行定期自我测量，具体取决于临床需要。拟议的监测系统小得不明显，外形因素满足了患者广泛采用实时、长期监测身体化学物质的需求。此外，可以远程查看收集的数据，从而允许医生访问医疗数据，而无需患者在场，直到达到关键阈值。PROFUSA和合作者过去的努力已经成功地开发出了使用这项技术的葡萄糖传感器原型。在这里，提出了一种使用同一平台的多分析物连续监测仪的开发，并延长了寿命。由于葡萄糖和肌酐是食物摄入量、代谢和肾功能的重要标志，因此建议用它们来论证多分析物的概念。葡萄糖和肌酐传感纳米球将被单独开发和优化，并整合到组织集成支架中，以产生原型传感器。传感器的寿命和准确性将得到提高，以在体内实现所需的90天功能，最终目标是一年的功能。PROFUSA的多分析物传感器平台的开发可能会改变医疗保健，该平台有可能通过集成特定于感兴趣分析物的传感纳米球来定制各种疾病状态。临床上采用连续多角度传感器将使患者能够控制自己的健康，帮助他们做出维护健康的决定，同时使医生能够更准确地做出诊断和开出治疗处方。 与公共健康相关：我们的医疗保健系统要求个人访问医疗保健机构，以进行最基本的健康状况评估，这依赖于提供单一时间点快照的实验室测试，这可能会错过对正确诊断至关重要的波动。我们建议通过开发连续的、可植入的、长期的整体健康传感器来改变当前的医疗保健模式，这种传感器将为远程查看提供实时、连续的无线数据，减少医生就诊的频率，直到达到关键阈值。 采用PROFUSA的全面健康监测器将使患者能够为健康维护做出适当的决定，并通过访问历史数据，使医生能够做出更准确的诊断。

DESCRIPTION (provided by applicant): The existing health care system requires an individual to visit a health care facility to conduct point-in-time tests to monitor even the most basic healt status markers, which can miss fluctuations in body chemistries that are vital to accurate diagnoses, particularly in high-risk populations. Continuous multi-analyte health sensors have the potential to dramatically change health care by paving the way for decentralization of health care delivery and shifting the focus away from reactive treatment to preventative maintenance. PROFUSA, Inc. proposes to transform current biosensing paradigms by developing highly miniaturized, implantable, multi-analyte sensors composed of luminescent tissue integrating materials for continuous monitoring of body chemistries. The largest hurdle in developing implantable sensors is the foreign body response (FBR). Through the use of unique tissue integrating scaffolds, which are a major innovative improvement compared to current implantable sensors in that they induce capillary formation and in-growth rather than the typical FBR fibrous capsule formation, intimate access to metabolic markers and other analytes of interest is achieved. Analyte-specific luminescent sensing chemistries, are embedded in these hydrogel scaffolds. The resultant sensors are injected under the skin and monitored optically using a miniaturized, wireless, Band-Aid-like reader for continuous measurement or a hand-held wand for periodic self-measurement, depending on the clinical need. The proposed monitoring system is inconspicuously small and the form factor meets patient demands for widespread adoption of real-time, long-term monitoring body chemistries. Additionally, viewing of the collected data can be done remotely, allowing the physician access to medical data without the need for the patient to be present until a critical threshold is met. Past efforts by PROFUSA and collaborators have resulted in the successful development of prototype glucose sensors using this technology. Here, the development of a multi-analyte continuous monitor using the same platform is proposed with extended longevity. Glucose and creatinine are proposed to demonstrate the multi-analyte concept due to their importance as markers of food intake, metabolism and kidney function. Glucose and creatinine sensing nanospheres will be developed and optimized individually and incorporated into the tissue-integrating scaffolds to generate prototype sensors. Sensor longevity and accuracy will be enhanced to attain the desired 90-day functionality in vivo, with an ultimate goal of one year functionality. The development of PROFUSA's multi-analyte sensor platform, which has the potential for being customized to various disease states by integrating sensing nanospheres specific to analytes of interest, could potentially transform health care. Clinical adoption of a continuous multi-anlayte sensor will empower patients to take control of their own health, helping them to make decisions to maintain their health, while at the same time enabling physicians to more accurately reach a diagnosis and prescribe treatment. PUBLIC HEALTH RELEVANCE: Our health care system requires individuals to visit a health care facility for even the most basic health status evaluations, relying on lab tests that provide single point-in-time snapshot, which may miss fluctuations critical to proper diagnoses. We propose to shift current paradigms in healthcare through the development of continuous, implantable, long-term total health sensors, which will provide real-time, continuous wireless data for remote viewing, reducing frequency of doctor visits until a critical threshold is reached. Adoption of PROFUSA's total health monitor will empower patients to make the appropriate decisions for health maintenance and, by having access to historical data, will enable physicians to reach more accurate diagnoses.