EFRI-BioFlex: Hybrid polymer-paper based multi-sensor implants for continuous remote monitoring

脑积水是一种慢性无法治愈的疾病，其特征是脑脊液在大脑中过度积聚，每年每1000名新生儿中有1至2人患病。如今，治疗脑积水的主要方法是使用植入的分流器排出多余的液体，这种技术自20世纪50年代引入以来几乎没有改变。其暂时的疗效使脑积水成为神经外科中最常见的问题之一，患者一生中需要反复进行分流修复或更换。一个主要的未满足的需求是早期诊断分流故障，这是困难的，不可靠的，和昂贵的。智力优势：快速和准确的诊断对于及时干预和避免长期痛苦至关重要。因此，本提案的总体目标是实现一个变革性的无线操作多传感器系统，包括一个自我感知、自我报告的脑积水分流器。新概念将在材料，传感器，微加工和系统集成中引入，以克服当前的限制和工程挑战。柔性衬底将由选择性集成到聚合物载体膜中的纸组成，该载体膜可以直接应用于导管，也可以使用选择性图案和策略性放置的热敏生物粘合剂无缝连接到组织。具有新材料特性的复合薄膜衬底将包含传感器、电子设备和电源，同时仍然允许保形放置。功能引发的化学气相沉积聚合物将有选择地使用新技术来修饰表面，以减少免疫反应，防止生物污染和感染。电沉积薄膜将作为一种易于与BioFlex集成的新型传感器材料进行探索。多传感器阵列将具有？湿？电化学阻抗转导技术，不需要密封包装。对于符合标准柔性聚合物分流器且在体内占用有限空间的低轮廓多传感器系统来说，灵活性和微型外形因素至关重要。该系统为分流功能障碍的客观诊断和脑积水分流流体动力学的实时监测提供了一个无线技术平台，以实现更好的患者护理和治疗与疾病进展的相关性。在这里建立的基金会将促进BioFlex远程监测植入物在具有挑战性的重症监护应用中的长期发展。我们的技术团队在生物材料、表面涂层、建模和仿真、微电子、微机电系统制造和传感器、无线设备、可植入设备和系统集成方面具有互补优势，以实现生物电子植入物的转型。更广泛的影响：BioFlex将改善脑积水的护理，脑积水是一种慢性、不治之症，通常始于儿童时期，需要终生医疗护理。远程监测和及时干预将改善护理和生活质量，同时减少住院和医疗保健费用。开发和使用可植入的无线BioFlex治疗脑积水的经济和环境效益包括减少住院率、早期干预、预防危机管理、减少并发症和阻止疾病进展。这个平台将是未来自我意识发展的基础。多样化的BioFlex团队致力于扩大参与，并有广泛的记录来证明这一点。一个主要的重点是招聘不同的学生在所有教育水平的研究经验和重点指导。学生们将扩大作为BioFlex大使的影响力，为本科项目招募未来的工程师。国际合作将通过现有项目发展和丰富本科生、研究生和研究人员的交流。与儿科技术与创新中心和人体计算中心的合作将促进学生、研究人员、临床医生和行业之间的及时合作。

Hydrocephalus is a chronic incurable condition that characterized by the excess accumulation of cerebrospinal fluid in the brain and affects 1 to 2 in every 1000 births per year. Today, hydrocephalus is primarily treated using an implanted shunt to drain excess fluid, a technique that is virtually unchanged since its introduction in the 1950?s. Its temporary efficacy has made hydrocephalus one of the most frequently encountered problems in neurosurgery with repeated shunt revisions or replacements required over the lifetime of a patient. A major unmet need is early diagnosis of shunt malfunction which is difficult, unreliable, and costly. Intellectual Merit:Rapid and accurate diagnoses are critically important to initiate timely intervention and avoid prolonged suffering. Therefore, the overall goal of this proposal is to realize a transformative wirelessly-operated multi-sensor system comprising a self-aware, self-reporting hydrocephalus shunt. Novel concepts will be introduced in materials, sensors, microfabrication, and systems integration to overcome the current limitations and engineering challenges. Flexible substrates will consist of paper selectively integrated into a polymer carrier film that is either directly applied to catheters or seamlessly connected to tissue using selectively patterned and strategically placed thermosensitive bioadhesives. Composite thin film substrates with novel material properties will contain sensors, electronics, and a power source while still allowing conformal placement. Functional initiated chemical vapor deposited polymers will be selectively applied using novel techniques to modify surfaces to minimize immunologic responses and prevent biofouling and infection. Electrodeposited films will be explored as novel sensor materials that are easily integrated with BioFlex. Multi-sensor arrays will feature ?wet? electrochemical impedance transduction technology that does not requiring hermetic packaging. Flexibility and miniature form factor are critical for low profile multi-sensor systems that conform to standard flexible polymer shunts and occupy limited real estate in vivo. This system provides a wireless technology platform for the objective diagnosis of shunt dysfunction and real-time monitoring of hydrocephalus-shunt hydrodynamics to enable better patient care and correlation of treatment to disease progression. The foundation established here will promote long-term growth of BioFlex remote monitoring implants for challenging critical care applications. The technical team brings complementary strengths in biomaterials, surface coatings, modeling and simulation, microelectronics, microelectromechanical systems fabrication and sensors, wireless devices, implantable devices, and system integration to realize transformational bioelectronic implants. Broader Impacts:BioFlex will enable improved care of hydrocephalus, a chronic, incurable disease typically starting at childhood and requiring a lifetime of medical care. Remote monitoring followed by timely intervention will improve care and quality of life while reducing both hospitalizations and healthcare costs. The economic and environmental benefits of the development and use of implantable, wireless BioFlex for hydrocephalus include reduced hospital admissions, earlier interventions, prevention of crisis management, reduced complications, and halting of disease progression. This platform will be the basis for future development of self-aware . The diverse BioFlex team is committed to broadening participation with an extensive track record to prove it. A major focus is recruitment of diverse students for research experiences at all education levels and focused mentoring. Students will amplify outreach as BioFlex ambassadors to recruit future engineers to undergraduate programs. International collaborations will be developed and enriched through undergraduate, graduate, and researcher exchange through existing programs. Partnership with the Center for Technology and Innovation in Pediatrics and Center for Body Computing will promote timely collaboration between students, researchers, clinicians, and industry.